00:00:00BOHNING: What I'd like to do is go right back to the beginning. I know you were
born on New Year's Eve, 1921, in Brussels.
STORK: That's what they say. [laughter]
BOHNING: Could you tell me something about your parents and your family background?
STORK: Sure. I was born in Brussels, but we lived there for only about nine
months. My mother was French, from the Lorraine part of France, and my father's
family was from Brussels. But we lived in Paris afterwards, so I was brought up
BOHNING: What did your father do?
00:01:00STORK: My father was a jeweler. He and his three brothers inherited the business
of their father, who had a jewelry store. Actually, they had three of them. One
of them was in Brussels and one in Ostend, which is a summer resort. My father
was concerned with buying things, so they had an office in Paris, as far as I remember.
When he eventually came to this country he survived on extremely careful
handling of money that he had saved over the years, because he did not work here
again. I could presumably calculate how old he was when he showed up here. He
00:02:00was not that old; he probably was fifty, or some number like that. His older
brother was already in the States.
BOHNING: Why did he move to Paris?
STORK: I don't think my mother had any interest in living in Belgium. [laughter]
don't have all that great a reputation in Europe. The Belgians, to some western
Europeans, are sort of the Poles of Western Europe. That is, as you would expect
the Polish jokes in this country, the Belgian joke is a joke about someone who
is somewhat slower, and perhaps sort of dense. Especially in France, there are
likely to be Belgian jokes.
BOHNING: So you grew up in Paris. What was it like and what kind of schooling
did you have there?
00:03:00STORK: Elementary school is a very dim memory for me. I learned to read and
write, so far as I know, at home, probably mostly with my mother. I remember
vaguely that eventually I went to the lower school of the Lycée Janson de
Sailly. There are various lycées in France; they are essentially preparatory
schools for universities. It is a little bit like elementary school and high
school here; that is, at a certain point you switch over. So there was first
this lower school. Let's see, what would it be--ten, nine, eight? They count in
reverse there. Here you start with one and go up. There it's in reverse. You
00:04:00start with eleven, then ten, nine, eight, and so on and finally first.
In those days there was a terminal secondary school exam, a baccalauréat, which
was a two-part thing. You first had one, and then you had one more year where
you could divert to either mathematics or what they called philosophy, which, I
guess, would be the arts. Then you'd have another exam, the second part of your
so-called baccalauréat, which in France was essentially the entrance exam to
university. That is, if you pass this exam, you automatically could go to the
university. I don't know whether the system has changed, but I know that now
it's only one baccalauréat at the end.
So I was at the lycée called Janson de Sailly. These schools were extremely
good schools. They were just simply quite different, I'm sure, from what they
00:05:00are today, and very different from the American operation. The American
operation is essentially opposite to the European one; that is, you do
essentially nothing in the high school years, and then work very hard in
college. The French and probably Central European system was the reverse. You
killed yourself in high school, and then it was pppffffff. [laughter] It was
essentially nothing much. Which is why you could spend your time on the terrace
of a cafe with no great damage, once you got to college. But in high school, it
would be a rare day that you didn't have at least three hours of homework, and
weekends that you didn't spend memorizing history books, possibly without the
I have very mixed feelings about the European education system. There's no
00:06:00question that on paper it's infinitely superior. But there is serious doubt
about the extent to which one learns anything other than rote knowledge. That's
a different question, but it's not clear. It can be suspect: if you're taking
twelve subjects, there can be some suspicion about how much time you can devote
to understanding any one of them. But you do learn to survive the pain of
studying. That much you learn, that this is a normal sort of thing. You are
trained to do that, so then you don't mind it so much.
BOHNING: Were there any athletics?
STORK: Yes. Gym was compulsory. We had some of that. We ran around the
courtyard. I guess we probably played some volleyball and things like that.
BOHNING: But there were no organized sports of any kind?
00:07:00STORK: There were things you could join. There was an athletic association, but
it was nothing that was required. But drawing was required.
FINE: Tennis must have been required. [laughter]
STORK: No, no. [laughter] I was born in Paris and went to school there until
what would here be the ninth grade or tenth grade. The last three years, which
included both baccalauréats, were in the south of France in Nice, where I did
in fact play tennis, but that was just because it's nice weather. It's not a bad
thing to do, but that had nothing to do with the school.
00:08:00BOHNING: What was the science education like?
STORK: I remember a chemistry teacher--and in fact those who claim that there's
a relationship between teacher and eventual avocation may have a point. I
remember the chemistry teacher, but science education was mostly pretty
dogmatic, as it would have to be. You did two hours a week of physics and
chemistry, or whatever it was called. There was some sort of a lab where we did
awfully elementary things. Maybe we had a Bunsen burner and warmed up something,
although I don't really remember any details. This was in Nice, not in Paris. I
00:09:00don't remember anything about science education in Paris. I don't think there
was any experimental science there. There was, of course, mathematics.
But in Nice the personality of this chemistry teacher was quite different from
that of the other teachers. He was actually a very strong, no-nonsense person,
which was quite extraordinary. His class was probably the only one where I had a
certain amount of discipline. Discipline was a peculiar thing in the French
system. It was both brutally enforced and missing.
It became a point of honor to try to screw up the system because the system was
so tight. The penalty for twisting the cap of your fountain pen while the
00:10:00teacher was speaking was four hours of copying history books on the day off. The
days off in these days were not Saturday and Sunday, but Thursday and Sunday.
(This has now changed, I believe, to Saturday and Sunday.) So you spent Thursday
in there, copying pages. And if you accumulated enough of these penalty hours,
which I think was some number like thirty, in three months' time, then your
parents had to come and plead that you were not as bad as it appeared. So my
main aim was to keep it down to twenty. [laughter]
But it became essentially the system versus the individual. Presumably, all
these things have changed a lot. But this chemistry teacher was able to maintain
discipline in his classroom without resorting to such nonsense. To me, he was an
impressive person when you listened to him. I'm sure that made some sort of
00:11:00impression on me. I really didn't take serious chemistry until I came to this
country, when I entered the University of Florida, in February 1940.
BOHNING: At the time you had taken the chemistry, you hadn't given any thought
to making it a career.
STORK: Well, it was sort of by default. I mean, I was limited by how I had
studied English. I had studied English in high school, as a required subject. It
was required to study either English or German. So I studied English, which was
a couple of hours a week. You covered two pages of some Shakespeare play in
about a semester's time, and you dissected the hell out of it; you really didn't
00:12:00have very much of anything useful. But the French were very strong, both in
English and in French, in what they call explication de texte, which is the
dissection of everything there is to know about the sentence structure, how the
words relate to something, and so on. So you really didn't learn to speak that
much. When I came here, it took me a long time to understand what people were
talking about. I could write some English, and I could actually understand it to
a considerable extent if it was written. But it was several years before I could
understand what was going on in a movie. I could see the things moving around,
but I didn't understand the dialog in a movie. I didn't know what was going on.
The truth is, when you don't know a language it's easy for people to say, "Well,
00:13:00you can learn it." It's obviously true. At one extreme, you say, "If one billion
little Chinese can learn Chinese it mustn't be that hard." That's one point of
view. On the other hand, you're not convinced if you can't speak Chinese that,
in fact, it's something that you can learn. So that eliminated things like law
and business, that sort of thing, where you'd have to talk to people. Something
in which you would presumably deal with inanimate matter sounded very
So it was sort of by elimination. Actually, I've wondered about it once in a
while, "Why did I do that?" Well, when everything else sounded really pretty
00:14:00uninteresting, chemistry was interesting. I still remember exactly the day,
because it was sort of a revelation. Because of the language problem, because I
really did not relate to the American adolescent culture at that time, I was
really quite isolated. What did I do socially? Socially, I mostly stuck myself
in the library and looked around it. In those days, the library at the
University of Florida was about half the size of this room, and it had very
little of anything. But it was nice because there was essentially no one in
there when there was a football game going on.
Then, for some reason, which I don't remember, I had become interested in
quinine. This became a thread. A lot of psychological trauma came from that one
00:15:00thing--quinine. Why I became interested in quinine, I cannot imagine. But
whatever the reason was, I was looking around, and I was looking into quinine.
That probably was the second year that I was at the University of Florida. I was
there two and a half years, and the second year I was taking organic chemistry.
Maybe there was some formula of some alkaloids in the book that we used at the
time; I don't know what it was. Anyway, in Chemical Abstracts I came upon a
paper by Paul Rabe, a great German chemist who has more or less been ignored
since. Rabe had in fact done something that was
00:16:00unbelievable. That is, in the early 1930s, which was fifteen years before
anybody else did anything much on alkaloid structures, he had first of all found
out what the structure of quinine was, which is no mean feat, including,
eventually, its three-dimensional structure. He also had managed to synthesize
hydroquinine, which is the same thing as quinine except that it has an ethyl
group instead of a vinyl group, an accomplishment that was really quite amazing
for the time.
This was really attractive to me. You can see why, because I am not
mathematically inclined, I really doubted I could pass, even with effort, some
sort of elementary mathematics test. I had calculus and did quite well. But the
00:17:00fact is, I was not mathematical. Now chemical synthesis was something, which was
not mathematical at all. There's absolutely no mathematics in synthetic organic
chemistry; it's fantastic, whatever the science people say with respect to the
mathematical basis of science. There's a lot of science, which still has
absolutely nothing to do with it. Well, it may have something to do with
mathematics. If you say the world would not exist except in mathematical terms,
that's possible, for all I know. But that's a different thing. When I drive my
car there's a lot of mathematics involved there, but I'm not doing it. And in
organic chemistry, in synthesis at least, you don't really have mathematics at
the operational level. So that was quite attractive. It was something I could
actually follow and understand and get excited about. Also, there's the art part
of it, which is really a very nice feature. Now, why society tolerates it is
00:18:00something else. [laughter] But so long as society does, it is really quite nice.
At that time the question of whether society tolerated it didn't come up. It's
more of a problem now.
So I became extremely interested in organic synthesis and decided I should
synthesize quinine itself, the substance with the vinyl group. At that time I
became more and more interested in it. You don't know why you start collecting
stamps, but some people get fascinated by that, or playing chess, or whatever.
There's an initial event, and then you get caught up by this and it excludes
other things; the other things don't get a fair chance. If somebody had shown me
what oceanography was all about, maybe I would have liked that, I don't know. So
it happened that way.
BOHNING: I'd like to back up if I could and go back to Europe. I wanted to ask
you why your family came to the United States. Of course, the war and the
00:19:00political situation was pretty grim at that time. Was it 1939 when you came? Why
did they come here then, rather than some other country?
STORK: Well, what other country? People go to the United States because the
United States represented, and still does represent, freedom. That was one
reason for it. Another reason is that the older brother of my father was already
here at the time. He had been here for maybe a couple of years. I have no doubt
he was motivated by events in Europe. So there was somebody here. But then
again, the fundamental thing was that the United States was the United States.
America was freedom at that time, and probably still is.
00:20:00BOHNING: You had just finished the second baccalauréat.
STORK: That's right. I passed it in Nice, in the south of France. The
baccalauréat is a uniform degree, a uniform exam, all over France. That is, the
exams are sent from Paris to the various parts, all opened simultaneously, and
everybody took the exam at the same time. A crazy French operation. When that
was finished, my parents came and, obviously, I came with them. And that's it.
BOHNING: Frances Hoffman has a number of your childhood stories in the Aldrich article.
STORK: Yes, I brought this along just in case I needed to refer to it.
[laughter] I actually was conned into reading this thing and correcting some of
it, and on the whole this is pretty much true, what's in there.
BOHNING: Do you have any other memories of growing up in Paris, unrelated to
00:21:00schoolwork? What it was like growing up there, as a young boy?
STORK: It was highly structured. You walked to school (Janson de Sailly) which
was about a mile from where we lived in an apartment in Paris. You walked there
early in the morning (sometimes it was dark when you left) and came back home
for lunch, which was interesting.
There was a couple hours' break for lunch and then you had to come back to
school. Come back home in the evening, do your homework, go to sleep, go back
there. Go there on Thursday to copy pages out of a history book. [laughter] And
on Sunday, French society (and I suspect Indian society must be that way even
more so) was extremely structured in the sense that there was really not much
00:22:00intergroup visiting. The idea of dropping in on some friends to play checkers or
whatever wasn't done by most people of that particular social group. You didn't
do that; you just went home. Even the telephone was not something that you
really used. We really didn't do very much socially.
There was one time when I transgressed that sort of thing. A friend of mine had
a bicycle, and I wasn't allowed to ride my bicycle in Paris. But we would race
against the clock on his bicycle; we'd just go up to a point, come back, and
00:23:00clock it. That was not good, especially when I was knocked over by a taxicab. I
couldn't hide the fact that I was out there bicycling because the police brought
me home kind of bloody. This was bad. The reaction was clearly an emotional one,
but there was also considerable unhappiness when they heard that I was racing
around on a bicycle. There were a great many reasons for my parents' concern,
including the fact that this was not something we "did."
I still remember one time when we were playing in the schoolyard, at a place
where you could play sort of handball. I don't think people play that here. It's
with a leather ball, about that big, and you hit it against some sort of a wall
and it has to hit the wall above a certain point. It doesn't bounce much; it
only bounces about that much. I don't think that's what American handball is,
because handball is a bouncing ball that bounces a lot; this doesn't bounce
much. But we were playing happily enough when school was over. Maybe school was
00:24:00over at 5:00 p.m., so it was 5:15 or something like that; there was nobody there
at the time. The head of the school ran into us and was indignant, and was going
to tell our parents. [laughter] It was simply just not part of the structure. I
had four hours punishment once for being in a classroom reading a book instead
of being outside, during recess, kicking balls when you were supposed to be
kicking balls. It cost me four hours because of it. [laughter]
Life was highly structured in a peculiar way, so that there was not all that
much social interaction. Interaction was with family on Sundays. We had a house
about six miles outside of Paris, where eventually we moved to from the Paris
apartment and lived there, in a place called Garches. On Sunday, the Paris
00:25:00family would come out there, eat cookies and who knows what, play croquet. [laughter]
Here is another example from which you can get an idea of the structure of this
stratified society. I had a bicycle when we moved to Garches. I was allowed to
go around Garches with my bicycle and do various things with it. The French are
very high on cycling. It's the national sport; there's the Tour de France and
things like that. So I had visions of becoming a cycling champion of some sort,
even though my bicycle was an extremely heavy toy bicycle. There was a race
every year in Garches in which you went around the town x times and then
00:26:00somebody eventually won. And I did whatever it is that one has to do to enter
that race! I had no time to get from the place where you registered, which was I
think the plumbing supply place, to my house before my parents had been
contacted by the plumber who thought that they should know that their son was
thinking of entering. This was considered definitely a working class sort of
event. The funny thing was that it was this plumber, who was part of the working
class, who alerted them to the fact that there was something bizarre there.
[laughter] He was a strange character. So there was not all that much
interaction other than with family, and sort of in school, to the extent that
you had to be involved with school.
BOHNING: I was going to ask about your family. Do you have any brothers and sisters?
00:27:00STORK: I have a sister who lives in the south of France in Carcassonne. She's
five years younger than I am. We eventually became quite close when she was
probably in her late forties, after she lost her husband. Before that, we
considered each other only a nuisance. [laughter] She taught English in a French
I had a brother who was younger; there was about a year and a half difference
between the two of us. He died when I was five or six. This affected my mother
very much. This was in the days before antibiotics; he had a middle ear
infection and died. My mother always believed that the doctor was clearly
00:28:00responsible. The good part of this was that she had absolutely no use for
doctors, which probably saved the lives of several of her relatives, and beyond
that had no particular awe of them. The idea of second opinion must have
originated with my mother from that event. [laughter] The other thing is that
she had great ups and downs in mood, which also contributed to my being even
more set apart from society than the normal French system would do, because her
moods were sort of inexplicable to me as a young child. So the only thing was to
00:29:00withdraw from this. My father was a sort of a mythical figure. I had enormous
respect for my father, but we had almost no contact. I knew my father, I saw my
father, I loved my father; so far as I knew he loved me, but he was really very
much dominated by my mother, except in important decisions. He really made
important decisions, such as coming to this country, which was a very major
decision in the context of Europe back then. She would go along with that. But
the day-to-day tornado was under her control. [laughter]
[END OF TAPE, SIDE 1]
STORK: That continued after she was in this country. She was a very remarkable
00:30:00person. She could be absolutely charming, and absolutely incomprehensible. Very,
BOHNING: It sounds like you did a lot of reading.
BOHNING: What types of things did you read?
STORK: Mostly chemistry things having to do with synthesis.
BOHNING: But I meant other than chemistry.
STORK: Not that much. Literary reading I did under forced conditions; that's
actually quite an interesting thing. I would guess that ninety-eight percent of
the population in this country of any educational level reads more than I do of
any of the things that normal educated people read, such as novels or even
detective stories. I was lucky with detective stories. The first and probably
next to last detective story I ever read was Murder on the Orient Express by
00:31:00Agatha Christie, which is really not bad. I really didn't read all that much.
When I came here, it was at the time that you probably would read the most, but
the language was a problem. I had to be made to read. I took one course that was
required, some sort of elementary English, whatever they called it. I had to
read something about Queen Victoria. I forget what else. I had to read various
things like that. So I read that, but it was slow. Mostly I would read maybe a
couple pages in the beginning, a couple pages in the middle, and a couple pages
at the end. I was sometimes fascinated by how they end these things and how they
start them. But I don't really get that much about the story itself. So I really
00:32:00don't read all that much of anything. Some historical things I read.
BOHNING: What about when you were younger in France?
STORK: Yes, then I did. At that time I was very much interested in poetry. I
spent time putting what I considered to be poetry on paper. I can't say that I
wrote poetry because that's much too exalted for what I did. But that was
actually a fairly serious effort. I can just say that this was part of the
normal growing turmoil. To a large part, it was, especially as a fair number of
these poems were dedicated to girls even younger than I. But I cared about it
and I knew a fair amount about it.
00:33:00I was actually quite good in French literature. I had a feel for French writing
at that time, enough so that I even represented my school: in secondary schools
they selected three people to represent the school in a national competition. I
did not win anything. But nevertheless, that was something that I cared about.
French books are actually marvelous. I never understood the English language
literature with respect to the number of words that people use to tell you
something. It's really incredible compared to the French. The French novel is a
flimsy two hundred and thirty little pages like that with large character, which
you can easily read on the train from Paris to Le Mans, which is less than a
two-hour ride. I think it's just great. My feeling has always been that if you
can't say what you want to say in that many pages, you probably don't know what
00:34:00you want to say. It's really quite bothersome; it takes too much time. Even
after I was in this country I would read French novels once in a while, mostly
for that reason. It was the standard sort of thing that you would read--[Jean
Paul] Sartre, [Albert] Camus; that sort of thing.
Or they would be historical things. The person that is nominally in charge of
the film department here (whose name I forget at the moment) is a very
well-known movie writer (Amadeus) who should do a movie of my favorite
historical figure. He definitely must make a movie of [Pierre Augustin]
Beaumarchais. Beaumarchais was a fantastic figure. There is a boulevard in Paris
00:35:00called Boulevard Beaumarchais, so somebody would recognize it. Everybody knows
Beaumarchais because he wrote the libretto for The Marriage of Figaro. Most
people don't realize it, but you can actually make a case that the American
Revolution might not have succeeded were it not for Beaumarchais. Which is a
remarkable statement, and I'll let it go at that. But let's say that figure,
which is really not that well-known, started life making the thinnest watch that
had ever been made. He was a watchmaker. The thinnest watch in the world, which
brought him to the attention of the court, and that started an unbelievable
career, which included supplying the American Revolution with arms under some
00:36:00Spanish false name. It was really quite a fantastic operation. Things like that,
I like. But they're short--fascinating, but short. I don't care for books like
Gone With the Wind or things like that. [laughter] Some of it I just plain don't
understand. Some of it I've tried to read, but often it's just trivial. I'm not
reading that much science either anymore, except current stuff that you need to
read, like the journals.
BOHNING: When you came to this country in 1939, how long did it take before you
decided you wanted to go to a higher educational program here?
00:37:00STORK: I don't think it ever was a thought. That was something that I was
obviously going to do, without any thought being given to it. I mean, you did
that. In those days, the people who were in our particular social group knew
about the lycées (secondary school), (there was another parallel system which
you had a sort of dim awareness of, some sort of vocational school system). And
these people went to the lycées, which terminated in the baccalauréat. If you
passed the baccalauréat, that almost made it sure that you would go to a
university simply because why else would you want to follow that course? The
system said: now you can go to the university. So you just did that.
00:38:00So I don't think I ever gave it a thought. Then, eventually, I became fascinated
by this quinine business. I had my own lab at the University of Florida when I
was there for about two and a half years. There was nobody there. (Actually,
it's a very good place today.) It was really a very peculiar place, but I had my
own lab and I could do what I wanted. I could easily have killed myself; there's
no question about that.
BOHNING: The story by Frances Hoffman tells how you got to the University of
Florida. You had intended to go to UNC [University of North Carolina] originally.
STORK: Yes, this actually is quite right because I told her that. When we came
here, I didn't know anything. The first thing I wanted to find out was about the
universities. I was extremely withdrawn and I couldn't speak English very well.
So what do you do? You go to the library. The library is one thing that I
00:39:00understood. So I went to The New York Public Library. I spent most every day in
The New York Public Library. I haven't been there since. [laughter] That's not
true; I was once there to try to find a patent. I think it's almost impossible
to find a patent at The New York Public Library.
FINE: Did you come into Ellis Island?
STORK: No. I think even in those days Ellis Island didn't function anymore. I
don't know when they stopped.
So I just studied the books relating to U.S. educational operation and
eventually got some fantastic conclusions out of this. There were some
requirements that were pretty serious. I was aware that money was going to be a
problem and so, obviously, I wasn't going to go to a place where I had to pay.
Now, in the European system you essentially didn't pay anything in those days.
You paid maybe twenty dollars a year to register, or something like that. It's
probably changed, but not much. It's more like the New York City system. So it
00:40:00obviously had to be a non-private institution. I thought the possibility of a
fellowship or scholarship was null. But I did check schools here because we were
in New York. I stopped somewhere within the confines of Low Library, at
Columbia, where they made it clear that they would never in a million years
consider my application. [laughter] But I didn't go any further because I'm not
sure I understood; there was a nice gray-haired lady who I talked to. Then I
went to the New York Public Library, researched these things, and concluded that
North Carolina was where I should go.
BOHNING: Why did you conclude that North Carolina was the place?
STORK: It just came out of these damn pamphlets from the U.S. Office of
Education. They had tables showing what fields they were very good in; they
indicated that chemistry was one of them at North Columbia. And you didn't have
to pay anything--it was free; et cetera, et cetera. And it was reasonable
timing, because it sounded to me that it was less cold in North Carolina than
00:41:00here in New York. You have to remember that before that I was in the south of
France in Nice, where I could play tennis every day.
So then I was on my way to North Carolina. It turned out they had a quarter
system, which meant I was too early for one and too late for another. I think
the story that Frances Hoffman wrote is slightly exaggerated. It was not quite
that I stayed on the bus until it became warm enough that I thought it
worthwhile and got off. [laughter] I'm not sure whether that's what she said,
BOHNING: It's close.
STORK: No, it's more of a caricature of reality. What happened is that I'd
looked at it and thought North Carolina, but then it turned out it didn't seem
suitable to me. Then I said, "Well, what else is near there?" and it turned out
00:42:00to be the University of Florida, so then I went there. By that time my parents
had decided to settle in St. Petersburg, Florida. That was another good reason.
I really don't know why they moved there. Probably there was some motivation
that it was not too expensive to live, and it was warmer than New York. Or,
maybe, there was somebody whom they met or whom they knew who lived there. When
I got to St. Petersburg, I said, "Well, what universities are around here?" It
turned out to be the University of Florida.
In February of 1940, I entered the University of Florida. I got some advanced
standing of a very bizarre nature. I didn't care what credits they gave me, but
00:43:00the extraordinary thing was that they gave me three credits for French but
twelve for Greek, which was fabulous and difficult to explain, but unimportant.
[laughter] I had taken what the French call Greek for four years. Classical
Greek. I can read the signs on sorority houses, and that's about it. [laughter]
But nevertheless I had four years of Greek. I can read it; I can read it without
understanding it. I can read it about as fast as I can read French. Noise-wise,
with the sound of it, there's no problem. But the fact is that I don't know what
it means. And I got twelve credits out of it.
The net result of it is that I could get out of there in two and a half years,
especially because the chemistry course was not divisible. If you entered in
February, you had to take the final exam for the whole year. This was a good
thing, which almost cost me my first year. (I don't know whether Hoffman goes
into this or not.) I was doing very well on the chemistry exams, which were a
00:44:00multiple choice thing, where I could test my hypothesis that the longest answer
is statistically much more likely to be the correct one than the shortest one
simply because it's harder to phrase correct things than incorrect things. I'm
not sure if it's still true. I
wouldn't be surprised, but it probably has been adjusted by this time. Possibly
for that reason I was doing extremely well on these tests.
But I never went to the lab. I went to check out the equipment. I thought that
you went to the lab if you didn't know the answer to the question and then you
tried to find out. But I knew the answers to these questions, so I thought I
didn't have to go to the lab. I never went. The next time I went was to check
00:45:00in. I remember there was a little porcelain spatula that had a little cup at one
end and a little flat thing at the other end. It's about that long [three
inches]. There was a slight chip on the flat part; they charged me twenty cents
or something for it. I was outraged; I'd never been there! I'd never touched the
thing! [laughter] It turned out that it was serious because although I got very
good grades on the tests, no one had ever mentioned I was supposed to go to that
lab. So they flunked me, because I didn't go to the lab. I learned afterwards
that, once in a while, they would give tests in that lab, and I was never there.
But they never said anything about it!
That was pretty serious. I thought it was very serious because you had to pay.
They had a system, which was an interesting system. Although the school was
free, if you flunked the course you had to pay sixteen dollars. That was the
time when a hamburger was ten cents and a Coke was five cents. That's like one
00:46:00hundred or two hundred bucks today. Two hundred dollars is a lot of money to
pay. So that was much more serious so far as I was concerned, than the fact that
I'd gotten an "incomplete." But an incomplete would have been murder because I
would have wasted a year; I would have to take this damn thing over again. So I
carefully studied the rules and regulations of the university and found out that
if somebody is not doing satisfactorily, he has to be told. And if he pays no
attention then he has to receive some sort of a letter. But I had never received
anything. So I raised all hell about it, that I didn't want to pay that sixteen
dollars. Eventually they compromised and gave me a C for the year. But that C
was okay because that's passing. [laughter]
So then I could go on to the next thing, which was organic. I took organic
chemistry and I passed my physical chemistry. I was very lucky because I think
00:47:00it was the end of the old, essentially non-mathematical physical chemistry. I
think the textbook was by Farrington Daniels.
BOHNING: What about organic? Do you remember what you used for organic?
STORK: It was a big red book and the last name started with a W. I could find
out easily enough. At the moment I don't remember and I don't have that book
anymore. It had photographs every so often of people like Emil Fischer and other
well-known organic chemists.
FINE: Was it Frank Whitmore?
STORK: No, Whitmore was a serious sort of thing that I got later. The other text
00:48:00was the College Outline Series, which in those days was only that size [four
inches in length] (now it's expanded to be eight inches in length) and had some
nutshells of things which our chemistry professor was very fond of. His name was
Cash Blair Pollard. He was very fond of it because he was one of the editors. We
had to buy this book, and he presumably got some sort of royalty out of it. So
that was one book that we had.
He didn't know much organic chemistry. I think maybe it's mentioned in here, but
I'm not sure. The main thing that I knew about him was that he was a former
baseball coach at Purdue, and other than that, he raised police dogs. He was on
good terms with the Gainesville police. There was one graduate student who was
00:49:00given to extracurricular activities of various types. Pollard always knew what
he had been up to because he would get these reports from the police. [laughter]
They were fairly innocuous sort of things, but rather colorful. But Pollard
really didn't know very much about chemistry, and this was probably a very good
thing, because then I could fool around. He probably had no idea what quinine
was in the first place.
BOHNING: Who was chairman of the department and how many people were in the department?
STORK: There were four professors. There was one general chemistry teacher who
knew strictly nothing, and lectured on general chemistry. In those days, general
chemistry was extremely different from what it is today. General chemistry today
is essentially physical chemistry, so far as I can see, and physical chemistry
in the modern sense, not in the sense that I had it. [laughter] General
00:50:00chemistry was descriptive chemistry, so you did in fact learn the famous quote
that "Silver chloride is not a green gas." But you
didn't really learn much of anything else. That person taught it, and it was a
full-time job; I guess he was in charge of the general chemistry labs as well,
which I didn't go to. The organic person was Pollard.
There was a physical chemistry professor, [John Erskine] Hawkins, who was a very
nice man. I owe a lot to Hawkins, because I had decided I was going to stay at
Florida. I had my lab and I was perfectly happy getting my Ph.D. there. All I
had to do was continue doing things in the lab, and obviously I could make
quinine within the next few weeks. [laughter] I could do that and get my Ph.D.
What's wrong with that? Hawkins convinced me that I was out of my mind, and that
00:51:00I should go to a "decent" place, which he made perfectly clear he didn't think
Florida was. But he was a very nice man. I still remember he had a place with
high ceilings and there were distillation columns that went all the way up. They
were filled with different kinds of things. He worked with turpentine, which was
a great thing in Florida. There were pots full of turpentine, and he distilled
and fractionated them and measured the efficiency of these columns. This is
where I learned what an H.E.T.P. is, which is the height equivalent to a
theoretical plate, which measures the efficiency of these columns. This is about
as far as physical chemistry could go; not quite, but pretty much so. The
physical chemistry lab there was a reasonably serious lab. We did things; we
00:52:00tested things. I don't remember what it was, but we did and Hawkins oversaw
them; he was himself in the lab. He was a pretty good teacher. I managed to get
the highest grade in part of that course, at one time. But that is obviously a
reflection on the technique of teaching, because I don't know the slightest
thing about it. You could do a fair amount by memorizing. Anyway, he was a fine person.
And there was a fourth person who taught analytical chemistry. He was
commissioner of public works in Gainesville. He was a very fine person. We did
some electrochemistry experiments, plating copper on double platinum cylinders
that were rotating some way or another, and finding out something about the
00:53:00current that was passing through. His main interest was the rate of growth of
things that eventually plug up pipes. It was actually quite amazing. I don't
know if you've ever seen a pipe that carries hard water or whatever; they get
filled up with this solid chunk until eventually there's only that much of a
hole left. That was really what he was very much interested in; he was a fine
person. His name was [Alvin Percy] Black. Those were the four people that made
up the chemistry department of the University of Florida.
BOHNING: Was it all-male at that time?
STORK: Yes. At that time it was roughly three thousand students. There was an
00:54:00agricultural experiment station. Blacks were not allowed in. It was the real
South at the time. It was something that seemed sort of puzzling, so far as I
was concerned, because that was something I did not know. In the summer, there
were women, maybe schoolteachers, who would be there in the summertime. I became
aware of this because I had a job as a waiter in a private establishment just
outside of the college. In the summer, there was a lot of business there. I
didn't understand English well enough. I remember when somebody in a crowded
room full of these schoolteachers ordered what was probably beer of some kind
00:55:00and I thought they wanted watermelon. [laughter] I made my way with this big
watermelon through this crowded room, and it was not the right thing. Eventually
I got fired from that job. I actually got paid in meals; I got no cash for this.
I got five dollars' worth of meal tickets per week. But five dollars was pretty
good, because it was blue-plate specials, which were these plates where they had
two vegetables and some meat. The blue-plate special was only twenty-five cents,
which was not bad. We got paid that way. And then you could go back into the
room where they stored stuff and steal some food here and there. [laughter] On
the whole, Florida was not an unpleasant experience.
BOHNING: Who gave you the laboratory to work in on your own?
00:56:00STORK: Well, there was space and it just happened. I'm reconstructing. I
probably must have asked Pollard if it was all right. My dim recollection was
that there was a person getting a Ph.D. working in that lab. I think his last
name was Sugar, something like that. He was getting a Ph.D. making various
piperazines. Pollard's research interest was making piperazines. You may or may
not know that piperazine was not one of the most interesting compounds that
people were interested in. It's a reduced pyridine with another nitrogen
diametrically opposite the first nitrogen. It is a reduced thing. This chemistry
is minor, but you can make various substituted piperazines, and determine their
boiling points, refractive indices, things like that. [laughter] That was a big
00:57:00thing at that time; a UV instrument was not, in fact, anything that probably
anybody had except in physics. This guy was getting a Ph.D. at the University of
Florida and it may be that I started to talk to him. I remember that he had
space in the lab. There was space for another person easily in that place. So it
may be that this is how it started; I asked him if it was all right if I worked
there, and it was all right.
And there was a glassblower. I remember the glassblower had pellagra. Pellagra
is an unusual disease. You don't get pellagra easily; that's caused by a lack of
niacin, I think. This poor guy had pellagra, but then he recovered from pellagra
and had nothing much to do. So he was making instruments and whatever it is that
I wanted him to make. It was great. I didn't have to pay for chemicals; it was
really pretty good.
[END OF TAPE, SIDE 2]
00:58:00STORK: So I started making quinine there, but it took longer than I thought. I
actually started lecturing about quinine finally, for the first time, at the
[George] Büchi symposium only two years ago at MIT, when Büchi retired. (I
hope you're getting something from him because he certainly is somebody that you
must have on tape.) At the Büchi symposium I did talk about my fiddling around
with quinine, which was a nice sort of thing for that kind of an occasion.
The idea that I would make quinine as a thesis subject was an exaggeration. But
00:59:00I've learned the potentially useful but continually forgotten thing, which is
that in my particular case anything which I think will take a certain length of
time to do will in fact take seven times as long, if I'm lucky. Now there's an
important corollary of that. There are many projects I still have unfinished,
because there are many problems that I would start, or convince somebody to try,
on the grounds that it would only take a couple of weeks. "We can perfectly well
take care of it in that time." If I really were convinced that what I'm really
talking about is a minimum of fourteen weeks or whatever, I would probably
decide, "Well, I really don't want to spend that much time." In the case of
quinine it was even worse. I thought it would take three years, and it's taken
01:00:00more than twenty-one. In this case it's been more like forty. That's a long time.
BOHNING: Do you still have that original proposed synthesis that you worked out
STORK: I have this somewhat embarrassing document. I went to the University of
Wisconsin. The story Frances Hoffman tells about this is correct, that I was
really planning to go to Illinois. I didn't tell anybody that I was going to
Illinois. Again, it was quite a peculiar operation. I had a total lack of
knowledge of the American system, based on the underlying assumption that like
the European system it was a unified system. So you go wherever you care to go.
It makes no difference; it's all the same. Of course, that was not true, except
for the fact that various people work in various different areas. So I decided
Illinois was clearly the place because I was interested in quinine; quinine has
01:01:00a piperidine kind of ring system and I would work on that kind of structure.
Roger Adams at Illinois had done some alkaloid work, which embodied some
piperidine rings. There's more to quinine synthesis than that. I would be aware
of it today, but I wasn't at the time. Besides, Roger Adams was a very good
chemist. At that time, he was really the tops. So I would go there. But I also
knew about [Samuel L.] McElvain, who was doing a lot of work in pyridine
chemistry, which was conceptually totally irrelevant to what I was interested
in. It's like being interested in benzene versus monocyclic terpenes. It's not
the same; that is, they are both six-membered rings, but really quite different.
Aromatic substitution is not the same as making terpenes.
So the fact is that when I went to Wisconsin (or Illinois) I was prepared. I
assumed that if you were going to work on a Ph.D., you were supposed to do
01:02:00something original. Incidentally, the field of chemistry is a mysterious field.
It is mysterious in that it is a field in which the Ph.D. clearly has become a
strange operation in which the one thing you learn almost nothing about, except
in rare cases, is whether the person to whom you're awarding a Ph.D. is capable
of original work, which this degree is supposed to reward. At that time it
didn't even occur to me to question this; something original was what one had to do.
So I prepared some sort of project I gave to McElvain. I gave it to McElvain,
and McElvain was pretty startled. [laughter] So I had prepared it. The only
excuse you can give for that document is immaturity. It was really pretty bad.
01:03:00It was pretty bad. There was not even much thought there, at that point.
Eventually, it became better after I started graduate school; then I started
thinking. I actually refined my plan to some extent. I still have it. What was
missing from it, and which became clear within the first year that I was at
Wisconsin, was a feel for the problems of three dimensionality. That's a problem
that I had known about for a long time. The main event between 1942 and 1950,
and I don't mean just in this country but worldwide, was the sudden
01:04:00consciousness that most organic natural products were not flat projections.
People knew this as intellectual knowledge, but they did not feel it. One
essentially ignored it.
But my quinine involvement is really quite something. It's somewhat typical of
everything that's wrong with what I do and what has motivated me. What's wrong
with it is the inability to give up something to which I'm emotionally attached.
If it had been any kind of business decision, subject to criteria of
reasonableness, I should have given up quinine a long time ago. Still, it's
important to make clear that I have not been spending all my time since 1942
trying to synthesize quinine, but I did come back to it every so often. Last
year has been totally quinine-free in thought. And it had been quinine-free
maybe ten years at a time. But I would think about it again every so often,
01:05:00quite a bit. Now I've finally decided to call it quits.
It's not that the problem has been solved yet, not in the terms that I would
consider a solution, or on the terms that modern chemistry has a right to
demand, namely, control of all of the asymmetric centers of that molecule. That
has not been achieved. We've come the closest to that goal of anyone, but we
haven't published our work because our goal of completely controlling it has not
yet been achieved. This has been a sort of leitmotif.
FINE: Between 1942 and 1950, did you ever try to build a ball and stick model of
the molecule because of this question of three-dimensionality. There were ball
and stick models then.
STORK: My favorite story of that--and I don't know if it is mentioned in
01:06:00Hoffman's article--is the time that we completely failed essentially because of
a lack of intelligence; yes, a lack of sufficiently focused acumen. I want to
soften the blow. [laughter] It involved Carl Djerassi when he was a graduate
student. Carl Djerassi and I were overlapping graduate students. I guess he was
a year behind me when he started; maybe, maybe not. We would have lunch together
every day at the lab. Eventually I convinced him he was wasting his time doing a
Ph.D. with Al [Alfred L.] Wilds, and that he should obviously work on my
problem. He agreed that was certainly reasonable. So he started doing that. At
that time the problem I was interested in was morphine. Well, quinine was my own
01:07:00problem, but Djerassi's problem was going to be to synthesize morphine. This
lasted two weeks, until Wilds found out about it and then we were both
threatened with instantaneous expulsion. [laughter] So that stopped us.
But during that period, when he was my collaborator, de facto though not de
jure, we became fascinated by a paper that was published by Indian
workers. We became fascinated, as indeed many people
became fascinated, with an early total synthesis of a terpene called santonin.
Santonin had medical use because it's a vermifuge; that is, you can use it for
cattle to get rid of worms. Its structure was something that was a conceivable
target at that time; it looked tough, but nevertheless it was a conceivable
01:08:00target. It had a couple of asymmetric centers and it had two rings, so it was
something that you could think about. Various people had considered this
substance as a possible target of synthesis, and then, all of a sudden, there
was a series of papers from this group in India, which claimed to have
What became fascinating to us (and I'm sure to a lot of other people) was that
the final molecule they obtained was identical in all respects with santonin,
including its optical rotation. That was startling because no optically active
starting material and no resolution had been used. Therefore, optical activity
had to have been produced in one of the steps. It's actually not impossible,
come to think of it, but the initial reaction today would be that it's a little
bit like saying there's a machine that will do perpetual motion; it violates
01:09:00something--not everything, but it violates something. So we were intrigued by
this, and it was boiled down to a particular step in the sequence. That is, at
what point did the optical activity appear?" Well, it obviously appeared with
the first asymmetric center. The first asymmetric center was sticking a methyl
group into 2-formylcyclohexanone. Most people refer to it as 2
hydroxymethylene-cyclohexanone. So the anion of what you can think of as
formylcyclohexanone was methylated. The methyl group is stuck on and that carbon
becomes an asymmetric carbon. There are four different groups on it, and that
molecule became optically active in the Indian work. So it was the methylation
that produced the optical activity.
01:10:00We decided to find out how that happened. We made these ball and stick models
that you're talking about, the Fisher models. They still exist. There's nothing
wrong whatsoever with the Fisher models. We built this thing to try to
understand how the methylation had to have come from one direction rather than
from the other. They hadn't suggested that this is what had happened. This is
what we concluded and, of course, it didn't make any sense. So we made models to
see whether it was possible. This was probably in 1943.
This was maybe six or seven years before [Derek H. R.] Barton became concerned
about interconverting chairs. If you take Fisher's sticks and balls and you
01:11:00construct a model, you can't make it flat. You can't make it flat; it will come
out as either a boat or a chair. Ours came out as a chair, purely accidentally.
It could have been a boat, but it came out as a chair. If you take a chair,
obviously there's a preferred direction of approach of the methyl group, because
the two faces of the chair form we had made do not have the same appearance.
What's wrong is that another chair would have been made, for which the exact
opposite conclusion about ease of approach would have been reached.
These two chairs did not interconvert easily. The Fisher models did not allow
that. Almost certainly, you could if you were extraordinarily gentle and really
meant to interconvert them, you could have. But they would not interconvert the
way these plastic things that you can get today would just begin interconverting
01:12:00almost by themselves. It would have to be a willful act, and we had no
motivation for this willful act. We just built this thing and it had that shape.
I got Djerassi to repeat the methylation experiment described in the literature
and run off to a polarimeter. (He didn't have his
stiff leg then.) Where was there a polarimeter? Well, there was a polarimeter in
the agriculture school, which was about half a mile down the road. "We"
methylated this formylcyclohexanone, and Carl went to take the rotation of the
product. He ran over to the agricultural place, learned how to use a
polarimeter, found out the rotation, and came back all excited. In fact, it was
01:13:00optically active. Fantastic! We were prepared to write up the bombshell paper.
But then, I guess we were still puzzled and we repeated the experiment. We
decided we'd better repeat it very carefully because it was a pretty dramatic
result; nobody would believe our result. We looked at it again very carefully,
this time washing the polarimeter tube very carefully because it had been used
for the analysis of glucose solutions. [laughter] This time, the second time,
there was in fact, within experimental limits, no rotation.
Now, the obvious, intelligent next step we did not take. Why wasn't there any
activity? Because there was this other equally possible chair, right? That would
have been an important first step. This was known at the time, the theoretical
basis for the two chairs and the boat. These things existed as documents, which
01:14:00we were not aware of. It was not our ballpark, so we didn't know anything about
this. We missed it completely.
Barton and I later overlapped in the sense that he spent a year at Harvard when
I was there. He developed his conformational insights at that time. I was
violently opposed to it. There's no question but that I thought it was
ridiculous, this conformational business, and "polar," now changed to axial, and
equatorial bonds. My objection was both reasonable and stupid; his was
fundamentally not rigorous but brilliant. There's a difference. The difference
is simply that there are things that are not absolutely correct with a capital
"C," but extremely worthwhile because they're major simplifying assumptions,
01:15:00which allow things to move forward. Other people focus on what the little
problems are with this, "This does not explain absolutely everything, and there
are exceptions to this and that." Therefore, they are bogged down with recondite
concerns, rather than perceive the stylization of reality, which allows moving forward.
My objection had been with the polar-equatorial relative stability concept; you
can obviously construct a molecule in which axial would be more stable than
equatorial. That's obviously true, but not as important as the simplification
that the great majority of cases, will be true as a first approximation so that
you can start thinking about things faster than you would otherwise. Today, I
think my objection makes more sense, but it remains that people would have
wasted much time if Barton had gone along with me. Because of the computer,
there is no special reason not to draw and minimize the energy of a structure
01:16:00and see what is more or less hindered. Never mind about calling it axial or
equatorial. So axial, equatorial no longer makes as much sense. But it did at
the time and the resulting progress advance in understanding was extremely
positive. It is definitely to Barton's credit that he paid absolutely no
attention to my objections. [laughter]
So at the time, there were ball and stick models; they could have served
perfectly well. Barton's initial contribution was to have a machine shop make
his initial model of cyclohexane that it was about that big [two feet across].
You could walk into it. You could see cholesterol from the inside. [laughter] If
you put fabric on top of it, you could almost use it as a tent. But the crux was
that it was easily convertible from one chair to the other. Eventually, the
Barton models were used by [Louis F.] Fieser to make the Fieser models, which
were the basis for various other models that are now available.
01:17:00So how did I get into that? Also, what understanding did we have of
three-dimensional relationships at that time? The genius at that time in organic
chemistry was Sir Robert Robinson. I go to England every so often; they still
tolerate me. But one of the things they do not like is what I say about
Robinson. Robinson was a genius. I knew Robinson in a casual way, not
intimately. The only person who really knew Robinson intimately was [John W.]
Cornforth. Cornforth's still alive, and it would actually be very worthwhile to
do one of these interviews with him. It would be tough with Cornforth because
he's deaf. But he can talk and you can learn to interpret what he says. His wife
01:18:00lip-reads, and they work together very well. To do one interview about Robinson
would be very, very worthwhile. Cornforth is the only person who could do it.
[Arthur John] Birch would also contribute things to it, which would be worthwhile.
Robinson was viewed as an intellectual giant and had great influence. Robinson
became identified with synthesis. And this is going to be about as harsh as I
can make it, but his efforts in synthesis were doomed, even making allowances
for that far away time in synthesis. It was a complex psychological thing. He
01:19:00knew he was brilliant, but he considered three-dimensionality an enormous
handicap to the exercise of his brilliance, which was just straining to burst.
Some people have interpreted the supposed feud between [Antonio] Salieri and
Mozart in the terms of a conflict between Salieri and God. This is a romantic
view, but an interesting one. It's an interesting thought, which I happen to
believe is what the problem was with Robinson. That is, Robinson essentially
decided that if God had decided to make things three-dimensional, that was his
problem, not Robinson's. [laughter] And Robinson was able to do actually
fantastic, brilliant things--ignoring the dimensionality. He did this, but his
synthesis efforts were doomed.
Now, if you think about it, it is unbelievable. How can you possibly try to
synthesize steroids if you behave as though you thought that they were pancakes?
01:20:00There's just no way you can do it. And he never did! Robinson published
sixty-nine, or some such number of papers on attempted steroid syntheses, an
incredible thing. You couldn't get away with it today in a million years.
Sixty-nine papers on the total synthesis of steroids, without ever synthesizing
a steroid or anything looking like a steroid. What he did looked like steroids,
because they were two-dimensional pictures, actually unrelated to the steroids
he was trying to duplicate, and which, he was allowed to publish because he was Robinson.
He did eventually achieve an impressive steroid synthesis, but only when
Cornforth decided it was enough already. Toward the end of Robinson's life, he
took the various chemicals out of the lab to his place, which I think was at
Shell Laboratories at that time. (Shell had given Cornforth a lab.) He managed
to beat together a construction, which you could claim was a cholesterol
01:21:00synthesis. Not entirely obvious, really because identification methods were
In that era there was an important effort relating to the structure of
strychnine. Eventually, the correct structure of strychnine was solved by
[Robert B.] Woodward, and this produced much tension between Woodward and
Robinson because Robinson had devoted much of his life to the structure of
strychnine problems. And there was this interloper, who moved just one bond from
here to there while leaving all the others where Robinson had put them
(correctly). But of course, you see, Robinson's argument was, "Well, what the
hell. There's only a one percent change, and Woodward gets all the credit." The
counter argument is, "If you tried to use a key with one percent change from the
key that would open a particular lock, it would very likely not work." Robinson
then said, "Oh well, it's not easy to decide what the correct structure is. The
obvious thing to do is to synthesize all the variants that are possible for
strychnine." This would, even today, be inconceivable, especially because he had
no clue what the stereochemistry was. He started with a coworker by the name of
[H. T.] Openshaw and published a couple of papers trying to put together
strychnine. There were interesting kinds of structural
01:22:00changes, but no conceivable possibility of any kind of strychnine. So that was
the state of affairs. Robinson gave no evidence of conscious interest in
three-dimensionality; it's really remarkable. The molecules that he really did
synthesize were various flat things like flower pigments and things like that,
which were nice, flat synthetic problems.
Robinson did brilliant structural work, intuitively and otherwise. He did one
synthesis for which I'm willing to forgive a lot, which is his famous tropinone
synthesis. It was 1920 or something; it was really pretty
early. He did that, which involved mixing three
chemicals, and that's fantastic. But that's it. I'd say, "Well, what did he do
01:23:00after inventing fire?" [laughter] But it's really pretty good. It's really not
bad. But that was when he was very young. And there was really no
three-dimensionality involved in it. He just looked at the two-dimensional
structure and said, "Well, it should be possible to mix succinic aldehyde and
acetone and hydrochloric acid with something like methylamine," and it turned
out to be true. But again, there was no conscious interest in three-dimensionality.
Woodward had no great interest in consciousness three-dimensionality at first,
although when he started he was being vaguely conscious of
it. One of the things that has riled me over the
years, as it obviously would because it has to do with quinine, was the
absolutely preposterous handling of the Woodward quinine synthesis by both the
scientific establishment and the press such as The New York
Times. What would one expect? He was only twenty-six.
That's pretty good. A couple of kids supposedly made quinine and that obviously
01:24:00produced a big impact. The fact that Woodward never made quinine, and I'm saying
this on the record, the fact that he and [William von Eggers] Doering never made
quinine, was unknown to the lay population. The second fact is that if they ever
had made quinine, it would have cost the national debt to make ten milligrams of
it, by that operation. The third fact is that the synthesis was meant to follow
the Rabe hydroquinine synthesis; except that ethyl groups of the Rabe
construction was now to be a vinyl group. The Woodward contribution was an
elegant construction of certain piperidine with two asymmetric centers, but the
attempt at stereo control failed and they got two different compounds, one
right, one wrong. It is the maximum that you can get with two asymmetric centers
in a vacemic compound.
From there, the synthesis followed the Rabe construction step by step until they
got to a point where they said, "Well, it's well known that this can be made
01:25:00into quinine because Rabe said so." Rabe went on publishing very fine chemistry
for another ten years, but he never published details that would allow anyone to
repeat his supposed conversion of the two asymmetric center intermediate
"quinotoxine" to target the quinine. Some people tried to repeat the word
description that Rabe gave of how one could do that conversion from quinotoxine
to quinine. They could not do it. So you can't make quinine that way. So quinine
01:26:00was not synthesized in 1944, even though it was the central story on the first
page of The New York Times at that time.
So the quinine sequence had nothing to do with the control of
three-dimensionality of stereochemistry. Every time an asymmetric center was
encountered, two compounds were obtained. At the next bifurcation, two more
compounds were obtained. It was marvelous experimental work, because before IR,
before NMR, if you got two stereo isometric compounds you couldn't get anywhere
unless you could crystallize them. Then, you would take your chances going on
with one at a time to see which one would go on to the correct next compound.
(You can't do this if you've got too many asymmetric centers.) In this case, one
had to take quinine and break it apart to a point where you can identify whether
the synthetic intermediate matches the degradation product or not. This, in
fact, is what they did. They synthesized the piperidine, which they
deconstructed quinine to, and at that point took the degradation product from
quinine, built it up to compound Q, the one Rabe claimed could be taken further
01:27:00to quinine; which in fact, you cannot.
[END OF TAPE, SIDE 3]
STORK: So that was the state of organic synthesis in the world at that time when
I tried to make some contribution to it. The quinine synthesis was in 1944. By
that time I was fiddling around trying to make quinine, and as far as I know
this was the first conscious effort to achieve stereo control in a synthesis. My
effort was designed to make specifically the required cis-3, 4-disubstituted
piperidine, rather than a mixture of the cis and the trans. The nitrogen is
01:28:00position one; in the three-position is the vinyl group and in the four-position
there is an acetic acid residue. That substance was called meroquinene. My
synthesis was designed, and eventually demonstrated, to give only this cis
system. But in fact, I did not succeed in getting a vinyl group where an ethyl
group is in the simple dihydroquanine, which was the Rabe intermediate.
Achieving the correct stereochemistry was part of my Ph.D. thesis in 1945.
I was extremely impressed by The New York Times reports because I had no reason
to doubt the validity of the quinine synthesis. I remember I called Woodward up,
because the reported synthesis was only in the newspapers, not yet in the
professional journals. I wanted to know how he made it, so I called him up. I
01:29:00still remember it. (These are the things that stick in your mind.) At that
historical moment, what were Woodward's first words on the telephone? His first
words were, "Do you have a pencil?" [laughter] I still remember that. So then we
started talking about the synthesis and in fact I'm still pretty impressed that
I got all this information correctly on the phone. I was especially interested
because I was supposed to give a departmental seminar a couple of weeks later.
This was really a hot, fresh topic, so I was able to do that.
The operational awareness of three-dimensionality in synthesis started around
that time. Various things converged. Usually things get to a stage where the
stage is set for something to happen and so it happens. (Quantum mechanics may
01:30:00have been an exception; I'm not sure. I guess relativity probably was.) So there
were various people who became conscious of that problem at the time. One of
them was unquestionably Bill [William S.] Johnson, who had become a young
assistant professor, just before I got to Wisconsin. Although I did not work for
Johnson, we interacted (and still do) to a considerable extent. He was conscious
of stereochemistry. In fact, his early effort at Wisconsin was to find a way of
solving the problem of making the trans-C/D system of steroids. They are trans
fused rings, the so-called hydrindane system, with a so-called angular methyl
group, which is placed so as to make a trans rather than a cis system. The
question is, how do you achieve that? First of all you have to solve the
regiochemistry problem. How do you stick the methyl in the angle? Johnson was
very much concerned with that. And after you've found a way of sticking the
methyl in the angle, how could you conceivably control getting it so as to give
01:31:00a trans rather than a cis ring junction? Consciousness of three-dimensional
problems started around that time. Which is also more or less the time when we
had our big fiasco with the Fisher models.
That sort of problem has been central in my own research. The major thing that I
have been concerned with in my scientific career has been control. One is
position control. I was extremely antagonistic to the term "regiospecificity"
when Barry Trost proposed it. I was not against "stereo" specificity, but for
regiospecificity, I thought, "What's wrong with site specificity? Why regio?"
That's because you can make it one word while the other is two words. I think
01:32:00both terms have by now established themselves as very useful concepts. My own
interest has been the control of regiospecificity and of stereospecificity. That
concern is central to practically everything that we've done.
I actually had no idea where to go after I got my degree at Wisconsin. My
background was that a job was what you needed to do in order to be able to buy
some food and pay the rent. But, otherwise, you did what you wanted to do. At
Florida, I did that on the side because I was allowed to. At Wisconsin, McElvain
was a great man. He was both a very tough leader and very tolerant, both
01:33:00tolerant and intolerant. He let me do various things, up to a point, to the
point where I passed the limit. I guess he became very upset when he found out
that although I had claimed I was trying to synthesize quinine, on the floor
above him, I was, in fact, trying to make biotin. And you could tell; you
couldn't hide biotin with the sulfur in it. [laughter] He found that suspicious
in the once-a-year visit that he made to the floor above his floor, where I was.
It smelled of sulfur, not of ammonia, not of base. So then he found out what I
was up to.
I also did not know you were supposed to put your professor's name on your
papers. It shows how tolerant McElvain was. Most people would have been very
upset. He flipped slightly, but not too much, when he picked up a JACS and saw
there was this communication, my first paper. That
01:34:00first paper also has the distinction of having only one melting point mentioned
there; it's wrong. It actually had to do with furan chemistry, because I
intended to transform the furan ring to the thiophene ring of biotin at the end.
It could still be worthwhile. Maybe I should make biotin that way before I
retire. [laughter] The idea was to build a furan system because it's much easier
to handle oxygen. That is, it is much easier to do chemistry with furan than
with thiophene, in particular, when you have to reduce the rings. Sulfur is a
catalyst poison, so it's very hard to hydrogenate the ring. My idea was really a
good idea. It turns out that biotin has all three substituents on the same side
of the ring plane, all cis to each other. If only you could build the thiophene
analog of biotin and then hydrogenate it, automatically the substituents would
all end up cis and that would be the solution to that problem. But you it's hard
to do, because sulfur is a catalyst poison. So the idea was, let's build a furan
01:35:00system, reduce it so the stereochemistry will be right, and then change the
oxygen into sulfur. That could be done with two inversions and so, you would end
up with the dull cis stereochemistry again. That was actually pretty good. It
was never tested because McElvain said, "You cut this fooling around out," and
he moved me next to his office. [laughter] Then I started working more seriously
on trying to make the piperidine derivative, which one would presumably require
But I had in fact no great thought at that time about how to do it better than
Rabe had done, from that point on. It would be better than what Woodward
eventually did, namely, to make both the cis and the trans and separate them.
Nevertheless, that would leave these subsequent problems. Milan Uskokovic,
several years later, at Hoffmann-La Roche, was the first one to make a major
01:36:00dent into these subsequent problems on the route to quinine.
BOHNING: In that first paper, at the very end of it, you said, "Work in this
Communication had to be discontinued almost two years ago." What did that refer to?
STORK: Well, that was McElvain saying, "You cut that out."
BOHNING: So that was it. I was struck by that comment. That's the last statement
in the paper.
STORK: That paper also is unusual in the sense that only my name was on it as
author. My feeling was that I was independent so far as I knew. Nobody was
paying me. I was working on my stuff. I had a job analyzing fertilizer in the
state experimental station. So I was not conscious that there was a problem there.
BOHNING: That's how you first supported yourself, wasn't it, doing those
STORK: That was kind of fun. You'd spend a certain number of hours and it was
01:37:00flexible. But I was interrupted by McElvain, for very good reasons.
But as I said, that melting point was a misprint; I think the two last digits
are inverted. I forget what it says; does it say 113 degrees or 131 degrees or
whatever for the melting point? It's the melting point of the diazide. [reading]
"Melting point 166-167 degrees." Yes, I think it's 176 degrees. I forget exactly
what it is, but it's one of those digits that's wrong. I was shocked. I was
shaken, because my melting point's wrong, and now it's published in the
literature. So I wrote to Chemical Abstracts and said that when they abstract
this thing, they must put down the corrected melting point in the abstract. My
abstract is the only abstract, so far as I know which has a note that says,
"Private communication from the author." [laughter]
It does say that, actually; it's a private communication. Chem. Abstracts no
01:38:00longer does it. There are no more private communications to Chem. Abstracts.
BOHNING: Carl Djerassi has said that he learned more chemistry from you than
from anyone else at Wisconsin.
STORK: That's probably true. That's probably true, because as I said, we had
lunch together every day. Besides, even if it was for only two weeks, he was
sort of my graduate student. [laughter]
BOHNING: He also said, "[Stork] worked on four different projects without his
supervisor knowing it, and he conned me into working with him on the morphine
approach on the side." [laughter]
STORK: Oh, he said that? Well, that's pretty good. Yes, that's true. At that
time he was in the hospital; when I "conned" him he was weakened. [laughter]
That's true. He was in the hospital. I don't remember what was wrong with him,
but it was nothing terribly serious. He was in the hospital, so I went to visit
him and used the opportunity to convince him he should work for me.
There is a connection between that and this sudden interest in this Indian work
01:39:00that claimed to have synthesized santonin. The reaction we wanted to use as part
of one construction of the ring of morphine was in fact one that these people
claimed to have used. One major clue was this stereochemical thing. It was a
paper construction, but it was an intelligent paper construction. That is, it
was an interesting scheme. It involved a reaction which was unknown at the time,
but which was conceivable, and which I thought was a great way to put morphine
together. As it happened, we never tested it with morphine because that project
was also interrupted by the furan stuff. But it turned out that Djerassi's Ph.D.
thesis with Wilds was to study this reaction as a possible way of making steroid
rings. And it can, in fact, be done; Djerassi was the
first one to bring it to practice this reaction, which supposedly had been done
01:40:00by this Indian worker who never went to a lab. Actually, Wilds and Djerassi
found a way of making it work, but we never, in fact, applied it to make morphine.
So at that time, people like Johnson were becoming conscious of the
three-dimensional problem as more than a passing thought; they were actually
trying to do something about it. I was trying to do something about it.
Cornforth was later, in his published stuff, but if Birch said to me that
Cornforth was thinking about this really seriously then, I wouldn't be surprised.
FINE: What about [Robert C.] Elderfield?
01:41:00STORK: No idea. No clue. Elderfield was a pioneer in chemistry, but his field
was not synthesis; it was structure. His big contributions were damaged because
he did not get the correct structure of the sapogenins. The sapogenins are
steroids, which have a cholesterol side chain at the top, which is connected by
oxygen atoms to some other part of the molecule. It turns out that we know today
that the two oxygens are connected to the same carbon atom; it's a so-called
spiroketal. Elderfield thought it was a diether, with the two oxygens on
adjacent carbon atoms.
But he was a pioneer, and Elderfield did have one major contribution. Well, he
01:42:00made major contributions to the structure of the sapogenins. But Elderfield
worked with [Walter A.] Jacobs, who was a professor at Rockefeller Institute.
They did the major early work on the structure of digitoxin and digitoxigenin.
(The drugs that they used on [George] Bush recently.) These compounds are what
we call cardiac glycosides, because there's a steroid attached to some sugar.
Elderfield did make major contributions, even though he was wrong on the
01:43:00structure of their side chain, to the structure of sapogenins such as diosgenin.
This diosgenin became the Mexican source of steroids for cortisone and
progesterone construction. The interesting story of that is that the person who
correctly got the structure for the sapogenin was Russell
Marker. So far as I know he's still alive, although
obviously ancient. Marker's reputation was so bad at the time that [Louis F.]
Fieser completely endorsed the Elderfield structure, which was incorrect, simply
because Marker was obviously a rogue, and therefore what a rogue does is clearly
bad. There's a logical gap there, but it's a common mistake. That is, this guy
is a bum, so what he says is probably not right, but in this case it was very
01:44:00But Elderfield did make extraordinarily important contributions. First of all,
he was one of the early people to do serious structural work in this country.
That's not something that has perpetuated itself, unfortunately, in the U.S.
It's unfortunate that people don't do much structural work. I mean, the major
people were brought up abroad. The two major lights in this country are [Koji]
Nakanishi, who's here, and who obviously was brought up in Japan. You couldn't
possibly start this work here; you would never get tenure. And Ian [Alastair]
Scott, at Texas A&M, who is from England. You can't start this type of work here
simply because of the enormous amount of effort and work required. You really
have two years to make an impact here. The system is based on marketing. I mean,
it is based on marketing in part, and obviously on accomplishment as well. But
01:45:00it's not enough to devise a better soft drink; you've got to beat Coca-Cola. So
there are two aspects to it. But Elderfield was one of the people that was doing
serious structural work. He has unfortunately died.
Roger Adams also did some serious structural work. One of my first pleasures in
organic chemistry was at Wisconsin when I gave a seminar on Roger Adams's
structural work on some bicyclic alkaloids, at the moment I forget their names,
(I think one of them was retrnecine). I concluded that the suggested structure
was clearly incorrect. I felt it was a great accomplishment because at that time
a graduate student did not do that kind of thing. It is not to say there was any
kind of showmanship. It was just the inescapable conclusion; this thing was just
01:46:00obviously wrong, that's all. I still remember the palpable shock of the front
row with Homer Adkins and Bill Johnson because first of all, it was unusual for
a graduate student to question his elders. Second, Roger Adams was Roger Adams.
Incidentally, it turned out eventually that, he was, in fact, quite wrong. So
that was nice.
Elderfield's other great contribution is that simultaneously there were three
major people in his research group here, who are probably the three best known
alumni of that from Columbia. All three were graduate students at the same time.
One was Nelson [J.] Leonard. Another was Josef Fried, Gus Fried, who eventually
developed the fluorosteroids when he was at Squibb; he was director of research
at Squibb. He was here the same time as Nelson Leonard; they're still very good
01:47:00friends. And the third one is Elkan Blout, who became director of research at
Polaroid. His history is quite remarkable. He eventually became head of the
biochemistry department at the Harvard Medical School. That's quite a thing,
going from the director of research of a photographic company.
BOHNING: What about Louis Fieser? How did he fit into this picture?
STORK: Louis Fieser was both a major strength and a major catastrophe in
American chemistry. (I assume these things can be edited.) [laughter] Fieser was
a nasty man in contrast to Woodward. In contrast to Woodward, Fieser was
01:48:00absolutely unable to separate his emotional feeling about somebody from his
intellectual, rational feeling. This is the reason he got into trouble with the
sapogenin structure. If he did not like somebody, the guy was just a total loss,
regardless of what he did. Woodward was able to dissociate the two. He was quite
capable of viciousness, but it was a highly intellectual, structured
viciousness. It was not emotional. When he was rude, he knew he was rude and was
rude for a purpose. Fieser was just different.
01:49:00At one time when I was at Harvard we wanted to invite [David Y.] Curtin for a
colloquium there. Fieser would absolutely not allow it. He would not tolerate
it; we could not invite Curtin to give a talk. What he had against Curtin is
that he spent a fair amount of his time on an individual, independent
postdoctoral fellowship, a National Research Council Fellowship which allowed
one to do some work on his own. Today, of course, we make slaves of them as soon
as we can. [laughter] Curtin annoyed Fieser because he felt he was spending too
much time with [John D.] Jack Roberts, trying to learn some physical organic
chemistry, rather than making some more naphthoquinones that might be good
01:50:00antimalarials. Fieser was that way.
Once it turned out that we had made a compound that he wanted. It was simple,
but had never been made before. It was 6-hydroxycholesterol. He wanted to know
whether he could have some, and I gave it to him. It turned out it was not as
pure as it should be; it was crystallized, but it was not as pure as if we had
crystallized it more carefully to get the melting point higher. Fieser was an
outstanding experimentalist, no question about that. It was just a bitter
experience for me. Fieser complained about my compound in a department meeting.
I gave him this stuff as a gift, you know. I didn't say it was pure, and we
hadn't published anything. It was just a research chemical that we were fiddling
01:51:00with. But he was capable of being extremely nasty, extremely nasty.
But, he had some good features. He was a great lecturer, clearly. Many people
became fascinated with chemistry because Fieser wrote [Vladimir W.]
Markownikoff's name on the board in Russian letters. He had a certain
showmanship, which was in fact very suited to his teaching. He also wrote well.
Mary Fieser forced him to write well, and he did that. He was nice to her. She
still is alive and, personally, I find her extremely interesting. But he was
very different. He liked cats, which is a positive sign, I guess; I don't like
cats. But that's nothing against cats, because I don't like things that move,
whatever they may be, cats, dogs, whatever. So he was obviously capable of
empathy, if he wanted to. [laughter]
01:52:00But fundamentally, he was a person you didn't want to cross. As an extreme case,
I'm sure you've heard the story of Don [Donald J.] Cram's thesis. You must have
done an oral history on Don Cram. Don Cram may be too much of a gentleman to go
into this, but I still remember at Harvard, when I was an instructor, and Don
Cram was a graduate student. Don Cram came in late because he had been at Merck
for a few years after he got his bachelor's degree, or master's degree, or
something, and then returned to doing a graduate degree five or six years later
than other people. So he was older than they were, but he was a graduate
student. Fieser absolutely could not tolerate the fact that Cram talked to
Woodward more than Fieser thought would be reasonable, because after all, Cram
was working for Fieser, and there was tension between Fieser and Woodward.
Actually, Woodward did his best to exacerbate the situation by missing no
01:53:00opportunity to tell everybody how stupid Fieser was, including the graduate
students working for Fieser. [laughter] So that contributed to the tension in a
not inconsiderable extent.
Cram made a bunch of naphthoquinones. In fact, he made like forty
naphthoquinones or so. In those days, you did C and H analyses. This is an art
that Professor Fine is trying to reinstitute at Columbia, by getting an
instrument that can do this. [laughter] The normal way of getting the analyses
done then was to send them out, normally to MIT; it was a perfectly good
analytical laboratory, under the direction of somebody by the name of [Stephen
M.] Nagy, however you pronounce it. He ran the place, and you sent the compounds
there. Your sponsor had to pay, that was the tradition. You had to pay maybe
five dollars per analysis. It was quite a bit, actually. It was some number like
three or five dollars, which would be like twenty-five dollars today, for the C
01:54:00and H. By the time the Cs and Hs had to be done on the compounds for Cram's
thesis. Fieser just simply refused to pay for the analyses, even though the
compounds were quite pure because Cram was a good experimentalist. He said,
"I'll sponsor your thesis, that's fine with me, but..." I mean, he didn't want
The normal reaction to that would be one of despondency. Cram's response was to
go to the stockroom, check out a pipe, a Bunsen burner and I don't know what,
some drying tubes, what have you. Within a day, he had assembled a macro set-up.
He had grams of these compounds, so he took three hundred milligrams each of
01:55:00these compounds, burned it in a sea of oxygen, weighed the soda lime tube, etc.
He did the whole damn forty analyses over the weekend. And you say, "Well, what
has that got to do with anything?" Well, that was really pretty impressive. So
Cram did that and he presented his thesis. I'm not sure, in those days, that
there was any public defense at all. You turned in your thesis and the committee
accepted it or not. There may not even have been a final exam or anything. I
think you just turned it in and it was approved or not. So Cram turned in his
01:56:00thesis, and eventually sent a copy of it to Fieser.
[END OF TAPE, SIDE 4]
STORK: On the acknowledgement page it said, "To Professor Fieser." Fieser called
it outrageous, ripped it up and mailed it back to him. That was Fieser. And it
lasted years. Cram was invited to give talks at Harvard in subsequent years,
because of pressure by the rest of the department. Fieser would never go to
them. Eventually the ice started breaking slowly when Mary Fieser, who had
originally not attended them either, out of loyalty, began to go to Cram's
talks. By that time Cram was at UCLA. But once in a while he would be East, and
so he would give some kind of talk. I think eventually Fieser may have gone to
one of them, towards the end.
01:57:00But Fieser was that kind of a person--petty. On the other hand, he was a
brilliant experimentalist. At Columbia there was an instructor who got himself
drafted at one point, or whatever the occasion was (I now forget). A temporary
replacement person was found. His name was Ed [Edward N.] Trachtenberg who
eventually became a professor at Clark University in Worcester. Trachtenberg was
in charge of the organic laboratory, among other things, and they were using
Fieser's manual. Fieser loved cheap gadgets that you could make into useful
01:58:00things, like a cleaned-up tuna fish can as a possible water bath, or steel wool
to make packing for distillation columns, which is actually not such a bad idea.
This was before stainless-steel steel wool, so it had its limitations. The
manual recommended that you distill the compound through a distillation column
"with a side arm, tightly packed with steel wool." That is the sentence that was
there, in spite of Mary Fieser; that's what it said, without the comma. So, one
of the sights, which was pretty impressive, was this poor guy packing the side
arm tightly with steel wool, which is what it said to do. [laughter] He was
trying to push the thing through, without great success.
A more serious problem in the book was with a synthesis of isatin. The whole
class was doing this. There were three steps; a goes to b goes to c, and
01:59:00eventually you get some nice crystalline stuff. Out of a class of forty-five
people, only two people got these beautiful crystals. Eventually, under careful
questioning by Trachtenberg, they admitted buying the stuff downtown. [laughter]
For the rest of them, it didn't work. I mean, it just did not work. So we called
up Fieser and said, "This thing doesn't work. You don't get any crystals." He
said, "Give me a few hours to check this." By God, three hours later he called
back. He had run through the whole thing. A good experimentalist is not
necessarily a good person to describe what he has actually done because he does
these things kind of intuitively, right? You write down the recipe for the apple
pie later. At one point Fieser had added a little nitrobenzene. The recipe said,
"1 cc." The way he really did it was to add the nitrobenzene until the solution
02:00:00became opalescent, slightly turbid. At that point he felt it looked like a cc.
So he wrote down "add one milliliter of nitrobenzene." It turned out that if you
add any more than .5 cc at that point, you don't get any crystals. But he had
found this out within three hours, had redone the whole thing and this time
actually measured what he put in there. As I said, he was a very good experimentalist.
But he had no feeling for stereochemistry, either. In Switzerland, [Albert]
Eschenmoser was probably the first one to have that as a serious concern. Some
02:01:00of the older people, like [Leopold] Ruzicka, became interested, but it was still
just something that was looming on the horizon. He was interested, but his work
was not really related to that. Eschenmoser, and of course eventually [Duilio]
Arigoni, became very much concerned.
BOHNING: What about [Tadeus] Reichstein?
STORK: Reichstein was not really terribly concerned. Reichstein was concerned
with intercorrelation of things and did, of course, find the structure of all
these important compounds in the adrenals. It was magnificent, magnificent
experimental work, which was, as you probably know, done with a great
experimentalist, [J.] von Euw. Von Euw was a person who never had a degree, but
was able to crystallize anything and worked with Reichstein his entire career.
02:02:00Reichstein himself was very good, extremely good, as an experimentalist, but he
was not particularly concerned with three-dimensionality. Eschenmoser was.
Eschenmoser was and, in fact, contributed to the solution of stereochemical
problems, even at a fairly early stage. Eschenmoser and I are still on friendly
terms; we have antagonized each other, but we are on fundamentally fairly
friendly terms. I was the first person to ever invite him to the United States,
when I recognized, when he was quite young that he was really very good. I
invited him to a Gordon Conference, which I was chairing at the time. That was
the first time that anybody outside Switzerland paid any attention to Eschenmoser.
BOHNING: So you and Johnson were really kindred spirits at Wisconsin, then.
STORK: My interest in chemistry was much more closely related to that of
Johnson. We knew that and we would talk once in a while; not as much as Johnson
02:03:00talked to Wilds, but we were kindred spirits, yes. Eventually after I had left
with my Ph.D., Johnson is the person that I would come and visit in Madison.
My first post Ph.D. job was in Milwaukee for a year. I could not be employed by
anyone because I was illegally in the United States. Not really illegally, but
it was not legal for me to work because I had only a visitor's visa. When I came
to the U.S. with my parents, I came as a visitor, as a tourist, and obviously I
couldn't work. Now today, you couldn't get away with this. Well yes, you could
be totally illegal today; you could get away with it, but you wouldn't be
employed by any kind of serious corporation. That was sort of true then but, not
as completely true. This particular place in Milwaukee, Lakeside Laboratories,
was run by the so-called director of research, which was a euphemism in this
02:04:00case. He was a former Ph.D. student of McElvain. McElvain conned him into giving
me a job even though I could not really, legally have a job. I actually checked
with the Immigration people whether I could get away with it, and they were
very, very nice. They said, "We cannot give you an answer that it's okay," which
I interpreted to mean that it was okay. [laughter] It certainly didn't bother
me. Eventually I got it resolved. It was not easy to straighten this thing out,
because of course there were war conditions, and so various papers and documents
that I needed were difficult to obtain. During the time that I was there, I
would come back to Wisconsin once in a while, and I would see Johnson and talk
about whatever I was doing.
At that time my main interest, other than the medical chemistry for Lakeside,
was to try to synthesize estrone, which I would work on after hours, at night.
02:05:00The one piece of equipment they had was a high-pressure hydrogenator. So the
question was, how could you use this to make estrone? It's quite crazy. I was
senior research chemist at Lakeside Laboratories, a title that has to be read in
the context, which I may as well explain to you. That is, I was the only
chemist. I was the only organic chemist there. There was also an analytical
chemist and a lady who set up equipment and washed the glassware. My great
contribution to pharmaceutical science, which came to nothing (none of these
chemicals were ever tested and it probably would have been stupid to), was
essentially to plagiarize every interesting benzene-ring thing, like ephedrine
or whatever, by making the thiophene analog and see what it would do, whether it
behaved differently. I guess it's not totally ridiculous in the context of the time.
I remember one paper that had fascinated me at Wisconsin; it was a paper by an
02:06:00Englishman by the name of either Wood or Woods. I don't remember. It was in
Lancet. Why I got to this paper, I can't imagine. It was the first postulate of
the rational design of drugs. He had discovered why sulfa drugs worked, which
was something I was interested in at the time because of penicillin. He equally
became aware of penicillin; the next question, was, "Now, how do these things
work?" I remember reading that paper in which he demonstrated, or maybe just
postulated at the time, that sulfanilamide was antagonistic to p-aminobenzoic
acid, which was an essential substance. I thought it was fantastic, fascinating.
So penicillin, I thought, must work that way, too. At that time, the penicillin
work was kept secret, so there was an awful lot that everybody who was involved
in it knew, that I didn't know anything about. So I thought I had great
02:07:00thoughts, and of course they were about two or three years behind the times. I
wrote my great ideas up and dashed off a paper to Science; it became my first
rejected paper. [laughter] I dashed this paper to Science about the mechanism of
action of penicillin. I was fascinated by the fact, which I didn't understand,
really--that penicillin is made up of amino acid like structures, which was a
D-amino acid, not an L-amino acid. My idea was that penicillin could be a mimic
of an important tripeptide, which at that time I thought was glutathione, and
that penicillin, which had also a sulfur amino acid in it, was an antagonist to
glutathione by virtue of the fact that one of the amino acids was the mirror
image of what it normally would be. So I sent this great thought, which in fact
02:08:00was wrong, to Science, which promptly pointed out that thoughts of that type had
been coming for quite some time. It was naïve.
A year later I was at Lakeside, and trying to make thiophene analogs to keep the
research director off my back, and he was quite tolerant. I was trying to make
estrone, and then Johnson suggested that I apply for an independent postdoctoral
fellowship that had opened up at Harvard. I don't know who funded it. So I wrote
up the estrone approach that I was working on. It is still great. Actually,
considering the time, I think that it was absolutely great. I don't think I've
actually cooked up anything better than that since then. It really was not easy.
02:09:00It had a least two new reactions in it. They were not known, but I presumed that
they would be possible. They're both known now. They were to give complete
control of the stereochemistry of all four centers of estrone. This schedule was
never really attempted in the laboratory, and today it would be pointless to do,
but it was really quite nice.
I sent my estrone scheme in with my postdoc application, and Woodward saw it,
and Woodward talked [Paul] Bartlett, who was at that time chairman of the
department, into offering me an instructorship instead. I was pretty young. At
Lakeside the entire research laboratory was half this room, and the rest of it
was extracting urine from pregnant mares to get some hormone preparation out of
that. There was one phone in this place, against the wall; the phone rang and it
02:10:00was Paul Bartlett, who said, "We have your application. Would you consider an
instructorship?" I said, "Sure." [laughter] So that afternoon, I wrote a nice
letter of resignation from the Lakeside Laboratories. It was run by a very nice
man by the name of [Evan P.] Helfaer, who became of some importance in chemistry
because he eventually set up the Helfaer Chair at Wisconsin, which [Barry] Trost
eventually occupied. (Trost was the Helfaer professor at Wisconsin before he
went off to Stanford.) I never was particularly concerned whether I would go to
industry or academe. I never thought about it! I could do work; all I needed was
02:11:00a lab and equipment and I would do my stuff. Completely preposterous. It was a
completely romantic, preposterous view of mine.
BOHNING: You published those two papers on the tetralones though, while you were
STORK: Yes that's right. There was a hydrogenation machine there, so you could
do those things. The tetralone was a starting material that I was going to use
on my estrone synthesis, so that was the connection with that.
BOHNING: But those papers actually had some far-reaching effects. You did the
acid-base work to show the potential selectivity of the catalyst.
STORK: I don't know about far-reaching.
BOHNING: Well, nobody had done that at the time.
STORK: No. Nobody had done that. They're not far-reaching, but it was an
important, narrow thing. It's important because all the aromatic steroids are
made starting with 6-methoxy--tetralone, which is made by my process. Which
unfortunately, if you know anything about patenting, you know that I didn't.
[laughter] So the first step is in fact the hydrogenation and yes, it was
02:12:00actually quite interesting. What I suggested as the reason for that, and I'm
still not certain that it's not right, is this: You have two aromatic rings in
-naphthol. One ring reduces before the other. That's not surprising; it's easy
to reduce one ring in naphthalene and after that it becomes a benzene. It stops
after one ring. The thing that's surprising is that if you do it on a basic pH,
the ring with the OH gets reduced. I'm talking about Raney nickel reduction,
high-pressure hydrogenation with nickel. The hydroxyl ring gets reduced. If you
do it in a neutral or slightly acidic pH, it's the other ring that gets reduced,
which is the basis for the tetralone business because you want the phenolic ring
to remain. The suggestion was that the reason for reducing the naphthalene in
the non-substituted ring was that you produced that compound in a non-perturbed
02:13:00condition. You had to view that base perturbed it because now you reduced the
phenolate ion rather than the phenol. But any substituted naphthalene, whether
it was electron-donating or not, whether it was 2-carboxynaphthalene or
2-methylnaphthalene or 2-hydroxynaphthalene, you would always reduce the
unsubstituted ring because that resulted in the smallest loss of resonance
energy. That is, it's final product was in fact stabilized by these
substituents, whatever they may be, because of the interactions of the
substituents. Today if you tried to validate this, you would say, "Well, that's
not that completely crazy because hydrogenation and dehydrogenation are
obviously related and so that it could be an equilibrium ending with the more
stable of the possible tetrahydro compounds. It's not that surprising." But that
was in fact an interesting thought, and in base the idea was that the O-ring was
02:14:00now more strongly absorbed on the catalytic centers because it was an electron donor.
We still don't understand catalytic hydrogenation, so I can get away with that
kind of stuff. It's a very difficult thing to which I have made no contribution,
but it was interesting. That was the origin of the easy access to
methoxytetralone. But it was not any kind of intellectual conception because
although one can hang onto that little bit of a suggestion, it was not developed
and did not really have any impact that I know about. Per se, it was an
important little thing I did there.
The other one that I did was patented and was actually used by
people. The beta-tetralone was different; it was the
high-pressure reduction on palladium, which actually had not been tried at that
02:15:00time. We actually reduced the hydroxyl ring to the dihydro stage, because in the
dihydro stage the thing would become a ketone, -tetralone in this case. The
palladium was known not to be a very good catalyst to reduce ketones. So there
was a chance that you could take this aromatic thing and reduce it to ketones,
which in fact turned out to be right, probably for totally different reasons.
But it turned out to be right, and is actually a Lakeside patent. As my
contribution to show that I was actually doing something, I worked up that
patent. I have never had my name on any patent, which ever made any money at
all, except one, which is the Syntex patent. It
didn't make any money for me, though, and probably didn't make much money for
FINE: Did you have much to do with [Homer] Adkins? You did all this work on hydrogenation.
STORK: I had very little to do with Adkins because Adkins at that time was
02:16:00involved in secret, war-connected work which he was not allowed to discuss. The
theses of his people were sealed; there were very special arrangements with the
university to make it tolerable to get a Ph.D. under such conditions. I knew
Adkins was involved in hydrogenation. I got recipes from the Adkins group on how
one makes Raney nickel, which he had many recipes for. Adkins would come to
seminars and make statements, so he was highly respected, but I never interacted
BOHNING: There's a story about how you didn't last as a T.A. at Wisconsin.
STORK: All of it is true.
BOHNING: It's all true. [laughter] Hoffman talks about that.
STORK: There was a preposterous guy who was running it. I was teaching a section
02:17:00of the Army Special Training Program, ASTP or something like that. I was
supposed to teach them chemistry. I claim I invented the "flash card" system of
learning nonsensical stuff, which was already known for language learning. So I
didn't invent the whole system, but the idea of perverting chemistry by using
this kind of disreputable technique was probably mine, and this is in part why I
got fired. It was the last straw, when my section, which was stupid--they were
stupid--got the highest grade on the next exam that they took. There were
hundreds of people taking the exam, so it was statistically significant. All of
a sudden, my group of benighted people got the highest grade on the exam.
[laughter] The rational hypothesis was that I gave the answers to the questions
02:18:00ahead of time. This was, of course, not true. [laughter] What I had done was to
make a whole stack of cards, which would say "zinc plus sulfuric acid" on one
side and "H2 plus zinc sulfate" on the other and so on, for everything that is
conceivable that you could learn in that particular period. Then I went to the
army barracks or the dormitories, or whatever they were. They all sat in a large
circle and copied this whole stack, each one. Then I told them how to use it.
You put a whole stack in one pocket. Then you don't even try to learn anything.
But when you wait in line for the cafeteria, you take one card. If you know the
answer you put it in the right pocket, if you don't know, you put it in the left
pocket. And you keep doing this, that's all. They creamed this exam, did
absolutely fantastic, and I got fired. [laughter]
But I must say, it was only the last straw. The thing that was really annoying
to them was that they thought I let everyone escape through the window from the
02:19:00lab section. The program manager would send in someone to bar the door because
he thought that since this is an army group, one should enforce army discipline.
We didn't have anything to do with the army, but he thought we should definitely
enforce army discipline. The bell rang at ten minutes to twelve. Some people had
finished the experiment at 11:40. I could see no special reason why they should
wait around on the floor for the bell, because then they had to wait an hour in
line for the cafeteria. They wanted to get in early to the cafeteria, and it
sounded reasonable to me. This guy in charge was not an army person either, he
was just in charge of this general chemistry course. He would send an assistant
to bar the door. So they had to sit on their bags for twenty or twenty-five
minutes. It looked like Napoleon's retreat from Russia. [laughter] We were on
02:20:00the first floor lab. So one day, somebody had the bright idea that they could
get out through the window. I thought it was hilarious; that's true. I thought
it was hilarious. It is not true, which they thought, that a) I had engineered
it, and b) that I had refused to tell them the names of the people that I knew
who went out the window. The truth is I didn't refuse. I did not give them the
names, but that's only part of it. I like to think that I would have refused
anyway, but the fact is there is no evidence one way or the other, because I
don't remember names. Particularly, I didn't know the names of these people. I
just didn't know them. But this was definitely viewed as a rebellion of the
02:21:00first magnitude. So by the time they'd got the best grade on the exam, that was that.
FINE: How is it that in the Wisconsin tome that was just published the history
of the chemistry department has almost nothing about Johnson and there's nothing
STORK: Because the author was quite old. I forget his name, but he taught a
course in the history of chemistry. I met him once. He was familiar with a much
earlier era, which is what he wrote about, although not very well.
FINE: Was that Aaron Ihde?
STORK: Yes. Well, he had no feeling for it, because it's not his area. I think
he said a kind word about Johnson.
FINE: Djerassi is almost totally ignored.
STORK: We did not interact with Ihde. I suppose as far as he was concerned, he
was old enough at the time and we were young kids getting a Ph.D.
02:22:00FINE: Just as an aside, was there anybody else at Florida, besides you as an
undergraduate in chemistry?
STORK: At the same time that I was there, there was some guy who became a stock
analyst for some company here. I forget his name. I saw him later, after I was
here, because he wanted to know what I thought of Syntex.
FINE: Did you tell him to buy it? [laughter]
STORK: No, I think I probably told him I couldn't say; he'd probably hold it
against me. [laughter] There was some guy who became a chemical engineer. There
was no one else that I remember. But I didn't interact with people very much, so
there could have been some pretty good people. I doubt it. It was not a great
school. There were some bright people there. One guy they can boast about is a
02:23:00Nobel Prize winner. Marshall Nirenberg got a master's degree there.
FINE: He's at NIH.
STORK: Is he at NIH?
FINE: Well, he was.
STORK: He got a Nobel Prize for the important work having to do with the genetic
code, and maybe related to what [H. Gobind] Khorana got the Nobel Prize for. We
didn't overlap; I didn't know Nirenberg. He was probably there shortly after I
was there. But there were not too many people. They were mostly people who would
go into agricultural things or engineering. They had a good electrical
engineering department--at least it was reputed to be a good electrical
[END OF TAPE, SIDE 5]
02:24:00BOHNING: You said you had gotten a phone call from Paul Bartlett saying, "Do you
want to come to Harvard as an instructor?"
STORK: I did that. [laughter] That turned out to be obviously very interesting
because Woodward was blossoming at that point. In particular, he had a very
rational approach to chemistry. This does not sound like a great accomplishment,
but at that time, most organic chemists were a highly intuitive group; that is
still true. But he was the first influential one to have had the article of
02:25:00faith that this somewhat amorphous intuitive feel was amicable to rational
processes. It sounds trivial, but it was, in fact, a departure.
It turned out to be quite nice because McElvain, believe it or not, was one of
the first people in this country to become interested in what was then called
the--what was it called?--it had to with the Robinson curved arrows. Robinson
did contribute a major thing here, whatever else he did or didn't do. It was
this electronic theory of the English school, as it used to be called, right.
The electronic theory of the English school consisted of at least the belief,
the underpinning belief, that there is some sort of rational thing underneath.
Even though Robinson himself, and again this is an outrageous statement, never
02:26:00understood how to use his creation; he just was unable to do it. People like
Woodward did. Woodward dealt with the Robinson conceptual framework much more
effectively than Robinson ever did. One of the first ones to introduce this in
the context of courses was McElvain, who actually was really quite fascinated by
this thing. He was not really as adept at using it in a complex situation as
Woodward was eventually. But he was fascinated by the underpinnings of it, which
he would tell people about.
It was also an interesting time because it was the end of the war, and a large
number of people of various age groups came back to Harvard, or came to Harvard,
which gave it a large diversity of people. There was much more of an age spread
than usual because some of them had been in the service. Harry Wasserman, for
02:27:00instance, was my age and I was an instructor and he was a beginning graduate
student. A lot of these people were really exceedingly good people, at a time
when it became obvious that organic chemistry had a future.
This included people like [Jerrold] Meinwald and [Franz] Sondheimer. [Eugene]
van Tamelen was one of my own students. They had lots of very good people there.
I mentioned Cram before. There were just a lot of people.
Huang Minlon was a postdoc. Do you know the Huang Minlon reduction? His name was
really Minlon Huang, but everybody's called Huang in China, so he inverted it.
02:28:00Huang Minlon was a postdoc of Fieser's. Mary Fieser used to delight in coming
sneaking behind him when he was working away in the lab, Huang Minlon, and
shouting something in what she considered to be Chinese and startling the hell
out of him. [laughter] There were large numbers of these talented people.
BOHNING: Elkan Blout was there. Was he doing his postdoc when you got there?
STORK: He was before my time.
BOHNING: Oh. He had left when you got there.
STORK: I knew Blout because we were very socially friendly with Woodward, so we
used to get together--Blout, Woodward and us quite often. Blout still is a
friend. He's still active. He's still treasurer of the National Academy.
BOHNING: Were you involved in the poker games?
STORK: No. The only time I remember a poker game is when we decided, and I can't
02:29:00imagine why, to take a train to a conference in Canada one time. It was on an
island called Grand Manan Island. I have a photograph of this thing. The only
one who still looks today like he did then is Nelson Leonard, which is really
quite amazing. Nelson Leonard is perpetually good-looking, young, dark hair;
it's just remarkable. And there was John Sheehan, Bob Woodward, Nelson Leonard
and I, on that train to go to the wilderness of Canada from Boston; it takes
forever. They decided to play poker, and decided that since there was me there,
it was an easy mark. The three of them were obviously old hands at this, so it
cost me a lot of money. [laughter] That's the only time I played poker for any
kind of money. Sheehan and Woodward would play poker. Woodward liked poker, and
02:30:00these other people are pretty good. Sheehan was probably the most adept.
[laughter] Woodward had no interest in sports. Poker was about the only thing; I
guess you would say it combined things that he liked. It was partially rational,
partially theatrical. He was pretty good.
There was nothing terribly eventful there, except that I had some extremely good
students, obviously. I didn't really realize I had, because that was the first
academic environment I knew. While I was at Wisconsin I really had nothing to do
with the people, except for Djerassi. My assumption was that this is a normal
group of people, but it turned out to be pretty exceptional.
BOHNING: One of the things I noticed is that up until this point your organic
02:31:00work was really classical in the sense that it was melting points, boiling
points, refractive index, and carbon-hydrogen analysis. But starting with the
Harvard period, in the first paper you had Elkan Blout doing your UV spectra
over at Polaroid.
STORK: I did?
BOHNING: You put that in as an acknowledgment.
STORK: Really? That I don't know about; that's interesting.
BOHNING: It's in the paper on sex hormones, which was the first one from the
Harvard period that I have. And in it you acknowledge Elkan Blout's assistance.
STORK: For UV? [laughter]
BOHNING: For doing the UV at Polaroid for you, because he was into that very
heavily at the beginning.
STORK: Oh, yes.
BOHNING: Then IR spectra started showing up in your work. There was quite a
difference in how you were identifying compounds.
STORK: That's normal. I would presume that 99.9 percent of people went through
the same thing because that became it. At Columbia, the person who first
mentioned NMR here was Louis Hammett. Louis Hammett once called me into his
02:32:00office and said, "I think we should do something about this new technique, NMR."
The truth is I knew precisely not what he was talking about. [laughter] So very
early he was sensitive to it. Woodward was sensitive to infrared. He was
obviously quite interested. Woodward's interest in instrumentation came from the
penicillin work during the war, where he was the first one to give a logical
argument for the -lactam structure. That was heavily based on work at Shell on
the infrared spectra of a whole bunch of compounds, which were -lactams. And
Woodward's belief, which was unusual and which was really faith, was that even
02:33:00though one could place some faith in these tools, so far as the organic chemists
were concerned, they were really statistical.
I still remember at Harvard taking an infrared spectrum, when the machine first
became available from an outfit called Baird Atomic, which still exists on
Brattle Street. The contraption was about that high [more than four feet] from
the floor and that big around [more than three inches wide]. It was a great
machine. It was the only machine I know that could be flooded and you could
repair it. One of my graduate students did that. Jerry [Alan Jere] Solo who is
the chairman of the pharmacy department at Buffalo, and he actually took it
apart and cleaned it. The prism was that big [five inches long], but it was
mounted on stilts, so you could fill that machine and not dissolve the salt
02:34:00prism. That machine was the first one at Harvard. It was there late because I
still remember having to go to Baird to take a spectrum with [A. W.]
Burgstahler, and that was in 1951. So it began to be available.
I was always taking infrared when it became available, but I took them myself.
[E.] Bright Wilson, the physical chemist whose son won the Nobel Prize, came in
and said, "What are you doing?" I said, "Oh, look, a carbonyl group." Pfffttt.
He looked at me as if I was completely insane. [laughter] He said, "How do you
know it's a carbonyl group? All you know is there's a stretching frequency at
this point. It could be carbonyl. It could be a peculiar double bond. It could
be any number of things." "Oh, we already discovered this." [laughter] Of
02:35:00course, what we mean by that is that it increased the odds that it was a
carbonyl group to ninety-six percent from an unknown number. By the time you
have seen quite a few of these things, there's a high probability of their being
true. Of course, Wilson was also right. But Woodward had that faith, buttressed
by the fact that he had seen all these other spectra. Penicillin was a difficult
situation where practically everyone, including the famous Robinson, was totally
antagonistic to that four membered structure lactam [of penicillin]. Woodward's
faith, based on the fact that you have to take things like infrared seriously,
was in fact correct. From there on you always paid enormous attention to infrared.
So the experimental chemistry changed. It changed for everyone, although, it
probably changed faster at Harvard. It's probably true that if you compare the
Fieser operation to the Woodward operation, there's no question that much
greater emphasis was put on paying attention by Woodward to tools such as
02:36:00infrared at that time than what was happening in the Fieser operation. They
would have paid some attention to UV, but that would be as far as they would go.
BOHNING: Isn't that about the same time that Woodward came out with those rules
for ,-unsaturated ketone.
STORK: No that was in his real youth.
BOHNING: Was that earlier? Yes, it was 1941 when he did that.
STORK: That's right. He must have been about twenty-two at the time of this
operation, something like that. These rules are interesting psychologically.
They're not particularly novel; even at that time there had been lots of British
stuff which was essentially the same. But it showed that he really believed it.
Also, there was a simplification in what he did. I mean, these advances are to a
considerable extent the ability to simplify; not so much to find out something
02:37:00necessarily that's particularly new, but to cut out what's important from what's
not important and go with it. That's an important ability that he had.
So that was my period at Harvard. Then eventually, of course, the question was
whether they would throw me out of Harvard or not. That's unlikely to be in the
BOHNING: I have a quote here from Fieser. It's in a
letter he wrote which states, "His departure from Harvard, although anticipated
and pre-scheduled, was a source of great regret to all of us."
STORK: Well that's certainly conceivable. Pre-scheduled was not totally correct.
It was a complex thing. Harvard at that time was the only institution in the
02:38:00country, which could afford, and still to some extent can afford, the luxury of
operating on a completely financially driven scheme. At that time the Harvard
endowment was constructed in such a way that every seven years a new
professorship would be created. If you didn't come into that operation, Harvard
could make an exception. I suppose, if [Albert F.] Einstein had been there they
might have. But they really didn't feel any great pressure to do that because
these were the days that if Harvard wanted Lenny Fine to go there, they would
just call up Lenny Fine and say, "We would like you to come," and you would be
on the train. [laughter] They could afford that scheme. In more recent years
they've found out that it's not always true, but now they're recovering it
because they've also found out that if you pay enough you can do it. [laughter]
Everybody has their price, which is not totally unreasonable. After all, why
02:39:00not? If you can do your work right.
So one component was that. It's also true that there could have been a
groundswell in my favor. There was, I regret to say, none whatsoever. The only
one who was favorable was, in fact, Woodward. But not enough to put his career
on the line, although he was genuinely sorry that I left. But the fact is that
Fieser, whatever this letter says, brought up my not quite correct melting point
of the hydroxycholesterol that I had given him. [laughter] If I had been
Harvard, I might have very well made that same decision. I think it was not an
irrational decision, given the entire sort of operation. The fact is Woodward
was doing pretty well. I wasn't doing something that is terribly different from
what it is that they were interested in at the time. And there were plenty of
02:40:00very good people, like [Elias J.] Corey, obviously a perfectly fine person (that
I'm not so sure about) and a perfectly highly competent chemist.
FINE: But he came later.
STORK: Yes. But eventually they were able to add somebody, and they didn't have
a crying need at that time. When they would have their seven-year itch, then
they would call some guy, and he would show up. Clearly, clearly, they may not
have got everybody they always wanted, but it is true that the people they got
were always extremely good.
There was the usual sort of terrible time that people go through which you
cannot possibly understand unless you've lived through it, of knowing a) you've
02:41:00got to find the future, and b) you have no clue what it will be. That is really
very difficult. That is a problem with the American system; it's also its
strength. It's very complicated. It is a reason we don't have people doing
structure or complicated long-term projects, but it's also the reason why we
don't have much dead wood. It's a complicated business, but in any event, it's
the system. So then I had to try and figure out what to do.
BOHNING: When did you know that the position at Harvard wouldn't be continued?
have much advance notice?
STORK: I would suspect they probably would do this thing the same way we do
now--probably a year. I came here [Columbia] in the middle of a year, about half
02:42:00a year before I would have to go someplace. That was majorly related to Jack
Roberts. I think it's true that Jack Roberts was the one who convinced them, or
at least made the strongest pitch in my favor. For some reason, I didn't ask him
to, but I knew Jack when he was the National Research Council Fellow at Harvard.
We had reasonable respect for each other. And I think he at least made a strong
suggestion to Hammett that this was something worth doing, and Hammett was
interested enough to ask me to give a talk here. They were sufficiently
impressed by my talk, for probably totally the wrong reasons.
FINE: Was Roberts at Caltech then?
STORK: Well that's something that one can establish. I came here in February of
02:43:001953 and I think he may have still been at MIT. He was probably still at MIT.
When I came here, I think Louis Pasteur's lab in Paris was probably no better
than the place here.
FINE: Nothing's changed. [laughter]
STORK: Oh, no. You'd be surprised. There were no hoods in the building here. The
only hoods there were, were these little round things on people's desks that you
see in some undergraduate labs. That was it. But the thing that's most
extraordinary, and although this has nothing to do with history, it's
extraordinary anyway, was the way the glassware was put in the desks. They had a
02:44:00rectangular section that was made of cast iron and had two trays that you could
access by pulling this contraption out, which was that wide [about one foot]. It
was not possible to pull it out level, because of the way the tongue and the
frame that supported it were off the floor. So it tipped forward, exposing
sideways the shelves on which the glassware was sitting. A fourth of the
glassware landed on the floor with each opening of this. So they were kept open,
because these things would tip over as you take them out. It was an enormous
thing; no woman could possibly move this thing. They would need help to do that,
with apologies to the weaker sex. [laughter] The fact is that you did it that
way, and then you left it open. So the thing was cluttered with these open
things, aside of which were these little so-called hoods on top.
There were no fluorescent lights. My first fluorescent light was a gift. A
02:45:00colleague of mine was George Frankel, who was a physical chemist in this
department. He is supposed to retire about the same time as I am supposed to
retire. He became dean of the graduate school eventually and now is again in the
department for a year or two. George Frankel had bought a couple fluorescent
lights, which he gave me. I had one fluorescent light attached with copper wire
to the steam pipe until the fire department came around and pointed out in
vigorous terms that this was illegal and I could not suspend electrical fixtures
to a steam pipe. [laughter] So that was the end of that.
My office had a distinguished history. It should be declared a national
monument, not because of me, but because of the previous occupant. My office,
652 Chandler, was the same office which Arthur Cope occupied [Doering also was
02:46:00in the office before me]. You really have to see it. It's about twice the size
of that desk over there.
FINE: By the elevator.
STORK: Yes. It now holds three refrigerators and it is full.
FINE: It's a closet. [laughter]
STORK: That was my office.
FINE: But you've been on the sixth floor the whole time.
STORK: Yes. The office I now have is at the other end of the corridor. I shared
the sixth floor with a physical chemist, who is a very famous physical chemist;
he has a prize named after him from the ACS, which is the Victor K. LaMer Prize
in Colloid Chemistry. He was the other occupant of that floor. Had no use
whatsoever for organic chemists; he hated them. He had a thick white line
painted on the floor, which was the frontier beyond which organic chemists were
not to trespass. Cope was only here one year. He was involved in war work and he
02:47:00worked mostly in Washington when he was here, so far as I can see, and then went
off to MIT. While Cope was in Washington, on one of his trips, LaMer decided he
needed more space. He took out all of the equipment of Cope in a couple of the
labs, tossed it out in the corridor, and put his people in. Presumably it is no
longer done that way. [laughter] Then had this white line painted to boot.
[laughter] So Cope told me, "I'll give you only one piece of advice. Stay away
from LaMer." The next thing I know, I'm sharing the floor with LaMer. [laughter]
Well, I actually enjoyed LaMer. Although we never got along in the classical
sense, nevertheless I had affection of a kind for LaMer because he was a spunky
little old fellow. He cared about what he did. It was possibly silly what he
did, but he cared a lot. He was really enthusiastically teaching his students
02:48:00that all that people wrote on thermodynamics was wrong, because they didn't pay
attention to his stuff in a proper way. But he did it with gusto and enthusiasm,
and he really cared about it. Eventually, he died of a heart attack on a dancing
cruise, having taken up social dancing at the age of sixty-something and was
fascinated by it. [laughter] So that was the situation here.
Frances Hoffman originally came from Harvard with me, then eventually decided I
didn't pay her enough and went off to Merck for seven years, before she came
back as the director of laboratories here. When she became director of
laboratories, they redid the floors in various sections. By modern standards, it
really looked awfully crummy. But there was a major departure from what existed
02:49:00before, since there was in fact nothing there. That was done under the
chairmanship of Ralph Halford, who was a physical chemist who was majorly
involved in the eventual design of the Perkin-Elmer infrared instrument.
[END OF TAPE, SIDE 6]
STORK: Halford eventually became dean of the graduate school. The labs that were
produced then were more or less feasible. Breslow's office was 552, the same
damn set up I had--the refrigerator room. But that place originally had Cope in
it. It was Doering's office and my office. That's pretty good! That's a pretty
good succession of people. I don't know who was in Breslow's office before him;
probably very good people, too.
FINE: Doering was in 552, too, before Cope?
STORK: Was it before Cope or after Cope? I think it was before, no after Cope.
Then he went off to Yale.
BOHNING: Doering tells the story that he wanted to get an IR, but Hammett, who
was chair then, refused to get him one. But Hammett
agreed to get you one. Is that true?
STORK: Oh, the IR, yes. I don't have any great merit for that. There was a
professor of organic chemistry here at the time, who is still alive; he's
retired and lives in New Hampshire. That's Charles Dawson, Charlie Dawson.
Dawson is the one who wrote me before I accepted the job here. He said, "What
you should do is to make your accepting the Columbia's offer contingent on
getting an infrared machine in this place." [laughter] It was his suggestion; I
would never have thought of it. So I did that, and we got our first Baird
infrared machine as a result of this operation; It was not a total gamble on my
part, since there was an inside person here who was suggesting it. That's when
we got the first one.
As I said, later Hammett was the one who initiated that we should get interested
in NMR. He convinced Benjamin Dailey, who just retired a couple years ago from
the physical chemistry group, to become interested in it. Dailey was ready to
have his arm twisted because he was veering in that direction anyway. Dailey did
some early work. He had a very important paper with the person who did some of
the early NMR development, [J. N.] Shoolery, correlating chemical shifts and
structure; it is an important paper.
So that was introduced here, but Columbia was not at the forefront. It's a small
place. Columbia has a difficulty in that it's expensive to do research, and it's
clearly getting more expensive all the time. When I was a graduate student at
Wisconsin, you had to make a reservation to use the Beckman manual DU
instrument, two or three days ahead, so they could arrange for a member of the
professorial staff--in my case it was Al Wilds--to go with you and sit there or
come back every so often to see that you didn't damage the instrument as you
spent two hours to do point-by-point spectra of some damn molecule. That was the
sum total of the instrumentation at Wisconsin.
Eventually, towards the last two years of my stay, there was the infrared
machine at Harvard, and there must have been a UV machine somewhere, but I don't
remember seeing it. It was probably automated by that time. Then here there was
not a damn thing, except for this infrared machine; eventually they got
something. But it's difficult; it's expensive and the place is small. The place
is small and therefore the cost per person, or recovered overhead or however you
want to put it, is just small. So it has never been the leader in having
instrumentation in the place, but it became more or less adequate. On the other
hand, the Varian instrument that we got, the A60, was the third in the country.
It was the third such instrument, the Varian A60, so we were getting there at
BOHNING: What kind of a chairman was Hammett?
STORK: Actually, the chairman when I came was probably not Hammett but Arthur
Thomas. Well, maybe Hammett had just became chairman. That's possible. Yes.
Actually, Hammett was chairman before I came because I still have handwritten
letters of Hammett, which I've never used as a weapon or anything because I
didn't have to, which say that I would never have to teach an undergraduate course.
FINE: But you have.
STORK: Yes. I thought it was kind of silly. They also said that I would not have
to teach in the evening. I did both. I don't know. [laughter] That's irrelevant.
So he was chairman, but before that Thomas was chairman; he was obviously
hopeless and disastrous from everything that I know about it. Hammett was a very
fair chairman. He was difficult to approach. I don't know where I get these
stereotypes, but I always thought of Hammett as a rock from Maine. But he was
not from Maine. [laughter] But he was a sort of a rock, and it took me years
before I could call him Louie. In fact, I did this only after repeated
entreaties. Hammett was Professor Hammett and that's all there was to it. It was
just that way, because he did not fool around easily. He was a little bit
related to McElvain, in that sense.
Hammett was doing his best for the department in days that were fairly
difficult, earlier on. He had a very important role in building the department.
The one example that some people know (and I don't whether it's in here or not),
is how we got [Ronald] Breslow here. Without Hammett, there wouldn't have been
anybody with some sense of humor and more than sense of humor, and we would
never have gotten away with it. What had happened is that I knew Breslow when he
was an undergraduate at Harvard. In fact, he did his first two papers with me on
the structure of a compound called cedrene, the stuff that makes cedar closets
smell like cedar closets. It actually was an
important paper, because it was the first paper where there was actually an
effort to correlate certain features of infrared with structure, specifically
the difference between five and six membered cyclic anhydrides. It was the
crucial clue to the structure of cedrene.
So I knew Breslow was an extremely bright guy. At that time he was a postdoc for
Todd in England. He had been offered a position at Wisconsin, and I wrote him
and said, "You really should forget about Wisconsin. You should come here." You
know the way departments move. You've been around enough to know that this is
not necessarily the fastest operation in the world. At that time, this place was
sort of a frozen mastodon. So circumstances arose that I had to send a telegram
to Breslow that we offered him this position, before discussing it with my
colleagues. [laughter] Now, one should not do that, and I'm not advocating it at
all. It just had to be done that way. It was a gamble that I would then be able
to convince my colleagues.
So there was a department meeting. Things went slightly wrong, in that Breslow
wired back a telegram to the chairman, Louie Hammett, accepting the offer.
Hammett had not opened the telegram before the meeting. He'd collected together
departmental stuff and he would open these letters and read them to the staff.
And I didn't know anything about the telegram. Then he opened this telegram.
When Hammett got a little excited you could see red climbing up the back of his
neck. He was obviously getting somewhat excited as he read this telegram, which
said, "Pleased to accept your offer of the instructorship." Of course, he's
saying, "What does this mean?" "Oh," I said, "I'm sorry. This has no meaning.
It's just a code, that he was supposed to wire back if he would accept it, if we
decided to offer it to him, so we can save time." [laughter] Hammett said, "Oh,
I see." Although we never talked about it, it was perfectly certain that he knew
perfectly well the kind of skullduggery I'd been involved in and went along with
it. So Breslow came. That was pretty good.
BOHNING: Had you had any other offers, or looked at any other places before you
came here? You said that was sort of a traumatic period.
STORK: There was maybe four months before this thing came up. I am not sure, but
there is nothing that I can remember, and it may very well have been nothing. It
was all fairly tentative, and this one was the first one that was a real
something. I happen to like cities and so the fact is New York sounded like a
very good thing to me. I don't think I fooled around very much except for asking
for this infrared machine. There was no game playing.
I lived in an earlier generation. I have nothing against game playing. It's
rational. Baseball's a perfectly good sport, and we're moving towards the
baseball operation. Well, not enough. I believe we should adopt one more thing
from baseball. Let's see. We stole [William] Clark Still from Vanderbilt. Now,
that's really not nice to Vanderbilt. What's the incentive for a place like
Vanderbilt to develop and treat young men very well? Or, let's say Michael Kahn
is at the University of Illinois, Chicago Circle. There's absolutely no question
Michael Kahn is going to be out of there within a year. Now, they spent over a
million dollars on Michael Kahn. He's brilliant; there's no question about it.
So this should be the same as what baseball used to do; I don't know if they
still do. You pay something to the club to get this guy. I think that's
reasonable. Then it gives them incentive. Otherwise, what's the incentive? They
get burned a couple of times, and the incentive to get someone who's better than
they can afford is not great. It's a very serious problem.
FINE: We've been a training ground for a lot of other schools.
STORK: Yes. Almost by definition, this is not a bad place, so obviously they've
got to go somewhere else that's outstanding; it's going to have to be at least
as good as here. But you certainly could make a stellar department out of the
people who are no longer here. There's no question about that. Which is, of
course, probably true of a number of places.
So Hammett was sensitive to things. Hammett was succeeded by a nice gentleman
named [Charles O.] Beckmann, who had not done any work at all for years; he was
a physical chemist. Charlie Beckmann had done some early ab initio calculations
of the rotations of evantiomers of certain chiral ketones. The effort to do this
just simply convinced him that there must be easier things to do than continue
research. He was a plausible chairman, although Hammett thought he was a total loss.
Eventually, the department passed a rule that the chairman could not succeed
himself and could only serve for three years, obviously exempting the incumbent,
who was Beckmann. As a gesture, we were hoping he would volunteer that this
would apply to him as well, which he did. So everybody was satisfied. But,
unfortunately it produced what I think is a bad system. It produced a system of
compulsory automatic rotation, every three years, which insures that a new
chairman doesn't know what's going on for one year, can do something for one
year, and is a lame duck for one year. It is not a good system. It is maybe a
humane system, because it's also true that that job would kill most people. It's
not surprising that for a long time, whoever was chairman of the department
stopped doing anything afterwards. In more recent times there were more and more
exceptions with this forced rotation, otherwise nobody would be doing anything.
But there are obviously problems with that.
BOHNING: You were still at Harvard when you made the Syntex connection, through Djerassi.
STORK: Yes. The Syntex connection was really Djerassi convincing me to consult
for Syntex when it was essentially a garage. I was very much involved with
Djerassi and what was going on there. Much of it was by phone, and I would also
go down there. In those days it took forever; they used propeller planes, so it
took fourteen hours to go to Mexico. Not quite that, but almost.
BOHNING: Djerassi has said that when he went to Syntex in 1949, you told him he
was stark raving mad. That's his quote. He was at Ciba, wasn't he?
STORK: He was at Ciba. Did I say that?
BOHNING: That's his quote.
STORK: That is conceivable. That certainly would be a reaction I could easily
imagine that I had. I don't think I was strongly against that. I think I
probably would have said he was stark raving mad. On the other hand, he wanted
to talk to Max Tishler, who was at that time the industry-university connection
statesman. I'll always remember what Tishler told him. The president of Merck at
that time was George Merck. The president of the United States was [Dwight D.]
Eisenhower. The president of Syntex was George Rosenkranz. What Tishler said was
ridiculous. He said, "Syntex is just a nothing operation. When the president of
the United States wants some advice, who does he call? George Rosenkranz or
George Merck?" [laughter] That was supposed to be a serious point. Djerassi had
the good sense, I guess, of paying no attention whatsoever and taking off for
Mexico, which took a lot of guts because he didn't speak Spanish, among other
things. It took guts of various kinds. At that time I was pretty much involved
with Syntex, which was kind of an interesting operation. Djerassi only stayed
there about two years. Then, we both consulted for Syntex and we used to go
there together, which was really a very good consulting system because we'd
fight and argue without any barrier. That produced much more interesting
chemistry than just the formal endeavor that sometimes passes for consulting.
BOHNING: You said you went to Mexico City several times?
STORK: Yes, I would go maybe three or four times a year.
BOHNING: What kind of operations did they have when you first started going there?
STORK: They had a pilot plant, which was not trivial. There were several
Pfaudler kettles. They were not clean by today's standards, but very plausible
by Mexican standards. They had research labs with no hoods, so they did some
things outside on the patio in twelve-liter flasks (some were twenty-two-liter
flasks), brominating stuff into the atmosphere. [laughter] Even in Mexico, I'd
think you'd have a tough time getting away with that kind of stuff today. They
were very primitive operations. There was an old munitions factory, called
Molino de Bezares, which they had and in which they were doing things. They were
mostly extracting raw material following Marker's initial discovery that a good
source of something which you could sell to make progesterone was this thing
called cabeza de negro, black man's head or Negro's head, which was a root from
which they extracted stuff. So it was mostly doing extractions. They also made a
few witch-doctor type of medicines for the Mexican or South American market.
Rosenkranz majorly changed it. Both he and Djerassi were of middle-European
origin. He recognized that Djerassi was a powerful person and the person that
they needed. They hit it off well. At that time Rosenkranz was working in the
lab himself with an assistant. Djerassi was also, and they started doing well.
The view of the outside world, like people at Merck, was "Of course they did
well. They had no restraint, no restriction on publishing stuff. They had no
patent problems, no patent department." Of course, these other pharmaceutical
industry groups were frustrated as all hell because a certain percentage of the
work Syntex published, which could have easily have been ninety percent, they
had done before, but they were not allowed to publish it. So Syntex was always
first in publishing it. Syntex did nothing wrong; on the contrary, it served to
loosen this straightjacket that they operated in. But it did not contribute to a
friendly relationship, obviously. Although Syntex was often accused of shady
practices or borderline operations in the early days, there's never any actual
case of that that I ever knew of. It was perfectly straight; they were making
money by selling stuff that people wanted to buy, that's all.
Little by little they became known because they published all the time. That was a
BOHNING: I think you had at least three papers during the Harvard period with
Rosenkranz and Djerassi.
STORK: These were gestures on their part. This used to annoy me. They would do
this as a friendly thing. One of them I had something to do with, another one
they put my name on it, and one of them was embarrassing because nobody could
repeat it. It turned out to be an important paper. There was recently a
multi-million dollar patent case in which I was involved until they decided I
would make a terrible witness. [laughter] It's a side chain hydroxylation of the
corticoid hormone, the dihydoxy acetone side chain, so-called. Progesterone
doesn't have a terminal hydroxyl. The question is how can you stick these
hydroxyls on there, and so I suggested this, they put my name on the paper, and
it worked! I didn't really think it would work. They put my name on the patent.
Then this gets published, and nobody can repeat it.
I remember Bill Johnson making a public statement about it at an ACS meeting,
that people shouldn't publish papers unless they give all the details, because
nobody could repeat this stuff. I didn't even know at that time that my name was
on the paper. It turned out that it actually is an interesting story. Everything
that was said in the paper is correct. The reaction was done in tetrahydrofuran.
It turns out if you do this in absolutely pure tetrahydrofuran, it doesn't work
at all. It turned out it's essential that this pure tetrahydrofuran contain some
peroxide. The operation was conducted in Mexico and the tetrahydrofuran
contained plenty of peroxide. Probably it was not even distilled. Or maybe it
was distilled, but it still contained peroxide.
Eventually somebody realized that. It was not a question of malfeasance; it was
a question of not realizing the essential presence of a small impurity. The
patent about putting in the oxygen at C-eleven is one I definitely did. There
was a Life magazine picture, which was a great picture that I have framed at
home. It's a picture of the research group, with
Rosenkranz and Djerassi; I'm in there at the blackboard. This picture is about
putting the C-eleven hydroxyl group in. That was very nice chemistry. You could
still do this as a problem.
It's amazing about organic chemistry. The advance in organic chemistry has been
absolutely spectacular, but it's hard to tell. The way you can tell is that no
one in his right mind would have considered making a compound like erythromycin
thirty years ago. I don't mean succeeded in making it; nobody would have
considered the possibility of making it. Out of the question. Today people do
this until you're bored to read this type of thing. I mean, there's another
description of another damn macrolide antibiotic synthesis that someone made by
controlling this aldol or not controlling this aldol. Who needs it?
That implies an extraordinary difference. You know, in the same sense that it's
totally boring to read the paper that somebody's making some
oligodeoxynucleotides with his machine, a machine that makes things while you
sleep. It's boring. But the fact that it's boring is exciting. [laughter] It's
extraordinary. This is what happened in organic synthesis. But it happens in
ways that are incremental. The glacier analogy is the one I like; that is the
glacier obviously doesn't move. If you put a stick in a glacier and come back
six months later, it obviously has moved. But you can't see it. This is the way
organic chemistry has progressed: the advance is spectacular. It's really
spectacular, but it's easy to see only from what you couldn't do.
The Woodward-Hoffmann rules may very well be an exception to this. That's an
event, which you can date, where at one point something is recognized that was
not before. But that kind of thing happens damn infrequently, and the general
progress is not something you can time and say, "Oh, such and such year is the
year that they controlled the aldol condensation." It's not that way. But the
net result is you know how to control it now to a great extent. Whose work is
it? Well, it's probably [Clayton H.] Heathcock, probably [Satoru] Masamune,
probably David Evans. This one is contributing this, this one is contributing
that. The whole thing is put together by someone else who himself didn't
contribute very much except to put it together.
One of the phrases that grates me is, "I don't want to do just synthesis." Just.
People are now taking it essentially for granted like oligonucleotide
construction. It would be a reasonable thing to say. "I do not want to do just
oligonucleotides" would be perfectly rational. But it isn't that way at all,
yet. Even though there has been an extraordinary explosion. You pick up any
journal thirty years ago, in the Fieser days, and it is dull, it is terrible.
You pick up any lousy Tet Let [Tetrahedron Letters] today, and if there are not
two articles that are exciting in there, it's surprising. There is just a lot,
and it's not just the U.S. There's a major amount from Japan, once in a while
from Korea. Once in a while a guy in Bangkok is publishing clever stuff. There's
just simply an awful lot of very, very good chemistry. But none of it is
dramatic per se, it is dramatic in totality.
BOHNING: How did you select your ideas? Is there a common thread to how you
developed them? As I look at your list of papers, it's the total synthesis of
this, the total synthesis of that.
STORK: Total synthesis and methods for total synthesis.
BOHNING: But there's such variety involved.
STORK: The thread is clearly a three-dimensional construction, and that means
natural products. I don't know anything about natural products. A real natural
chemist would be Koji Nakanishi. Indeed, he understands something about natural
products, where they come from, cares about their structure, wants to find out
about them. I don't know. I practically never see an actual natural product. If
we succeed in synthesizing something, by that time there's just enough for an
NMR. So why natural products as targets? Partially, it's material motivation.
You have to get some money for this stuff, so you have to pretend for the NIH,
with the understanding that it's not true, your work is related to something
biological. You want to get a grant to make this digitoxin they were talking
about, which we did in fact succeed in making recently. But fortunately there
have been enough biologically active natural products that could be snuck
through the NIH door and also have an interesting shape and raise interesting
structural problems. The way I get interested in a particular one is difficult
to say. I'll give you one example and it's the most recent thing that we're
really very much interested in; and so is half the country at this point. It's
taxol, for the obvious reason that taxol is a structure that's pretty
complicated; very complicated, but not impossible. Everybody's excited about it
because it's the only drug that has shown major effects in some solid tumors.
[END OF TAPE, SIDE 7]
STORK: I have two very good people working on taxol now. We're about five years
after everybody else who is working on taxol. [laughter] I didn't even know the
thing existed two years ago when Ayako Yamashita came here. She was a
professional chemist who was working at Upjohn, and got an Upjohn sabbatical.
She wanted to work on something. I was desperately looking for a slave because I
wanted to make oligonucleotides for some special reason which has potentially to
do with cancer control, but it's a minor operation. I couldn't convince anyone
to do that. People who come to work with me obviously are biased towards what
they think I'm supposed to be doing, and they don't want to make
oligonucleotides. So I said, "Do you want to do that?" And she said, "No.
[laughter] I want to work on synthesis. Why don't you look up taxol; it's a
problem a lot of people are working on. It's really quite an interesting problem."
She started working on taxol; she worked on it for a while, and then went back
to Upjohn. But then I became more and more interested. But the interest is
always the same. That is, there is a target, which is difficult enough that you
can see some problems you don't know how to solve, but you see a kind of
possible solution; and then you get into it. Simultaneously this leads to
working on methods.
In that sense what we do is really very different from what I see Woodward did.
I have a statement about what Woodward did in synthesis that I've got to make
because I want it on tape somewhere. I said this to Arigoni, and he locked
himself up in a fit of anger in a hotel room for an entire day before he would
consent to emerge. Arigoni worshipped Woodward--it's a religious thing; I don't
know why. My statement was that Woodward contributed nothing whatsoever to
synthetic methodology, with the exception of some reagent which Aldrich peddles
as Woodward's reagent. There are two of them, Woodward's reagent K, and who
knows what other one, which are not much used by anyone making peptides, but are
supposed to be useful to make a peptide bond. There's no one I know of who ever
uses them. Okay. Nothing else, is my claim.
Now that's an outrageous claim to anyone who's brought up with organic
chemistry. It happens to be a correct claim, which I can defend any time anybody
wants to hear about it. Woodward was so brilliant. It's like a great composer
who does not necessarily have to invent half tonalities, or who knows what else.
There are some notes out there, and if he's brilliant enough, he can do
fantastic things with that. Then after that, who knows? Nakanishi may not have
invented his card tricks. There's no new mathematics coming out of Nakanishi's
card tricks, but they are damned impressive. That's not too bad an analogy; a
better analogy would be mathematical puzzles. You probably don't create new
mathematics by solving them, but there certainly are people who are brilliant
enough to find solutions to these things by manipulating known things. You have
to see how they could be done.
Woodward could do them, but there is almost no new reaction there. When people
think it's a new reaction, what they're saying is that their knowledge of
chemistry is not good enough to see where Woodward got that. But I usually would
know. [laughter] The fact is that he did not create new synthetic methods. He
was not interested. He was not consciously not interested, but he just didn't
need it. He was able to find his way with what was available. It's a different
case from George Büchi, who was violently against developing new methods,
although he did introduce things that were really very novel; several were
really novel and extremely exciting. He did it, but he didn't want to. He was
perverted in a sense by Woodward; if you're brilliant enough, you ought to find
ways out, using what exists.
We don't have that kind of a hang up. We have worked on both; the structure
suggests that there's a need for finding a way of doing this, and sometimes we
succeed in finding it. Some of them are showcases. There is one of the syntheses
I'm reasonably proud of. To my surprise, there was recently an event that I
didn't know was going to take place during a meeting in Minneapolis, where they
had found some people to say more or less nice things about my scientific
career. One of them was [Samuel] Danishefsky. Danishefsky came with slides,
which he had made of what he thought were the most interesting things that I had
done. The interesting result of that was that I was both interested and annoyed.
For the obvious reason, if you're a psychologist. I was annoyed because he
didn't pick Q, R and S, which I thought were great stuff. How come he didn't
pick that? [laughter] On the other hand, he picked some other stuff that I
thought was really not that great.
It was interesting, but the fact is that one of the ones that he did not pick,
which I thought was really very good, is the lupeol
synthesis. Lupeol is a triterpene, which has ten
asymmetric centers, or something like that. It was totally constructed by
methods that we had developed. They did not exist before we did it. It is
something called the regiospecific formation of enolates. You want to do the
reaction at this point, not at that point, on that side of the ketone, not on
that side of the ketone. How do you do that? You've got to solve two
problems. One is, you have to generate this enolate rather than another enolate;
it's this enolate, not that enolate. You have to find a way of doing that. And
after having generated it, it has to be of such a nature that it does not
equilibrate with the other one faster than you do something to it. We solved the
first one by showing that lithium enolates could do that; we were the first ones
to do this, although most people don't know that, with a paper with [S. D.]
Darling and [Jiro] Tsuji who became a major figure in Japanese
chemistry. About every step is, in fact,
regiospecific generation of an enolate, and a construction using it.
So we like both methods and total synthesis. The origin is the structure, and
the structure needs methods. Not the method first and then the structure.
Structure, problem, method, back to structure. It's kind of a sculpture. It's a
challenge. Everybody gets interested; as soon as you can make a problem of
something, it becomes interesting. Whether you're a chess player, or whether you
try to find a way of preventing paper bags from falling apart when they're wet.
If you can make it into a problem, it becomes interesting. As I said, I'm not
mathematically inclined. So this shuts out thirty-five percent of what you can
possibly do. Well, that's nice. Thirty-five percent. [laughter]
BOHNING: Did you and Woodward discuss mutual ideas in synthesis?
STORK: Yes. In fact, there was one time when we had to get Paul Bartlett to
adjudicate which one of us was allowed to work on this synthesis problem. It
turned out to be santonin, a famous sesquiterpene lactone. We both independently
decided it might be a nice problem to work on. I wrote up my scheme, and he
cooked up his scheme; they both used the same clever trick. [laughter] So we
went to Paul Bartlett and said, "You should decide which of us is allowed to
work on this." I forget what the decision was. The net result is that we both
abandoned it. [laughter] So yes, we would discuss things.
I don't know why I happened to think of this now, but Harvard had a rule that
instructors could not have graduate students of their own. It was the first
academic rank, but different from the present assistant professorship. Of
course, there was no external source of funds in those days. I got my first
research money from the Research Corporation, when we became interested in the
cortical hormones. We convinced them that what we were doing had something to do
with it, and they gave us some money and they gave some money to Woodward also.
But there were no NSF grants, and there were no NIH grants, at least for
chemists, at that time. The students paid for their own chemicals and you did
the best you could. Mercifully, there was no Aldrich, so you didn't have to
spend all your money buying chemicals.
So I couldn't have any graduate students. My scheme was to make estrone, which
is what I had started working on before at Lakeside. I had one really
interesting feature, and Woodward thought it was pretty good. Woodward was
pretty young; he was only five years older than I was. When I started at Harvard
I was nearly twenty-five and Woodward was about twenty-nine or thirty, something
like that. At that time he was driving a Packard; he should have kept it. He was
driving a Packard, one of those things with a rumble seat. [laughter] The color
of this thing was absolutely indescribable. It was majorly lavender, but with
patches of yellow, and non-glossy. The right fender was held together by copper
wire to the rest of the body. I still remember sitting in this car in front of
25 Follen Street, which was a group house that my wife and I rented with
thirteen other couples. Housing was extremely difficult to get at the time
around Cambridge in 1946, when I showed up, so we shared that place, which had
one kitchen and two bathrooms, with thirteen couples. They were various graduate
students and what have you. We were sitting in Woodward's Packard, because he
was taking me back to Follen Street after an evening seminar. He offered me this
deal that he would let me share three of his graduate students if we both worked
on my problem. So I said, "This is a great deal." The truth is this deal was
very much more favorable for me than for him, because I didn't have any graduate
students at all. So I would get a share of these guys. There was Aaron Nelson,
Bob Wineman and Aksel Bothner-By, who became famous in the NMR field by
designing the first 600-megahertz machine. So I had a fifty- percent ownership
of those three guys and we were going forward busily.
Woodward contributed majorly to the operation. My scheme was a sort of
Diels-Alder scheme. It doesn't matter what it is, just a plus b. The b part was
the right hand side of the molecule and was supposed to be a precursor of the
C/D rings. My part was to do the ABC construction after the C/D rings had been
put together. Woodward convinced me, quite correctly, that my dienophile was not
really designed as well as it could be, and that his dienophile was better,
which was probably true. So we embarked on this project and things rolled
Incidentally, and whether anybody believes it or not is not really important, so
far as I'm concerned it was the first time that Woodward was made conscious that
it was in fact desirable to control asymmetry in a molecule and it was possible
to do that in this case. So the thing was designed to be completely
stereospecific. It went on to the point where the last thing to do was to close
the diacid to make the cyclopentanone D rings. The diacid was a highly
crystalline solid, and that compound had previously been made in a non-specific way.
We got that compound, and it had exactly the same melting point as the
previously made compound. Let's suppose it has a high melting point, maybe 240
degrees, really pretty high, and nicely, highly crystalline. We get that
compound, and its melting point was exactly what it was supposed to be. So we
concluded that our synthesis had been successful. I got a phone call in the
morning from Woodward; he said, "Would you mind if we meet in my office this
morning at ten o'clock, because the director of research of Ciba is going to be
in town, and I would like to tell him about our estrone synthesis." Fine with
me. So we met there with a guy whose name I forget--it starts with a P
[Plattner]. Woodward was a theatrical person. I was sensitive because Woodward
was Woodward, and I was--who knows. Automatically, he would get the limelight.
Because this was our joint operation, I'm necessarily psychologically slightly
disturbed by what goes on; nevertheless, I'm there because he knows that I have
to be there. But he doesn't mention me at all. He describes in elegant terms
"the" synthesis; he doesn't say "my," he doesn't say "our." It's "the"
synthesis. But the implication is that it's his synthesis. So I'm tense, and
somewhat resentful. You wouldn't believe it--he goes through the entire thing,
and the Swiss agree to send him a sample of the real McCoy, so he can do the
only check possible at the time, a mixed melting point.
So the chemical appears from Zurich, and it melts like our synthetic diacid.
Woodward, with total drama, demands that the laboratory bench be covered with
white sheets, because the lab bench was not clean enough for the conclusive
mixed melting point. It would have been the first stereospecific synthesis. It
was a big deal. The melting point apparatus was put in the middle of the bench
and he goes in to take the mixed melting point. At that point I can't stand it
any more. I leave and go to Harvard Square for a cup of coffee. When I come
back, there is gloom all over the place. [laughter] My feelings are mixed. I
must confess, to my possible shame, that I had mixed feelings. I was not unhappy
that the whole thing had screwed up because I knew that I wouldn't get any
credit for it whatsoever. [laughter] In fact, the melting point was depressed
some forty degrees or something like that. It turned out that the Diels-Alder
reaction, for reasons, which are yet not clear, instead of going the desirable
way, had gone upside down. So our methyl group, which was supposed to be up
there, was in fact down there, and by extraordinary coincidence, these two
acids, the right and the wrong have the same melting point. The reaction was
completely stereospecific, all right, but it was upside down. [laughter] So that
thing that is published in Experientia is incorrect, but also it was done
without asking Woodward at all about it.
How did I get into that? I don't know.
BOHNING: We were asking you about Woodward and your conversations.
STORK: Yes. So chemically we had a very close relationship. Whenever Woodward
was in town, we always had lunch together. And sometimes when he was not in
town, we would actually go somewhere together. It was quite close, but only
until the end of 1952. It was about six years, but that was before his major
synthetic accomplishments. His major synthetic accomplishments were in fact
reserpine and strychnine, and that was done after I had left. Reserpine not long
after, although it had started before. Strychnine had been started before; this
was a major, major contribution. Woodward's steroid stuff, the world considered
major, but it was not. It had lousy stereochemical control. The one that he did.
After the joint synthetic fiasco I mentioned earlier, we worked independently.
After that I was promoted to what was called an assistant professorship, which
was like the second term of an instructorship in places that have three plus
three terms, like Yale, for instance. At that point I could have graduate
students, which is when people like van Tamelen and then Dick [Richard K.] Hill,
who became a professor at the University of Georgia, and other people like Leon
Mandell, who became the dean of science at the University of Southern Florida.
But before that I didn't have any students, except those three fifty percent
This may have been very influential--Bothner-By may have given up organic
chemistry because he was disappointed with that project; but this turned out to
be to the great benefit of NMR people.
BOHNING: What about van Tamelen as a student?
STORK: Van Tamelen's a smart guy. By today's standards, somewhat dilettantish in
chemistry. He had done very nice undergraduate work at Hope College in Michigan.
He was a Michigan kind of person, a tulip person. His great ambition was to find
out what made tulips colored until he found out somebody had already done that.
It turned out it was wrong. The matter of the coloring pigments of flowers is
really a complicated thing. It's essentially known, but everything that one
believes about it is incorrect. All of these compounds to which the colors are
ascribed are artifacts of the isolation operation. The real thing is just
unbelievably complicated. But anyway, he was a tulip person, and he had done
some undergraduate work at Hope College and started to work my cantharidin
synthesis. He made desultory progress; there's no way that the cantharidin
synthesis would have been completed, except for [Albert W.] Burgstahler.
Burgstahler was an experimental wizard of the time. He'd be wasted today.
Burgstahler could make anything crystallize that he dealt with. I still have
boxes of samples from Burgstahler, nice, beautiful, crystalline compounds.
Nobody knows what a crystal is anymore. Chemistry is an intellectual thing now.
Now you look at a peak in a spectrum; it's very analytical. You don't often get
the thrill of making crystals, which Woodward felt more than most people. That
was not put on. There was a real feeling of joy at the crystal, the crystal
shape and coloring and that sort of thing; there's no question about that.
With Burgstahler, this was the time that people took three years to do their
Ph.D. degree. Burgstahler was such a great experimentalist. He finished
cantharidin on July 4th, 1951 at four o'clock in the morning. I know that
because first, it was Independence Day, and secondly, I was supposed to catch
the plane to Mexico at seven a.m. Thirdly, we finished the synthesis at four
a.m. I know, because I was there to provide moral support. Burgstahler was a
fervent Catholic who, every half-hour, would go up to the roof of the building
to sing a Gregorian chant so that the final product would crystallize.
[laughter] It was an impressive display of the effectiveness of faith, because
it did crystallize, and therefore this was great. The fact that was possibly as
important was that he was a brilliant experimentalist. And so, we made
cantharidin. I drove to the airport, picked up my plane to Mexico, and that was
pretty good. [laughter] It was incidentally, the first planned stereospecific synthesis.
Van Tamelen started this thing, but did not really make all that much progress,
although he was a very, very good chemist and did brilliant work later. Van
Tamelen's career, from the chemist's point of view, is a shame, because he gave
up when he did, when he could have continued for another ten years. From his
point of view it's only a partial shame, because he made millions of dollars in
real estate. Part of the time that he was spending on his real estate operation
was interfering with his chemistry. Whether he would consider it a catastrophe
that he retired to take care of his holdings, I doubt. [laughter] I doubt. He
had a very fine career. He was one of the best chemists in this country in what
Both he and Johnson became interested in different aspects of the same
fundamental operation, the polyene cyclization business. I was once asked by
Djerassi and Calvin Stevens (who just retired from Wayne State) to join them at
Wayne State. We were all three friends and Calvin Stevens was also at Wisconsin
working for McElvain at the time Djerassi was there working for Wilds. We were
all together. My point was that even if I had wanted to go to Wayne State, I
happen to value their friendship, and there's absolutely no question in my mind
whatsoever that if all three of us went to the same place, that would be the end
of it. Forget it. [laughter] But Johnson and Van Tamelen faced that problem.
They were very good friends, but eventually they would only write letters to
each other through the Post Office, even though they were only two doors apart.
That's what happens. Obviously it could be the same woman; in that case it was
not very different, it was the same problem.
BOHNING: You mentioned this polyene cyclization, and there's the
Stork-Eschenmoser hypothesis, which came around 1950 and which deals with that
area as well.
STORK: Yes. There's a symposium that's taking place in New York at the end of
August, that has do with this. Konrad Bloch is giving a talk, and it would be
interesting to see what he says about it. This is a complicated thing, the
polyene cyclization. It's a long story; I've actually written it up because I
sent my version of it to Eschenmoser recently because Eschenmoser published a
long, beautiful paper about the history of [Leopold] Ruzicka and the isoprene
rule in Chimia. That paper is factually incorrect by
my biased recollection, or my biased input. So I wrote my version of this for
Eschenmoser. Actually, that was six months ago. I've seen Eschenmoser since; he
said, "I will answer it." But he hasn't, and the history of it is complicated.
It's very difficult to put in historical context. At the time that I became
convinced that triterpenes came from the cyclization of polyenes, the
stereochemistry of these compounds was not known, except with respect to the AB rings.
[END OF TAPE, SIDE 8]
STORK: The postulate was that they would turn out to be trans-anti-trans. That,
I'm amazed today that I would have the courage to do stupid things like this. I
gave three colloquia at Harvard based on nothing whatsoever experimentally. I
was in my late twenties, pretty young, which you had to be to do this. One of
them was the one in which I proposed the steroid construction, in which Woodward
shared his three students with me. But these talks were based on nothing
02:50:00experimental. One other one was on the structure of various morphine alkaloids,
which I still remember. My poor parents. By that time I had moved to Cambridge,
Massachusetts. They didn't care where they were, so they tended to follow where
I went. So they were in Cambridge, Massachusetts. In fact, they had bought a
two-story house. We lived in the upper story and they lived in the lower story,
which was two blocks from Harvard, on purpose.
At one particular colloquium I was going to talk about the structure of certain
morphine derivatives that I had figured out were just incorrect in the
literature. I thought it was a good subject for a talk. So I was going to give
my talk on this subject, but no work had been done by me on it whatsoever. My
parents wanted to hear me give a talk once. So they sneaked in the back, and no
one knew they were there. My poor parents! Fieser's in the front row, and so is
02:51:00Woodward. Bartlett was also there. I went through my stuff, saying it can't
possibly be this, so obviously it must be this and that and so on. Fieser got up
with the first question, and he's kind of snarling. He said, "I think this is
outrageous." [laughter] There is Fieser, "I think this is outrageous. You have
the nerve to stand up here and say this, and you haven't done any experimental
work." He had a point, you know. [laughter] "You haven't done any experimental
work at all. Lyndon Small is one of the great lights in this particular field,
and you have the nerve to say that his work is not correct." (I didn't know
that. He was at NIH and was the morphine alkaloid person. He was an old friend
of Fieser's, and I didn't know that either.) My poor parents in the back, they
really picked a good one. [laughter] That was pretty brutal. It was a place
02:52:00where MIT people were there, Büchi was there; all these people were there. It
was pretty brutal. Eventually, when it was shown that I was right, Fieser
apologized; reluctantly, but he apologized. But the point is, it was pretty
dramatic. But it was, in fact, based on nothing but theory.
The polyene cyclization was the same thing, but it was early enough that at the
end of my talk, Fieser didn't raise hell. At the end of my talk, Fieser came
over and said, "You know, I don't believe that steroids come from polyenes. I
believe they come from [what was known at the time as] the essential fatty
acids." Arachidonic acid was known to be essential to the maintenance of health
in rats, so it was needed for something. Prostaglandins were not known at the
02:53:00time; they had not been discovered. We now know that the reason they're
essential is because they make prostaglandins. But it was an open thing. It was
a long chain molecule and you could curl it around and get a steroid shape.
Fieser believed that arachidonic acid was a precursor to steroids, which he had
perfectly good right to believe.
Robinson believed carotene was closer, and was the precursor; if you attached it
in a large circle and made bonds in between, which has nothing to do with
reality, nevertheless it's a polyene. My suggestion was that the trans-decalin
systems just happen to be the necessary result of a concerted closure of a
triene, whereas a concerted closure of a diene of the same structure would give
a cis-decalin. That was a rigorously correct deduction, whether in reality the
closure was concerted or not. That's another thing. But if it was concerted, it
02:54:00had to be that way. Therefore the possibility was intriguing that the
triterpenes, which were a more obvious result of closing squalene, could come
from this kind of thing. Then, if that was true, they would turn out to be trans-anti-trans.
They turned out to be trans-anti-trans eventually. Squalene had a couple of
extra methyl groups in what would be the C-4 position in cholesterol.
Cholesterol has hydroxyl at 3, the next position is 4 in ring A, and the
triterpenes have 2-methyls, which are the same 2-methyls as squalene. So it's a
lot easier to think that squalene could conceivably give rise to the triterpene,
than to give rise to the sterols. Now we know sterols are made by giving these
methyls up after the four rings have cyclized. Of course, there was no such
thing known at the time. Nevertheless, my idea was that maybe the sterols come
from a polyene, which I thought might have a plain unsubstituted vinyl group at
02:55:00the end. Not squalene, just a polyene. Later on, it was shown by Konrad Bloch,
using radiocarbon labeling that squalene was in fact the precursor and that it's
actually incorporated in cholesterol. Woodward then suggested to Bloch (I was
already here at Columbia at the time) that it wouldn't be that surprising if you
coiled squalene the way that I coiled the polyenes in my Harvard seminar. I
always resented the fact that Woodward could perfectly well have afforded to
give a footnote that perhaps only I would notice. Footnotes are really the
easiest way not to make enemies. Not necessarily make friends, but not to make
enemies. But that was not done and it really was not very nice.
That was the origin of that work. Eventually we did some work with that, but we
02:56:00messed up the chemical work. We thought we succeeded in demonstrating that you
cannot do these things chemically in a laboratory, a conclusion that was false.
Eschenmoser agreed, published his view that it was impossible to achieve
concerted polyene cyclization in the lab. Bill Johnson takes delight in showing
that quote of Eschenmoser's when he gives a talk on the subject, because Bill
Johnson then proceeded to demonstrate that not only could it be done in the
laboratory, but it was fabulous in the laboratory. He was a nice enough person
(and undoubtedly friendship had something to do with it) that he called it, with
no prodding on my own, the Stork-Eschenmoser Hypothesis. He didn't have to do
that, but it's very nice that he did. But he is the one who deserves an
absolutely major, major share of the glory because he showed that concerted
polyene cyclization can be a very powerful tool. It was one of the really few
novel synthetic construction schemes that was achieved. There's no question that
neither Eschenmoser nor I, nor anyone else, would have given two cents for the
02:57:00possibility of making four rings at a crack with complete control. No way. So
it's a jewel.
There is one thing that's really very interesting. My claim to some originality
in the operation was really based on the Harvard colloquium, which was maybe in
1950; I'm not sure of the date. Now, it is demonstrable that I gave a colloquium
on that subject because Harvard keeps the colloquia abstracts bound in the
Harvard library. My abstract is there as well as those of other people. It's a
two-page mimeographed thing, and it just says that "the implication of this
conclusion will be discussed," the conclusion being that cationic concerted
cyclization of a properly constructed acyclic polyene must necessarily give a
02:58:00trans polycyclic system. That's in there. But that the triterpene might come
from squalene specifically, was not.
Now, Eschenmoser's claim is that the first mention that triterpenes might come
from the concerted cyclization of squalene in a trans arrangement was in a paper
of his and Ruzicka that was published at the same time as our paper of
1955. Now there are two things about this, although
maybe Eschenmoser's answer, if it ever comes, would throw some new light on the
subject, I don't know. It is a fact that the paper with Burgstahler that we
published in 1955 is the legal basis for our claim to have something to do with
the polyene cyclization hypothesis. The paper by Eschenmoser, Ruzicka, Arigoni
and I forget the other [Jeger] is also 1955. But their submission date is not
02:59:00only later than our submission date; it's later than our publication date. It's
a not trivial fact that that paper's submission date is later. It's neither here
nor there, but you cannot make a great claim that they were first.
But I could never prove anything rigorously for a long time. So what? What does
that mean? My coworker, Burgstahler's thesis was submitted in 1952. Maybe
there's something in Burgstahler's thesis? And by God, there is; I have his
thesis up there. There is a page that says, "Squalene is drawn in a chair,
chair, chair ready to undergo cyclization to a triterpene." So it is actually on
record, somewhere, in an official document, that that kind of thinking was
certainly current in our lab a couple of years before we published it. All of
this is a history, which is of interest only to the people who were involved in
03:00:00it. But nevertheless, it has been a sort of emotional thing.
BOHNING: You mentioned Lyndon Small. I happen to have a quote here from a letter
STORK: I don't think I ever met Lyndon Small.
BOHNING: This was a letter written in support of one of your award nominations.
STORK: From Lyndon Small? It's a small world. [laughter]
BOHNING: It's interesting, especially in view of what you just said a little
earlier, and I'm quoting, "He and I have differed in some points in
interpretation of data in the field of morphine alkaloids. His contributions to
the field of morphine chemistry, I feel, are eminently sound if sometimes
speculative, which have my full respect."
03:01:00STORK: Well, this would have to be his view. Do you know there's a series called
the Morphine Alkaloids? As it happens, I wrote the chapter on morphine
reactions. But the fact is that the structures that
he proposed were wrong. The structures that I deduced were right (at least most
of them). He is right in the sense that they were speculative. Well, they were
not that speculative. We used his data as the buttress of my suggestions. It's
not that different whether I get the data myself or I take his published data.
But of course, in his eyes it would be different, and I can appreciate that.
It's the same thing that Robinson had against Woodward, that Woodward used
Robinson's data to establish what the correct strychnine structure is, and
Robinson's feeling was that Woodward was stealing his stuff. Of course, that's
ridiculous; if you're on the outside, you say, "What the hell. This data belongs
to everybody." I can understand Lyndon Small, though. That's certainly a
perfectly plausible quote from him.
03:02:00BOHNING: I've come across a number of comments about that morphine review paper,
because it wasn't really a review in the true sense of the word.
STORK: No, it wasn't and I'm very pleased and very proud of that paper. That was
the first review; the supplement was not very good.
That was probably written in 1950. If one teaches anything about these
mechanistic arrows, this is a very nice, elegant example. I didn't invent
anything there, I was just using existing structure data.
The thing which is really worth doing is to look at Robinson, the inventor, in
the discussion of a reaction transformation which is a magnificent
transformation in morphine chemistry called phenyl-dihydrothebaine, which is a
reaction product of thebaine, a morphine alkaloid. Treatment with phenyl
Grignard, followed by water, gives the normal result of adding the elements of
03:03:00benzene. The structure of this substance has nothing to do with morphine; as
Robinson showed, it has a large ring, and one ring is knocked open. It's just
totally different. Robinson makes an effort to use his curved arrows to explain
this. It's absolutely incomprehensible. One should read that; it's absolutely
incomprehensible. And yet, the proper use of his curved arrows makes the
transformation paths transparent. It's beautiful. He got the answer immediately
by intuition; he did not have the discipline to rationalize the answer, which he
felt was correct. I mean, he found the structure, after all. Robinson found the
structure of this substance, and then, after the fact, tried to explain how he
did it. How he did it must have been by revelation, but his revelations were to
be taken seriously. Then he tried to fit them into a rational mold, but he
couldn't do it. But his finding the correct structure was brilliant.
BOHNING: I have another quote here from Louis Sarett about that paper.
STORK: It's interesting to hear this stuff. I always wondered about what other
03:04:00people say; this is kind of interesting. [laughter]
BOHNING: I'm quoting here, "He did not, as he might have, merely write a chapter
reviewing the data and the literature. Rather, as in the rest of his work, he
made this nominal review a piece of incisive research in its own right."
STORK: That's pretty good. I couldn't agree with him more. [laughter] But that's
pretty good. Sarett himself is a major and not sufficiently recognized early
contributor to the business of being conscious of stereochemistry and
stereochemical problems. If somebody were trying to decide which syntheses
really were historical markers in the beginning of stereocontrol in synthesis,
Sarett's would be one of those because his cortisone synthesis is absolutely one
03:05:00of the very first to deal with the problems successfully. In fact, the term
stereospecific, which he defined for his own benefit, to be sure, I believe was
first used in Sarett's paper. Or, maybe, he said stereoselective. It should have
been stereoselective; I'm not sure which term he used. He defined this as a
synthesis in which the ratio of the wanted to the unwanted isomers is at least
whatever number you pick, which was the smallest number which he had in his
synthesis; seven to one, I think. So he could call this synthesis stereoselective.
But the truth is, it was conscious planning. The crucial business is not whether
somebody mixes a and b and it turns out to produce menthol. Menthol has three
asymmetric centers, so, on eone level, that's a pretty good accomplishment. But
this is neither here nor there, unless it actually contributes to the evolution
of chemistry, which means that there has to be some rationale that can be
transferred to something else, in a predictive way, from that thing. Sarett's
03:06:00synthesis meets this requirement. It was one of the first times. There may have
been others. I mean, someone had synthesized camphor before that; a Finn by the
name of Gustav Komppa synthesized camphor. It's awesome, it's brilliant, it's
like climbing Mt. Everest. But climbing Mt. Everest does not necessarily
contribute to advancement of mountain climbing equipment; it might. It may or it
may not, but certainly it can be an extraordinary achievement in human terms.
Komppa's synthesis of camphor was an extraordinary achievement in human terms.
So was Rabe's dihydroquinine synthesis. But not in furthering chemistry. It was
just amazing. What makes these syntheses amazing is that, given the inadequate
means, they actually got there.
But Sarett's synthesis was a rationally designed synthesis, really very pretty
and very elegant. Sarett himself was a brilliant experimentalist. He had
03:07:00actually, all by himself, in papers with just his name on them, modified cholic
acid through forty-two steps to transform it to cortisone. Unbelievable; it's
ridiculous and sounds silly. But Merck used it in a commercial process until
recently; they may still be using it for all I know. Forty-two steps; they
managed to make them efficient eventually, adding a lot to it, which was mostly
done under [Max] Tishler. Sarett's synthesis was brilliant, and he did it all by
his own hands, after having gotten his Ph.D. from [Everett S.] Wallis at
Princeton, who was an early reaction mechanism kind of person. So he was
essentially totally self-taught, a really pretty impressive person. That
synthesis is very, very, very beautiful. By contrast, if you ask who synthesized
03:08:00steroids, probably people would say Woodward. There's no comparison. Sarett's
synthesis is an order of magnitude better than Woodward's. Woodward had four
asymmetric centers and managed to control two and screw up two. Sarett actually
controlled them all; not perfectly, but it's actually beautiful.
BOHNING: You also had several papers on the SN2' mechanism.
STORK: That was good and bad. It turned out to be sort of the wrong kind of
reaction to get involved with. It was intriguing at the time. It turned out to
be a) enormously more complicated than anyone knows; even today, no one
understands it, and b) not important. That's a combination that you cannot beat.
[laughter] It hasn't been as bad as the structure of the Grignard reagent, which
03:09:00has cost taxpayers millions of dollars and is now understood to be irrelevant.
It's irrelevant because it's a mobile equilibrium and what is it in the
transition state, which is really all one cares about, and it has nothing to do
with the position of the mobile equilibrium per se. It's interesting, but it's
not that interesting.
It was not that bad, but it was not a reaction that has been of any use
whatsoever. There are various reactions which one thinks of as SN2', but they're
mechanistically different. They give the same overall result, like
palladium-based chemistry and various other things, but a different operation
altogether. The operation which is legitimately called SN2' is of essentially no
importance, although they still debate whether it exists or doesn't exist.
It's a question of whether things come on this side or that side, and whether it
does or not clearly depends on the nature of the displacing group. It's
hellishly complicated. We did some work on it, and fifteen years later I went on
03:10:00this again, just to show that it was really much more complicated than anybody,
including ourselves, knew. It became a known piece of
work because there were not that many qualitative mechanistic things at that
time, and these are qualitative mechanistic things. We ran into this because of
this crazy business of some morphine reaction products; because of these
compounds of Small, we decided we should really do something about it. I had a
graduate student at Harvard by the name of Frank Clark, who eventually went to
and still is at Ciba-Geigy as a senior research person. We worked on the
03:11:00structure of the so-called halocodides, the halogen derivative of codeine, and
established the structures. These turned out to be SN2' reactions. But the total
structure of the molecule biases the results. So then we decided we ought to
find out what would take place in a non-biased situation. So we slipped into
this; we should never have messed with it. The result of our work was to add
darkness to an obscure situation. [laughter] That was all.
BOHNING: I have a quote here from Sol Winstein.
BOHNING: He says that it was a "brilliant contribution."
STORK: I wonder who conned him into writing that. [laughter]
BOHNING: What I was going to ask you about is that in one of those papers you
had some footnotes about Ingold.
STORK: Oh, yes. That's actually amusing; it didn't have anything to do with
03:12:00chemistry. Woodward had developed a particular style at that time, using Latin
phrases here and there to buffalo the assembled multitude. Obviously, I couldn't
use Latin phrases, but the purpose seemed obvious to me. So my thing was that I
would use some English words which people didn't know. The test of that was
whether or not Barton had to use a dictionary to figure it out. So that paper
has a footnote that the British school considered the SN2' reaction their appanage.
BOHNING: I got out my dictionary to look it up. [laughter]
STORK: That's right. I was fairly pleased with that. But I got over that after a
few more of these things.
BOHNING: Did you have any interactions with Ingold?
STORK: No. Never. I heard Ingold lecture a couple times.
03:13:00I guess Winstein would have kind words to say about it because he sort of made
the case that the relationship ought to come out syn. We had proof,
quote-unquote, that it was syn, so he was favorably impressed. We now know the
situation is more complex than that. It's sometimes syn, sometimes anti. Exactly
which factors lead to that conclusion, I am not clear. But it's just not really
BOHNING: Coming to the Columbia period, I have a couple things I wanted to ask
you. There's still an awful lot of chemistry, and I don't know exactly how you
want to cover that.
03:14:00STORK: You could say, "What is it that I consider to be the most interesting?"
[END OF TAPE, SIDE 9]
STORK: I guess if I think about what I've contributed to the field, it probably
would be the business of stereo and regio control. And within that, probably the
enamine alkylation. It turned out not to be great
with respect to forming carbon-carbon bonds with alkyl halides, because the
reaction rate is too slow, but it is great, and in fact you can't do it any
other way, with the Michael type of operation. These are difficult things, and
03:15:00obviously my view and that of someone else, say that of Robinson, if he were
alive, would be different. Robinson wrote the first volume of his memoirs
before, mercifully, the world was spared a second.
The most interesting part is that he tried to destroy Ingold's reputation by
claiming that Ingold stole his stuff.
But he says other things, which have some interest. Although he is at least
willing to say that I "pioneered" the enamine alkylation, he implies that he
actually did this before. This is baloney, because what he did before, he stole
from some gentleman by the name of [J. Norman] Collie, who did the first
alkylation of something with an enamine. But that was acetoacetic ester, and so
the relationship is as if you said, "Well, you know you can alkylate acetoacetic
03:16:00ester, therefore you can obviously alkylate butyraldehyde." Well, there's a
world of difference. You can't alkylate butyraldehyde. So what Collie had done
is to show that if you made the amino derivative corresponding to acetoacetic
ester, which actually exists in the enamine form because its vinylogous of an
amide when it's conjugated (it's the enol, really, NH2 "enol"), that thing will
alkylate like the related enolate on carbon. The fact is that you can use a more
pragmatic point, which is that before we published our work, no one could or
knew how to alkylate something like butyraldehyde, and in fact afterwards you
could. In my opinion, that was very important. The history of how we came to do
that, I wrote up for Science Citation Index.
03:17:00BOHNING: Oh, yes. Eugene Garfield and what he called "Citation Classics."
STORK: Yes. Citations Classics. That stuff is in there, so there's no need to
discuss it here. At first, it wasn't so great with alkyl halides so we developed
some thing which people have also forgotten where it came from, which is the
metalloenamine alkylation. It turns out that if you want to make
2-methylcyclohexanone or 2-methylbutyraldehyde, the enamine is poor to
worthless. What we did is to make an imine and deprotonate the imine; alkylation
of that, even when it comes from an aldehyde, is great. The reason being that
the double bonded-N-R is much less reactive than double bonded-O, so it gives
you time to form the imine anion. It doesn't self-condense.
03:18:00So the alkylation of the metal salt of an enamine with alky halides of all types
is something that we did, originally. I felt a great thrill at the time, because
we showed that even a Grignard reagent (we used ethyl Grignard at the time)
would deprotonate an R-CH2-C double-bond NR, the imine of an aldehyde, rather
than add to it. At that time everybody believed that the reaction of an imine
would be the same as that of a ketone. They would just add the Grignard reagent
to the C double-bond N, which indeed they do if the imine is that of an aromatic
aldehyde, because they can't do anything else. This is all people had been
studying because these are the ones that are easy to make. And so, when we
decided that maybe our reaction would actually work, and it actually did work,
it was a great thrill. Later on, I switched to lithium amide bases and also, for
03:19:00the first time, used dimethylhydrazones as special imines to do overall ketone alkylations.
Now, I'm sensitive about this because that is a reaction that everybody believes
Corey invented. Now, Corey did nothing wrong. Corey did nothing wrong
whatsoever. His first paper on this gives us credit, three years before, for the
alkylation of N, N dimethylhydrazones. But Corey and his collaborators, mostly
Dieter Enders in Germany, published masses of papers on this stuff. So it's now
become the Corey-Enders reaction, which is the sort of thing that's frustrating.
Corey's most quoted paper is not his most important one. Corey has many, many
important papers. Corey is an outstanding chemist, let's not misunderstand what
I'm saying. It's just simply that it is society that does this; Corey did
03:20:00nothing wrong in particular. Corey's most quoted paper is the
tertiary-butyldimethylsilyl protecting group, the TBDMS protecting group. One
paper that I love is a paper by Ian Fleming who is at Cambridge University,
where the first sentence says, "Stork introduced the tertiary-butyldimethylsilyl
protecting group into organic chemistry," which happens to be
correct. This work was with Paul Hudrlik, who is now
professor at Howard University in Washington. He has continued doing very
beautiful work in silicon chemistry. The first use we made of the TBDMS
protecting group was to protect enolates of ketones. Corey made contributions
and a very important one is the fluoride removal of the silicon group. That's
Corey, and that's non-trivial. We were removing it with dilute acid, but if you
do it with fluoride, it's universal. So he contributed to taking the silicon off.
03:21:00That sort of thing can get you annoyed after a while, because we don't really
like to publish masses of papers on a particular thing. That has to do with
marketing. I think marketing is important. But nevertheless, in a sense I want
my cake and eat it too. I don't want to pay the price of establishing myself in
a field. I know this wouldn't work. As I said before, if I want to sell a soft
drink that is as good as Coca-Cola, I have to be prepared to make an effort to
sell it. You can't just say, "Well, my cola is just as good." One has in the
back of one's mind that science is different, because people know how to judge
for themselves; but that's really not quite true anymore.
I thought that was an important thing because it succeeded in doing
monoalkylation of ketones and even sensitive things like aldehydes, with alkyl
halides. This was in addition to what one could do with enamines, with the
03:22:00acrylonitrile, ethyacrylate, acrolein type of species, Michael type of species,
among other things. So that was an important thing.
The other important contribution (and all of this has to do with the chemistry
of ketones, what I'm talking about now) was this business of the regiospecific
construction of enolate ions and their trapping as silyl enol
ethers. The idea is that you would produce an enolate
ion by a kinetic process designed to give that regiochemistry. You trap that
structure as a trimethylsilyl enol ether, or TBMDS enol ether, establish whether
it's correct or not by NMR, then you regenerate the lithium enolate from the
silyl ether. That's our contribution with Paul Hudrlik. That is, the silyl ether
with methyl lithium gives tetramethyl silane and a regiospecifically produced
03:23:00We were the first ones to show that lithium enolates could retain their
structure during alkylation, in contrast with sodium or potassium enolates. This
was done in the course of our work on the mechanism of the lithium-ammonia
reduction of ketones, which we showed gave a lithium enolate. We showed that the
thus produced enolates could be alkylated. This was
the first time that either of two possible lithium enolates could be made at
will and used in producing a new bond. That has been used a lot. We showcased
that process in the lupeol synthesis.
Some things actually gave us a great thrill, which are not particularly
important. Some were important, but not that much. For instance, the
prostaglandin synthesis from glucose is a beautiful piece of
work. It was not all that important, but in a way it
sort of was one of the landmarks of establishing that you can use the chiral
03:24:00sugar pool to make a complex chiral compound which is not obviously embedded
within the glucose structure. There were others like this. They were just simply
a thrill. Like solving a mathematical puzzle. You get a thrill, but it doesn't
mean that you're necessarily making an important mathematical contribution. But
that one was a thrill.
In the Aldrichimica article, I put in the structures, as you might possibly have
guessed. [laughter] I actually think every single one of them shows something
that was not known before. I think this is true. Some are more trivial than
03:25:00others, that is true. The lupeol synthesis, I think I mentioned before; it is a
very nice one. In this next one, there's no new chemistry. This is a Woodward
type of construction in the sense that the knowledge required to build this was
all available. It's a very pretty synthesis, but it's not anything new, except
that it highlights the importance of blah-blah-blah, which however is something
that one knows; in this case, that other things being equal, you tend to form a
new bond perpendicular to the enolate plane. [Actually, it also showcased the
reaction that deserves to be called the Stork-Danheiser synthesis.]
BOHNING: Which one is that?
STORK: But that was known, and if anybody would deserve credit for that concept,
it would probably be Corey, who was the first one to point out the importance of
stereoelectronic factors in organic synthesis. I think that's Corey's greatest
claim to fame, in my opinion. It's a very important one, in which he
demonstrated that directionally, an enolate ion is more accessible perpendicular
03:26:00to the plane (axial) than equatorial. I think if one were really tracing where
that comes from, it's Corey.
The yohimbine synthesis is a very nice application of the enamine
construction. Another very nice synthesis was the
erythronolide-A construction. That really is a tribute to the person who did it,
Scott D. Rychnovsky. He is now an assistant professor
at Minnesota, [now professor at U.C. Irvine] and just recently got a
Presidential Young Investigator Award. That was a great class that year. Dan
[Daniel E.] Kahne was another one; he got promoted and got tenure after just two
and half years at Princeton. Not bad. He also got a PYI. These are great people
to be associated with.
03:27:00This synthesis did establish a principle, which is an important one in
construction, which is that with all the advances which have been made, and
which are important in controlling the aldol condensation, they have not reached
the point (they might reach the point, but they have not reached the point yet),
where you can sit down and in all cases predict the outcome of a sequence. You
have a fair probability that it would be this, but you cannot be certain of it.
One would like to have a thing that you can plan ahead of time, and you know it
would give only this particular stereochemistry; this is what our construction
was designed to do. Essentially it's a step backward. That is, the advances in
the aldol condensation chemistry that were due to Masamune, Evans, Heathcock,
03:28:00are based on using metals to produce temporary rings through chelation. Because
rings have more shape than floppy arrays, one can use them to predict and
control stereochemistry much better than plain old acyclic chains.
But you can go one step further, which is one step backwards if you want.
Namely, if it were a real ring, it would be even more predictable and certain,
because in compounds, which have a lot of oxygens, chelation probably should
involve this oxygen, but might involve this other oxygen. So the ambiguity has
to do with the difficulty of deciding an order of precedence of which one is
more likely, or not more likely. It does seem simple enough that you could do
it, but as it gets more complicated, it's difficult. So this was, in a way, a
throwback to covalent bonds, showing that you could use a simple, five-membered
03:29:00lactone system to assemble any contiguous stereochemistry that you want of a
methyl and a hydroxyl, like the polypropionate unit which is found in things
like this erythronolide.
This other one is just an erythronolide sequence that we did earlier. We did not
complete this to the large ring itself. This is a different construction. But
it's the same sort of target as the complete erythro-molide A, which we did with
Rychnovsky. This one was done with Ian Paterson, who is now a Lecturer [now,
Reader] at the University of Cambridge in England and is doing very
well. So that was an important thing.
This next thing is actually very, very good. The regiospecific enolate and
03:30:00alkylate formation is the first one to form an enolate of known regiochemistry,
allowing to form a bond, even at the less likely position, more crowded
position, because of this deterministic control. That was very important. [It
was first used for regiospecific alkylation with alkyl halides.] Then we
enlarged it to the Michael addition, which was impossible before because in the
Michael, you start with anion and produce a new anion. If there's no proton
source there, you just get anionic polymerization. With an alkyl iodide it would
simply produce an iodide ion and that's the end. You don't produce a new anion.
The question was how to solve this, and we solved this by introducing the
-silylated vinyl ketones, which actually do that. They will trap ordinary
enolate, the reason for that being a trivial reason. You have to find something
that would produce major crowding so that after the addition the new anions
would be less reactive. Also, this something that makes it extremely crowded has
03:31:00to drop off when you work the reaction up, This happens to be true of silicon
next to carbonyl. This silicon assisted aprotic Robinson annolation was actually
one of the more useful silicon chemistry reactions we produced.
Another one, is the ring formation by the bimolecular reduction of a
keto-olefin. It has led to a lot of further related work by many people. This we
did by electron addition to keto alkyne with lithium and ammonia to produce
initially a radical ion. Shono has shown much more recently that one can, not
surprisingly, do the same thing electrochemically. Molander has shown that one
can use samarium iodide as an electron source, to do the electron addition. Our
reaction amounts to an acyloin condensation, but it was the first not to be
between two carbonyl groups. You use a carbonyl and a different group [a
carbon-carbon multiple bond], producing new bonds for various kinds of systems.
03:32:00That was a very important thing, which was done with S. Malhotra for his Ph.D.,
together with Dr. Uchibayashi, a Japanese postdoc.
There are many others, which I think have some importance. Our involvement with
usnic acid is historically amusing, although it is a trivial point, a little
footnote of history. This is a natural product, which was of interest to people
because it was claimed to have antitubercular and antibiotic properties. It has
a quaternary center, here, and it's optically active. When you heat it up it
racemizes. Now, in the days that this work was done, Woodward and I thought,
just in conversation, that this can't possibly be the structure because it does
not have an enolizable center, or anything of the sort. Now if one showed this
03:33:00to any graduate student, he would immediately know the answer because, by now,
sigmatropic rearrangements are common knowledge. This turns out to be one of the
first. What happened is that this chiral cyclohexadiene isomerizes to an acyclic
and achiral triene, reversibly. It's what is now called a sigmatropic
rearrangement. This was long before those rearrangements were codified. It's
amusing that we both worked on this and couldn't figure it out; there seemed no
way this structure could be right. Then one day I thought of what the answer
was, and I called up Woodward. I was sitting in that little closet of an office
in Chandler where we have two refrigerators now. I called up Woodward and said,
"I know what it is." He said, "What is it?" I told him. There was a silence and
he said, "It's pretty simple, after all." [laughter] But it's amusing that
eventually, it turned out to be a sigmatropic rearrangement, and the genius that
03:34:00he was, gave a major significance [and a name] to the Woodward-Hoffman rules.
More recently, there are two things that I care about, which are not illustrated
in the Aldrichimica article. One is our free radical cyclization work. That had
a psychological impact, because although there was very intelligent work before,
it was done by physical organic chemists. Organic chemists had a vague suspicion
of them because the physical organic chemists were trafficking with the enemy,
the physical chemists. Many physical organic chemists thought the organic
chemists are intuitive clowns. Because there's absolutely no question that the
bases of what one does in organic synthesis with radicals were laid by people
like [Cheves] Walling and [Athelstan] Beckwith and Ingold's son, [Keith] Ingold.
There is actually a nice quote. I talked with Ingold's son, and he said his
father had absolutely no use for free radicals. One of the reasons Keith left
03:35:00England for the National Research Council of Canada, is because of what his
father said. I've forgotten the exact quote now, but essentially it was, "Free
radicals are just not tolerated in this laboratory. [laughter] If you want to do
it, go somewhere else." [laughter] He went to Canada.
This was important work. The important thing we contributed is not so much the
radical cyclization work, it is the demonstration that the shape that you
produce by the free radical cyclization act can be taken further advantage of,
03:36:00if you're making a six-five or a five-five system. In six-five bicyclic systems,
if you construct the system so that you close the five-membered ring onto a
cyclohexane ring, the properties of the mechanistic situation are such that you
must get a cis-fused ring, and if you get a cis-fused bicyclic ring it will have
a convex shape. And if it has that shape then it's only further accessible from
that convex side. Therefore, the act of radical cyclization would control the
stereochemistry of what happens next if you could trap the radical resulting
Now, that was thought to be pretty near impossible because the time scale of
radical reactions can be compatible with intramolecular, more easily than but
not necessarily with intermolecular, especially in the presence of a hydrogen
donor. The time scale for something to happen to a radical is around ten to the
fifth per mole per second, rather than ten to the minus five, which is found for
some ionic reactions. We nevertheless succeeded in trapping the newly formed
cyclic radical with tertiary-butyl isocyanide, to transfer a cyano group with
resulting predictable stereochemistry, and that cyano group can then do
03:37:00functional chemistry. That was an important result that led to many other things
that many people could do with this process. We made prostaglandins with it. But
what molecule we made with it is not as important as the general result that
once could make a particular shape; and that there were species that could in
fact trap to get something useful and of predictable stereochemistry as a
corollary of that shape.
Another important recent achievement is something on which our first paper has
just been accepted. We've done all the work; the
first one I got myself to write is coming out in a month or two. I've just
finished reading the proofs. It has to do with the fact that an awful lot of
reactions which would take place, including radical cyclization, if only they
were intramolecular, are borderline enough that they don't quite make it when
they're intermolecular. The intramolecular advantage is a factor of maybe fifty,
03:38:00some number like that. That is, you gain fifty times the intermolecular rate;
you don't gain ten thousand times, you gain fifty. But that fifty can sometimes
be just the difference.
One such case is that you have a radical somewhere, and an acetylene somewhere.
The rate of addition of the radical to the acetylene is too low to do anything
useful involving trapping. It just won't make it. Let's say its butyne, a
simple, non-special alkyne. On the other hand, one knows that cyclization into a
triple bond can take place. So that's one of those cases, where if only you
could make the intermolecular reaction behave as if it were intramolecular, then
it probably would work.
Obviously, what you want to do is to have a temporary connection, which falls
off after the reaction. So you connect a and b, they now react in an
intramolecular mode, and the connector then falls off. It is as if you never had
it. So ideally, the connector has to fall off in the process that you use to
03:39:00work up the product. This turned out to involve silicon again. So you attach the
two reactants to a silicon atom. We've done this with photochemistry, with
Diels-Alder reactions, and with C-glycoside formation, which is the subject of
the paper that we have in press. It concerns the
formation of c-glycosides of known stereochemistry at the anomeric centers,
which now bears a carbon rather than an oxygen. There are all sorts of methods
of making anomeric c-glycosides, but this one is totally predictable
stereochemically. If this reaction gives a product, it has this structure,
that's all. That is very interesting. But insofar as methodology is concerned,
the temporary silicon connection is probably the most important thing we've done
03:40:00in some time. That's something that's important.
It also allows you to reverse normal regiochemistry. If you have a Diels-Alder
reaction, which normally goes this regiochemistry and you now tether the two
pieces it now can only get together this way, because the tethering constrains
it to do that. So we can add ethyl methacrylate to a diene. Normally the
carboxyl ends up next to this substituent, but you can make it produce the
reverse regiochemistry, just by attaching and then, dropping off, a silicon tether.
BOHNING: One of the things I'm struck by, and I'd like you to comment on whether
I'm right or wrong, is that it seems to me that Woodward's synthetic targets
were picked in a much different fashion than the way that you picked yours. You
had a methodology, which you then used to explore your targets, whereas Woodward
seemed to have to go one up each time in
03:41:00complexity. Did he pick the target before he worried about the methodology? Let
me ask the question that way.
STORK: One important element in Woodward's targets, given Woodward's
personality, not surprisingly, was drama. That is, Woodward would not be likely
to synthesize a triterpene, because although it might be complex, it's not New
York Times material. So one of the criteria, spoken or otherwise, was New York
Times suitability. This was spectacularly successful. That is, the connection
03:42:00between Harvard and The New York Times was, and often still is, an impressive one.
[END OF TAPE, SIDE 10]
STORK: Nobody has synthesized tetracycline, as of this day. A Pfizer group with
Woodward synthesized a compound that has the tetracycline four rings. But one of
the major pains in the neck of the structure of tetracycline, a tertiary methyl
carbinol in ring C, is not present in the simpler compound they synthesized.
It's a perfectly interesting compound, but that sensitive feature is not there.
03:43:00It's not a natural product, although it has been claimed that you can grow some
cultures in which this simpler tetracycline analog will appear; that's possible.
It's not obvious. In any case, that synthesis made an editorial in The New York
Times. Not just a mention, it was an editorial, on the editorial page about "one
of the great triumphs of the human mind." Another case in which they were even
more absurdly enthusiastic, and which did not involve Woodward, was when the
Chinese synthesized insulin, which The New York Times claimed was also "one of
the most monumental feats in the history of chemistry." This is just absolute
hogwash; it's just ridiculous. It is equivalent to saying that a man spending
five days on a flagpole without food is a real triumph of the progress of
culture, or something. It's ridiculous!
03:44:00So one of the criteria is that it had to be glamorous. That's not unreasonable.
There's nothing wrong with that, particularly if other people haven't done it.
So long as you find enough of these targets, why not? It's perfectly reasonable.
In retrospect, if one analyzes what was motivating Woodward, unbeknownst to him,
it could be this or something else.
I was asked to write, and did write, a small two-page obituary of Woodward.
BOHNING: That's the one that was in Science?
STORK: Right. In that I quote something that is actually true; you have to
understand the person's character to some extent. It was about his wearing red
03:45:00suspenders. His answer at the time, which was when he was still struggling as an
assistant professor, to the question was, "That's what the public expects of
their heroes." So that was a picture that he had; that was perfectly clear. His
other statement came when someone, half jokingly, said that something he did was
slightly crooked. He took great offense to that. Not to the word "crooked;" that
was okay. It was the word "slightly" that was intolerable. His response was, "If
I'm going to be a crook, I want to be the biggest crook there ever was."
[laughter] So there was that aspect which was certainly very important and
obviously motivated him to do great things; it's not necessarily wrong. So I
03:46:00don't know what motivated it, except that one thing was that he anticipated glamour.
My selection of targets is not clear-cut. My involvement in taxol is clearly a
slip. (I shouldn't really be doing this, but I can do it, it's okay. It's
interesting.) So there's an element of that. Of course, this has been encouraged
by NIH. You could not today get any money to make lupeol. You could "steal"
money to make lupeol; you could get a grant from NIH to make C-glycoside and use
it for lupeol. You can get away with it for a while, but not for all that long.
So NIH also had a hand in the process, if you want. They support work, and I'm
trying to synthesize some biologically active thing, more a thing that just has
an interesting structure. NSF will support work, but NSF has practically no
03:47:00money. I mean, it has a large amount of money, but the money that's available
from NSF, as I'm sure you know, is on the average enough to support two or three
graduate students. Period. So, majorly it comes from NIH, and if it comes from
NIH, so long as there are structures that have some sort of a shape, you'll do well.
So I'm not sure how Woodward selected targets. Well, part of the structural
thing, he was involved in earlier; his Ph.D. thesis was involved in a minor way
with steroids. What he factually accomplished was to brominate estradiol. Not
one of the largest accomplishments in the world, but, on the other hand, it was
early. He also did a very pretty thing, which was the so-called abnormal
Reimer-Tiemann reaction. It's not useful, but it is a very cute way of sticking
03:48:00a methyl group between two rings. Pretty good. So he had some emotional
involvement with steroids. There was strychnine, which had been one of his great
structure solving successes, so that was understandable that he would try to
synthesize it. And there's something that he did work on with Wasserman,
relative to penicillin. This never got to anything, but that would have been a
reasonable target. Eventually, he got back into this through the connection with
Ciba with cephalosporin.
So B12. There are things that I consider classic. The Mona Lisa, for example. To
my taste it is difficult to dissect ninety percent of its history from the Mona
03:49:00Lisa. I'm not sure if you succeed in doing it, it would basically be as great a
painting as everybody thinks it is. I am not sure that I would want anything to
do with a woman who looked anything like Mona Lisa. There's just a lot of
cultural overlay there. B12 is for chemists that sort of thing as well. A lot is
to be learned from what Eschenmoser did with B12 or what he was forced into
doing because of B12. Not a hell of a lot from what Woodward did with B12. Now,
Woodward claimed that's how he got into what is known as the Woodward-Hoffman
rules. That could be true; I have no way of saying that's true or not. Of
course, that could be an argument for drinking straight bourbon because you
might not get a great idea otherwise. I don't know how compelling that is. But
with Woodward, it could have happened to him with any other target; it just
03:50:00happened with that one. I don't know.
But if you look back at a piece of work and you say, what is it that you know
now? There are several aspects, one, which could legitimately be what is it that
you now know that was not known before? That's a tough one. For example, making
polyethylene is not synthetically complicated stuff, it's not mechanistically
complicated. It's not the multi-step, Mount Everest kind of stuff. But nobody
could deny that it's enormously important. So something could be not terribly
glamorous, but extremely important, or vice versa. I think that B12 was vice
versa. It's enormously complicated.
There's a worse example. A recent example would be [Yoshito] Kishi's
03:51:00construction of palytoxin, which The New York Times, with its usual perspicacity
called the Mount Everest of organic chemistry, or maybe it was Kishi who called
it that, I don't know. It's nonsense. It's a common nonsense in current organic
synthesis. The reason why the public, and by public I mean chemically-aware
public, thinks that synthesis does not have much future is an argument that goes
something like this. It is clear that you can now make things like B12, so you
can make whatever you want to make. This impression is reinforced because the
Kishi palytoxin thing has I don't know how many asymmetric centers in it. If you
tell me that it's one hundred, it's quite possible. It's some really phenomenal
number; maybe fifty. It's some huge number. And people can put that together,
03:52:00asymmetry and all. Fantastic. B12 does not have that many asymmetric centers,
maybe four or five, but generally it takes forever to write it and most people
can't do it, so it must be very complicated. Besides, it took forever and masses
of people, so it must be complicated. But the fact is that the state of the art
is nothing like what people believe, and that's easily demonstrated. That state
of the art has reached perfection in only one area. It is perfection in the
field of oligodeoxynucleotide synthesis. That is absolute perfection. You can
make a molecule with forty asymmetric centers in three hours, all while you
sleep, by linking together ten pieces; each one has four asymmetric centers. You
produce a molecule automatically in a predictable number of hours with a
03:53:00predictable purity. It's incredible. So that is perfection.
Contrast this with something like taxol, which is a perfectly good example.
People have been working on its synthesis now for several years, and serious
work has been going on this target. When it will be done, it will be something
like thirty-five steps. Assuming somebody works with reasonable seriousness you
should be able to do one reaction a day, so it should take thirty-five days, so
about seven weeks, if you work on Saturday and Sunday. But we know, you know and
I know, that it's likely to take something like years. The difference is the
state of the art because these are not stupid people who concoct these constructions.
Furthermore, there's another thing that gives a hint that there's something
funny there. By now, there must be at least forty groups worldwide, probably
03:54:00more, working on taxol. In the greater New York area there are at least six.
They're all different. They're all different syntheses, which sounds nuts but
you don't get a huge waste of money because everybody's trying to do the same
damn thing. This would be a problem if you were doing mechanistic work or
structural work. If people work on a structure they must all end up with the
same structure if they are right. If people work on a mechanism, mechanistic
work, they must end up with the same mechanism, if they are right. But in
synthesis, they can all end up with something different; it's like writing a
novel or something like that. But that also suggests that the state of the art
is not that advanced when all these people, who are very competent, all try to
do the best they can and they all come out with different answers! [laughter] So
that is the state of the art. It's nowhere near the sort of perfection which you
know is possible, as with (and admittedly much simpler because it's repetitive)
oligonucleotides. But even with polypeptides, we can't quite do that. That is
less repetitive than the nucleotide business. Even if polypeptide synthesis is
03:55:00not that automatic, it's getting close.
Another problem is the following. People say, "Oh, there are sixty asymmetric
centers in palytoxin," which is a red tide poison for fish. But these people are
all cheating. How do they synthesize a sixty asymmetric center compound? They
link together, let's say, ten pieces with six asymmetric centers each. Anybody
who makes a polysaccharide or a polynucleotide or insulin, for that matter, does
that. Insulin has a hundred asymmetric centers, and somebody has made it that
way. "Oh, that doesn't count!" But that's exactly the way they make these one
hundred asymmetric centers. They don't solve any hundred asymmetric center
problems. If that could be done, they would be right. Chemical synthesis would
have reached perfection. But they only solve a six asymmetric center problem
over and over and over again, and then link them all together like sausages.
That's a very different thing. That's not the same thing at all. So the state of
03:56:00the art is not nearly what people perceive. Essentially the public, and by the
public I mean the educated press and the chemists who are not doing synthesis,
don't really understand what's involved in this kind of synthesis, because it's
not easily comprehensible, and so much showmanship is involved anyway.
Part of the Woodward mystique was due to the fact that he could give a lecture
that was absolutely fantastic. He would just start at one end of the blackboard,
and the structures were good enough to be photographed and used directly. You
didn't need Chemdraw; just use his structures. And they were drawn in color,
too. But he would do things like drawing the first seven steps upside down.
Nobody knew they were upside down. You'd see it there, and you were killing
03:57:00yourself trying to find out what the hell was going on, and then magically he
changed the drawing by turning it around--ah! This is great; as a theatrical
experience, it was fantastic. Educationally it was not that great, because
people had no clue what the hell he did and could never reproduce it in a
million years. But it was impressive.
In that sort of thing, the magic is that the audience is simply told that A goes
to B, which goes to C, etc. The lecturer spent seven years trying to make this
molecule; he gives a fifty minute lecture. The picture that is conveyed is that
he knows what he's doing, A goes to B goes to C. Obviously nobody wants to take
two hours to tell you about each step. Who cares? It's a little bit like
03:58:00somebody who climbed Everest; do you really want to know everything? So, the
picture the audience gets is of a much more rational and controlled process than
it really is.
A lot of people are doing very good synthesis in this country and in Japan in
particular. It's less today in England because they are in such bad financial
shape; it's not their fault. The truth is the British are still doing extremely
well, considering the circumstances. The Japanese are doing great,
unfortunately. I should not say unfortunately, but, well, they're doing great.
And we are doing quite well. There's a lot of very good synthetic work. There
03:59:00are people like Danishefsky, [Paul A.] Wender, [Larry] Overman, [Clayton]
Heathcock, but not that many others. It's not that many. [Incidentally, all four
were postdocs at Columbia.]
There are lots of very competent people who do great things. Some of it is
moving the field forward; there's no question about that. The total number of
people who do intelligent and important things is higher than it's ever been.
There aren't that many people who could put together a strychnine synthesis.
Strychnine has only once been synthesized by Woodward; nobody else has done it,
[since this was taped, it has been accomplished several times] which is really
impressive. To my taste Woodward's strychnine and reserpine syntheses are an
order of magnitude more important than B12. That is not necessarily what the
04:00:00I'm sure that was more than you cared to hear. [laughter]
BOHNING: No, absolutely not. I just wanted to ask you a few more things about
Columbia. You've been here for some time. Did you ever have offers to move elsewhere?
STORK: Well, I think we mentioned Pauling. Incidentally, Pauling visited me in
that little closet that was my office. That was impressive. That little closet
also had Pauling in it. Some of the molecules in there are exhaled by Pauling
and are stuck on the wall. [laughter] Yes, Pauling came in to talk me into going
to Caltech. He actually came, personally. This story is one I couldn't resist
telling. I told that story and I think it's in there.
BOHNING: Yes. It is.
STORK: About how he came to lunch.
04:01:00BOHNING: You said you liked the large city.
STORK: Yes. I went through all sorts of rigmarole with the Caltech thing. I told
Hammett I had this offer. It was not a question of playing games at all; today
people would think I was crazy. I told Hammett that I would just think about it,
and that I would certainly let him know when I decided one way or the other.
He'd be the first to know; it was not a question of playing games. I went
through making various lists; plus this and minus this.
There's actually a very useful way to tell what a person's subconscious feels.
You get them to make lists, or maybe you flip a coin. I've used this with
friends of mine, trying to decide should I take this job or that job: you can
just flip a coin. You can tell from their reaction what their gut feelings are,
which they're not necessarily aware of. If it comes out in favor of doing this
or that thing, they say, "Well, I don't know about that." [laughter] So any time
04:02:00my lists came out in favor of going to Caltech, I adjusted the parameters, so
after a while I decided I just didn't want to go out there. [laughter]
I could be happy anywhere; the truth is I was quite happy in Madison even
though, when it was minus twenty degrees Fahrenheit, you get the acute
experience of having your scalp shiver--a strange thing--if you don't wear the
proper clothing. [laughter] But you get used to it. I must say, if you have to
be stuck inland, Madison is one of the nicest places. Have you been there?
BOHNING: No, I've never been to Madison.
STORK: It is a nice city. It has a nice lake called Lake Mendota. There's a
cafeteria where you take your tray on the terrace overlooking the lake with
boats. Pretty good. Nice woods. I liked it there fine. Most chemists spend so
much of their time in the lab environment that they care about the quality of
the students, and their lab, and plausible colleagues, and bothersome colleagues
04:03:00(only minimally). They could be almost anywhere.
I have to prove this. I've convinced myself that I like an urban environment
much more, but I'm not sure that this has really been tested. It's been the
environment I've been in, whether I was in Paris, or even Nice. Nice is an urban
environment; it's over a million people. Where else was I? Madison was not a
large city, but then I was in the lab. Boston and Cambridge were an urban
environment. This is an urban environment. I have a feeling I would go nuts, if
I was not in a large city. But that's probably not true, because I would be in
the lab, and I would be quite happy. [laughter] My kids would probably like it
better not in a large city, so it's not so obvious.
04:04:00What it may represent is a considerable amount of inertia. If you are at ease
with this particular chair, you don't necessarily give it up for this modern
BOHNING: Frances Hoffman also credits you with building up the organic group
here at Columbia from obscurity in 1952.
STORK: That's her word, which she gathered I guess from other people. Well,
obscurity is not fair, because the fact is that the major person associated with
organic chemistry here was a gentleman by the name of Marston Taylor Bogert, M.
T. Bogert, Col. Bogert. I guess he was a colonel in the chemical warfare service
or something like that. No, maybe it was not colonel, but it must have been
04:05:00something of that type. It's very difficult to look at things and decide if they
were important or not, because now they no longer are. If I look at Emil
Fischer's work, I say that's kind of a silly way to make glucose. But if I put
it in context, it's awesome, it's awe-inspiring, it's extraordinary. Bogert was
one of the pioneers in terpene-related synthesis at that time. You say, well,
that's pretty trivial, but at that time he was a pioneer. Bogert was before
Fieser. I really don't know what the dates are, but he might have been
contemporary with Roger Adams and people like that.
BOHNING: Oh, yes. Probably even a little earlier than that, I would say.
STORK: Probably even earlier than that. But if earlier than that, there would
really not be all that much stimulation. So it's pretty impressive. Bogert was
04:06:00here long before my time. I don't know when he was here. There was a time when
Columbia was really not obscure. Elderfield, whose name was mentioned before,
was, in fact, a major figure in American chemistry. That's correct. Curtin was
mentioned before in another context and is a person who has not published very
much. He is at Illinois, as you probably know. He has not published very much,
but what he does is extremely intelligent and sophisticated. He studies
reactions in solid crystals, and such; he is really a pretty sophisticated person.
So, by the time I came here, there were great people. Physical was always pretty
good. [Harold C.] Urey was here at one time, and so was [George] Kimble. So
04:07:00there were really outstanding people. LaMer was well-known. And at the same time
here there was Doering, Elderfield and Curtin, all of whom were outstanding
people. At that time Curtin was one of the very definitely recognizable names.
Any one of them could not stand the other two. So they all simultaneously
decided, "I've had enough of this. I'm leaving." As it happened they all left,
because they all came to that conclusion. And so the place emptied. Doering went
to Yale. Elderfield went to Michigan. I remember he became interested in growing
04:08:00various kinds of roses in Michigan. It was either Michigan or Michigan State; it
was one of those places [Michigan]. So he went from here to there. And Curtin
went to Illinois, and that was that.
The only person who was left here, believe it or not, was a former student of
mine, one of my first students, Harry Conroy. In many ways it's a sad story,
that of Harry Conroy. He was one of the early geniuses of structural chemistry.
I mean early in his lifetime, not early in the history of chemistry. He actually
did something that was certainly easily as good as anything Woodward ever did in
structural chemistry, which was to deduce, just from reported chemical
04:09:00transformations, the structure of picrotoxin. He later added NMR data. He was an
early practitioner of NMR in complex structure analysis. The picrotoxin paper of
Conroy is a classic. There's only one name on that paper; Conroy did the entire
work in an independent year as a postdoctoral fellow at Harvard. It was just
absolutely a brilliant piece of work. He came here as an instructor.
The entire department consisted of Conroy in organic chemistry, one instructor
and another person by the name of Layton McCoy, who eventually went to the
University of Missouri. Layton McCoy was a good organic chemist, but also
non-tenured. So there were two non-tenured people representing the entire
organic or non-physical area because there was probably no inorganic chemistry
at the time. There was food chemistry, which was the closest thing here to
04:10:00biochemistry. There was a gentleman named [Charles Glen] King, who claimed to
have had a major part in discovering vitamin C. That's not totally
inconceivable; that could be true. He did some feeding of rats, or something
like that. But that's all. So the fact that there was friction and that it was
an impossible situation is certainly clear. There was nobody to act as a
spokesman for the organic group.
Conroy decided he had enough of that and left in midterm. He essentially told
people to go to hell. He was a young man and he was all alone here. He expected
major approval from Woodward and Doering, who by that time had left here and was
04:11:00at Yale. Woodward and Doering were very good friends and their verbal attitude
towards the world was essentially the men on a horse picture. If you don't like
it, tell them to go to hell. So Conroy, having actually performed according to
this message, expected, minimally, to be patted on the back. What they told him
was what I had told Conroy before, "You are crazy." The minimum that I had tried
to explain to Conroy was, "When you quit a job you should have another job lined
up; then you can be as outrageous as you want. But it's bad to do it in reverse
order." [laughter] Poor Conroy. It took him a half a year to get a job after he
got out of here. And it was only because Max Tishler at Merck was extremely
impressed with Conroy, whom he had met at Harvard. Tishler created a position at
Merck to let Conroy do whatever he wanted for a year. Remarkable. Then Conroy
went from there to Yale.
04:12:00That only left Layton McCoy at that time. Otherwise, I would probably be selling
soap somewhere. But the fact is that Roberts was pushing my coming here. I think
this happened because they offered a position to Jack Roberts in this
department. He was not willing to come, but he suggested that they needed to get
me here, which was nice. And it also was nice because they actually needed
someone. Oh, there was Charlie Dawson. Dawson had become interested in
biochemically related things, such as purifying the proteins that are involved
in poison ivy transmission. So even though he taught elementary organic, he was
not really involved in research in organic chemistry, except in a very
[END OF TAPE, SIDE 11]
STORK: He was making various phenols to see where they complex with proteins to
04:13:00make antibodies that were related to poison ivy.
The department was not obscure when I arrived; then it just exploded. As I
described the laboratories to you, this was not a place that was even
conceivable at that time for an organic chemist. Even now, after we spent an
outrageous amount of money, it's barely plausible, in present modern times. Any
time that we bring somebody in here it costs a million dollars to set up a place
that is operational, which is not unlike what it costs anywhere else, but it
does cost that here. So it was rejuvenated.
Now, you can say that I built the department; one of the major things I did was
to bring Breslow in. After that we both decided that we should add Tom [Thomas
04:14:00J.] Katz. Tom Katz has not published all that much, especially in recent times;
he's having some trouble adjusting (and so have I, so has Nakanishi, and so has
Breslow) to the difficult, let's put it that way, to the difficult science
support climate at the moment. It's difficult. But Katz is an extremely valuable
member of the department. He's very smart and he is a very good lecturer. He is
perennially young and interactive with the people whatever age they may be. We
brought him from Harvard, where he actually got his Ph.D. with Woodward. He did
not postdoc, but came here directly.
[Nicholas J.] Turro came through the Jack Roberts connection. I was involved in
bringing him here, but only as a conduit, not as an initiator. It was Jack
04:15:00Roberts who was visiting at Chicago and said it would not cost us much to bring
him from Chicago to New York; it was well known that we were cheap. So we could
afford to bring him over here, which we did. I was sold on Turro. I have no idea
what he is talking about in his photochemistry. The truth is I don't know that
much about it, except in general terms. How or where it fits in the development
of photochemistry I would have no way to tell. But the main reason why I was
suggesting bringing Turro here was that he told a joke that was so bad, so
outrageous, and so long that I decided he must have enormous self-confidence, he
clearly has enormous drive, and is clearly intelligent, so obviously he would be
perfectly okay. But it's an exaggeration to say that I was involved in building
the department. The initial thing was really convincing Breslow to come here.
That's essentially it.
04:16:00Oh, there is Clark Still. Clark Still got his Ph.D. at Emory with one of my
early Columbia graduate students, David Goldsmith. So he got his Ph.D. with one
of my graduate students and then became a postdoc in my group. I made what he
would describe as an outrageous mistake. (He is a very kind person, so he might
not say this.) The outrageous mistake was to exile him to Vanderbilt, which I
think is what made his career. It forced him to work on his own. His ideas and
his skill were so much better than anything they could get, that it immediately
04:17:00became obvious that he was doing great stuff, and we brought him back here. So
that was pretty good.
Then there is the Paul Wender case. He got his Ph.D. with Fred Ziegler, who was
one of my graduate students here, and then was in my research group. In fact, he
got his job at Harvard as an accident. Woodward called me up to ask about person
X, whom I will not mention, who was in my group at the time, because they
thought that maybe they should consider him seriously for a junior appointment
at Harvard. X is actually very good and has made a nice career, and he's doing
fine. But I really didn't think there was a chance that he could make it, and
what I said is, "Well, that's perfectly possible, but you have to look at Paul
04:18:00Wender." He said, "I've never heard of Paul Wender, but okay." So they did, and
they did offer him a job. As they say, the rest is history. He's done very well,
and obviously became a very fine person. I remember that Paul Wender had an
offer at the same time from Indiana. We spent a lot of time discussing it. "Do
you want to go to the safety of Indiana, where it's unimaginable that you would
not get tenure, or do you want to go to Harvard, where it's essentially
unthinkable that they would give you tenure. But the experience may be worth
it." So eventually he had the courage and guts to go to Harvard and said, "Okay,
let's do that and I'll do the best I can." That worked out pretty well.
Now, we have slipped here. I didn't realize this until recently. One of the bad
by-products of having a sort of family department is that we did not realize
04:19:00that we are growing old. All of a sudden Turro, who I permanently think is
thirty-two, turns out to be fifty. And Breslow is having a party at an ACS
meeting to celebrate his sixtieth birthday. Now, he doesn't look sixty, even if
you know that he's sixty; he looks and he behaves as though he was forty-five.
But the fact is that he is sixty and Turro is fifty, and we've let that happen.
Probably it was not our fault. Until we got this outrageously expensive modest
addition to our space, the structural situation at Columbia was just that we had
no place to put anybody. It was the combination of possibly poor planning and
financial difficulties, the fact that New York costs twice as much to do
04:20:00anything as anywhere else, whatever it is. That together with the fact that we
didn't realize in a conscious way that we're getting older and that something
should be done about it, turned out to be a serious problem.
So we wasted a lot of time. We wasted more time because we decided to build a
new building and did three years of work with architects to produce this
building, which was supposed to be on top of the gymnasium. Three-dimensional
models of the building were constructed and discussions were held about whether
there should be a sofa against this wall or against that wall and were they in
the student room or was it the entire sofa group, which I liked. [laughter]
After that a member of the administration finally said, "Incidentally, how much
is this going to cost?" There were two architects, and one shuttled back and
forth from London, where he was, across the Atlantic, at the university's
04:21:00expense. He was a very good architect. His three-dimensional model looked nice.
At that point, the whole thing was killed, because the answer was thirty-two
million dollars. The university said, "Well, we were thinking more like eighteen
million dollars." I don't know if you've ever been involved in construction, but
once you have some plan, you can remove anything you want from it and it will
not decrease the cost. It just simply doesn't do it. So you have to start from
scratch. So that cost us another three years. Three years doesn't sound like
much, but it's a lot.
Then we made another appointment to the department. There's a young man who's
very good. In fact, he is probably going to be heard by the operation much
beyond anything that is reasonable. That is Bob Kennedy, Robert Kennedy. He's a
very intelligent guy and he has good ideas. When there's a colloquium here, he
04:22:00always asks not just a question to show off, but it's an intelligent, to the
point question. He knows what he's doing, and he's not going to make it. Why
not? Because a by-product of the operation is that there is a certain
personality to the department, and we are responsible for this.
The Columbia personality has been unkindly described as a group of people whose
natural tendencies would be to grab the microphone while someone else is still
using it. That's an unkind statement, which is not any kinder because I made it,
originally. [laughter] But it has some truth to it. This may be the description
of anyone who is going to make it in this world of chemistry; it's not that
04:23:00different. But it is damaging. This is one difference with the European system.
Overall it may well be beneficial to society, but it's a difference that is
tough on people, which militates against doing things which are long term, and
starting them too soon. It's difficult. He does not have the glamour, if you
want, or the marketing, that will make it likely that my colleagues would accept
him. They wouldn't even involve me because by that time I will be officially
retired. He probably won't be promoted, which means we will lose another six
years. Quite aside from human problems and what have you, if he doesn't stay,
04:24:00you've lost him, and it's also money; you've lost both financially and in momentum.
You don't always do that if you have a system like Harvard, which is built on a
rotation of people through the department. That's okay, but that's not what
we've been doing. Then you'd have to have more than one at the same time. You'd
have to have several. We finally added young people in other areas. We have some
very good inorganic people, one of whom we just lost to Harvard. That's [Charles
M.] Leiber, who was impossible to keep because they really offered him
everything he could want. In fact, they included things that he never thought
of. But he's really very good.
But the only one we have left is outstanding. Gerard Parkin is outstanding.
We're promoting him to tenure now. There is also a young physical chemist; he's
04:25:00outstanding. I don't know what his future will be. We imported a beginning,
middle-aged physical chemist from the University of California, Irvine. He is
[James J.] Valentini. Everybody tells me he is an outstanding experimental
physical chemist, which is probably true. He certainly seems to be an
outstanding person. So we're making progress in getting this ship back into shape.
But we do have a problem, which is a serious one in organic chemistry. Well,
take the field of synthesis and the people that we have left here. Nakanishi
does not really do synthesis as a contribution to synthesis. He may actually
synthesize something; that's different. The good news about the department is it
still has a remarkable range, from touching biological things with Nakanishi, to
04:26:00touching physical chemistry with Turro in photochemistry. In fact, he could just
as well be a physical chemist, but he is an organic chemist. Nakanishi does
organic structure and biological things like the mechanism of vision and things
like that. Breslow does mechanistic biochemistry and mechanistic things, but
also a little synthesis. Katz is not all that much any more and was interested
in a pretty narrow area of organometallic chemistry. Synthesis is where we put
him, when we added him to the staff. It was like when they added Cram at UCLA.
Winstein thought he was adding a natural product chemist, because that's what he
was interested in. But to survive at UCLA you had to do mechanistic stuff
04:27:00because Winstein was overpowering. So in order to show he could do it as well as
the next person, he became, I guess probably to the world's advantage, a
physical organic chemist.
Breslow does not really do synthesis, except in a minor way. Still has now
switched over to very outstanding stuff, there's no question about that, which
deals with modeling, which he was majorly involved in putting out. There's no
question that this place owes a lot to Clark Still. This place has strength and
self-confidence as exhibited by the fact that both Breslow and Still turned down
full professorships at Harvard. That's pretty good, after all, because whatever
Harvard's quality, it can't be that bad. [laughter] So it's not so bad. But it's
04:28:00the renewal part that is bothersome. Still is not that old. I don't know how old
he is, probably more or less Wender's age, I would guess, something like that.
So that is the problem, but how to solve it is not so easy. I mentioned that we
would love to bring Wender here. We would love to bring even half of Danishefsky
here. There is this peculiar deal that he has with Sloan-Kettering, and his
postdocs could stay there doing biochemistry. That's not ideal; it would really
be better to bring Wender here. Or it would be great to bring Overman here; we
tried in fact to bring Overman here. He was willing to come, but his wife likes
California, which many people do, and so she didn't want to move here; she has a
nice job there. Paul Wender also; his wife has a job that she likes,
unfortunately in the administration; she is an assistant dean at Stanford.
04:29:00What's in our favor is that Stanford is in a kind of a minor destabilized
situation because of the trouble with their poor president. And it's possible
that Barry Trost, who's an outstanding chemist, may be driving Wender nuts;
that's conceivable. [laughter] I mean, no reflection on either one, but two
highly motivated people could do that. So there could be some perfectly good
possibility of doing it, but the problem is always one of space.
So we do have problems. These are tough financial times. The university has
already spent an outrageous amount of money constructing whatever they did
construct. The department eventually borrowed money from the university, in the
flippant belief that the university would not collect it back. But the
university in fact is recovering one-tenth of that loan every year from the fund
04:30:00that it gives the department. It was really a loan. We said, "Sure, we'll pay it
back," and they said, "Oh, yes you'll pay it back, because we'll take it out."
We thought we would get the money and then we wouldn't have to give back it to
them. [laughter] This is not the time that it is all that easy to do things, so
there is a concern about the future.
There is a very good thing about Columbia, a major good thing without which we
could not survive. They own a lot of real estate around the place, and it is
possible for both professorial additions and graduate students and postdocs to
be housed at about half the going rate because Columbia makes up the difference.
The counterpart of this is that Columbia does not make as much on its
investments as it ought to because its money is tied up in this non-productive
real estate, which if it didn't have, it wouldn't have anybody. So it's complicated.
It's complicated, but there is New York. New York is great. What makes New York
04:31:00great it's not that you do all these things. I would have no doubt whatsoever if
somebody tells me that they do more, that they go to more ballet, more concerts
and more theatrical productions in Ames, Iowa than they do here. I would not be
surprised at all. It's probably true, because in Ames, Iowa, the ballet company
goes through, you go. [laughter] Here, you just never go. You never go because
it's there all the time. It's like you don't go to see the Eiffel Tower if you
live in Paris. It's there, and you can always go there. I never saw the glass
flowers in Cambridge, Massachusetts. They were next to the chemistry building. I
should go and see the glass flowers. So you could go to this, you could do that.
You know you could. You could just drive down and go. Once in a while we
actually do, but not as often as you might think. For a certain type of people,
and I think it could be true of Paul Wender, that sort of thing is important
04:32:00though not used. It's also expensive, so the counterpart of it is that it's
tough for people. For young people, starting a family here would be tough; tough
or maybe even ridiculous. I'm not sure which. They can live outside the city,
but even that is expensive.
BOHNING: Harry Gray was here for a while, wasn't he? But he left quite early, or
he was quite young at the time.
STORK: We sort of established Harry Gray. He came here directly from a postdoc
abroad in Denmark.
BOHNING: That was with [Carl] Ballhausen, wasn't it?
STORK: Yes. He left here to go to Caltech and has remained a friend of the
department. He is the one who sent us Lieber, who's now left us to go to
Harvard, but at least he came here. He's also the one that's contributed to
stealing Jackie [Jacqueline K.] Barton. So I guess it works both ways. So he was
04:33:00here and is obviously an outstanding inorganic chemist.
Another outstanding person who was a shame to lose, but there was nothing we
could do about it, was [Richard N.] Zare. Zare is an outstanding physical
chemist, really outstanding, at Stanford, and is doing very well. He was not
unfriendly to the place. He left on good terms. Let's say it was just an offer
he couldn't refuse. They built him up an entire research laboratory in a new
building. We can't do that, so there is a limitation as to what kind of person
you can get here. This argument that we can succeed in doing something
worthwhile with the organic part of the operation, and now with the inorganic,
if we ever succeed, and possibly biochemistry, by taking people that are quite
young. They get used to being in New York; they learn that it's possible to do
it. But by the time you get somebody who has young children and is established
04:34:00somewhere in the Midwest, and he sees how much he has to pay for a house
here--that's hopeless. So the only place you can get people that will not be
shocked out of their minds would probably be the Boston area or the
California/Berkeley/Stanford area. That's it! Everywhere else, they'll say,
"This is ridiculous. You can't do this." So that makes it difficult. Probably
that is the strongest argument for hiring young people; but then if you do, you
have to be either very lucky, as we were, or a combination of that and special
circumstances. Or you'd have to add several at a time, which we cannot really
very well do. So we have a problem. We have a problem.
BOHNING: What about attracting graduate students?
STORK: I've mentioned two of the most recent graduate students I've had. Well, I
had three at the same time. Two of them are becoming well-known, and the third
04:35:00one is an assistant professor at the University of Arizona. The other two are
Rychnovsky, who has not yet been promoted to tenure, but obviously would be,
certainly within four or five years. The other one is Dan Kahne, who's getting
to be known all over the place. We offered Dan Kahne to move here, but we were
not willing to do what our mind told us was the wrong thing to do, namely to
give him tenure immediately. He would have been an idiot, as I told him, to
accept it. We were right in doing what we did, and he was right in staying
there, especially since that forced Princeton to give him tenure. So he's doing
all right. These people are as good as anyone in the country. As I said, they
both are Presidential Young Investigators.
04:36:00Why they show up here, that's something else again. But we've had extremely good
people, either as postdocs or graduate students. Overman was a postdoc of Ronald
Breslow. Wender and Danishefsky were postdocs in my group and so was Heathcock.
Other graduate students were people like John McMurry at Cornell or Bruce Ganem,
also at Cornell, and [Jeffrey] Winkler at Pennsylvania. These people were
graduate students here, and there are many others who were really very, very
good. Paul Grieco is the one who finished lupeol. Burgstahler hasn't done as
04:37:00much as he should have. He's been a professor at the University of Kansas. There
are no complaints about them. The only complaint conceivable is that once in a
while one has the feeling they could work harder, but that is a feeling we
probably would all have, no matter what they did. So I'm not sure that that's reasonable.
BOHNING: That's an interesting comment, because I've heard that from some other people.
STORK: Yes. You always look back to the good old days. The fact is in the good
old days you had no choice, because unless you crystallized a compound,
distilled it, and purified it, you didn't get anything. That took time. The
operation demanded your presence. Like when you feed rats; you've got to show
04:38:00up, otherwise they will die. So you show up in the middle of the night if you
have to. Today the thing is much more intellectual. You have to think more than
you used to; there's no question about it. You do have this mass spectrometer
data, you do have this NMR data. You have to make something of it. You spend
much less time trying to get this material to crystallize or something like
that. There's much less that's involved in developing technical skill. Anyone
can pretend to be a nurse, as they all do, and inject some stuff through a
rubber septum and then take a spectrum. There's major disaster if it
crystallizes, because then maybe your sponsor will demand that you crystallize
it again and take a melting point. Do we have such a machine? [laughter] It's
different; it's something else. So it's a different game, which requires more
thought; there's more information to digest, and more stuff to learn.
04:39:00It's always true; it more or less almost takes care of itself. The very best
people work the hardest. Dan Kahne and Scott Rychnovsky could have sailed
through with no problem at all working minimally, but they worked hard. Kahne
was in here Saturday and Sunday, all the time; so was Rychnovsky. These people
worked so hard. Why? Because they're very good. Part of being very good is being
very excited about it and so those people work very hard. The ones that don't
work so hard are the ones that rationally should work much harder because
they're not that good, but they probably would never become that good.
[laughter] Still it's frustrating. Once in a while I come in here. Say, it's ten
o'clock in the morning. Nobody. Where are they? One the other hand, another time
I've come in here on Sunday, and they're working. So it's just simply that they
have a different kind of operation.
04:40:00BOHNING: Did you ever have any interaction with Kurt Mislow when he was at NYU?
STORK: Socially only. That is, I know Kurt; I've seen him recently at Princeton.
He is a very, very likable person. He's obviously a very smart person. I don't
understand why he's fascinated by that complex problem of chirality. I know he's
doing it extremely intelligently because he's that kind of a person. I don't
emotionally relate to it. The apple business is interesting. He's interested in
the mathematics of cutting an apple. You know what they say, that if you cut an
apple in a certain way, which was worked out long ago, the so-called coupe du
roi, which was initially done in the French king's household by someone, you get
two particular pieces, if you do the cut right. I've massacred so many apples
04:41:00because of Mislow. [laughter] But the fact is, you get two pieces which are
obviously both the same absolute configuration and you put them together and it
produces an achiral apple. The question is, how can you mix plus with plus and
get dl? It's obviously intellectually a very interesting problem, and that one I
relate to, to some extent, because I can understand it and I've seen these
pieces of apple. [laughter] But otherwise, no.
[END OF TAPE, SIDE 12]
STORK: These people are important. Even though what Kahne does is nothing like
what Mislow relates to professionally, Mislow is able to see that Kahne is an
04:42:00outstanding guy. You can judge; obviously I'm biased towards things which I can
understand, like intensity. How much does the guy seems to care? Which is very
related, so that I say, "I know he's a very good physical chemist." What I
really mean is, "He seems to be intensely interested in this stuff, and if he
has some focused drive then I guess he can probably do good things." Now,
whether I would be able to recognize someone who is totally withdrawn and will
be the next Einstein, is highly debatable.
And that's a problem, because obviously the American higher education system is
to some extent focused on the easily recognizable focused drive and enthusiasm,
which is important. It's certainly important in "making it." Whether in the
process we eliminate people who would become very important, I don't know.
04:43:00Whether it matters, I don't know. One can argue that if they end up in industry,
so what? That's a perfectly good place; there's nothing wrong with that. Whether
they're diverted to become second rate lawyers, that's more serious, if it
should be happening; maybe it doesn't happen.
I know at least one who became a patent lawyer, through no fault of his own, and
would have been one of our outstanding chemists. What happened to Conroy was his
own fault. What happened to Conroy I mentioned before.
Whatever this little book on Woodward says, Woodward originally had no use for
x-rays. The reason for that was that in the early
days of x-ray structure, Woodward knew the structure of penicillin and
strychnine before Dorothy Crowfoot determined it. So it was easy for him to
04:44:00become convinced that there was a good chance that these people could not figure
out what it was with their x-rays, unless they already knew what it was, which
he held onto. Now, the physics of x-rays is such that this makes no sense
whatsoever, but that was not involved. You see, they were suspicious.
But then, one of the first times that the situation was clearly reversed,
involves a structure that Harry Conroy became interested in. It was different
with tetracycline. Woodward figured out the structure of tetracycline before
x-rays. So that all added up. Conroy was very much interested in an alkaloid
called gelsemine. Gelsemine has a certain structure, and Conroy, fresh from the
great achievement of the structure of picrotoxin, dealt with gelsemine. He made
one mistake. One connection was wrong, which was painfully made clear by the
04:45:00x-ray structure. The x-ray was correct, and that shook Conroy very much.
Structure solving was what he loved. Somebody was stealing his girlfriend. He
just gave up organic chemistry altogether and decided to become a quantum
mechanician. Now, that shows how smart he was. How many organic chemists can
switch to doing quantum mechanics? He locked himself up at Yale for two years,
just showed up to teach his course. He taught himself quantum mechanics,
inventing methods. I've talked to [John A.] Pople about it, because I couldn't
believe it. It's one thing to love quantum mechanics, but it's another thing to
actually make any kind of contribution. Pople said, "No question about it." He
said there was this type of differential equation or integral equation that
wasn't solved until Conroy became the first one to show that you could do this
04:46:00by using Monte Carlo methods. (These are words for me; I don't know what they
mean.) He was the first one to produce ab initio the energy surface for a
three-electron system, when before that it had only been done for two electrons.
My feeling is that what Conroy did is fabulous, but there is no way that you can
have extended the method to any real molecules. It was an incredible achievement
to do this [before computers] with three electrons. It's really fantastic.
Eventually, Yale tossed him out because they said they had hired a person that
they thought would be a synthetic chemist, and there they had a half-baked, so
far as they could tell, or half-believable, certainly not believable, quantum
mechanician on their hands. They could not give him tenure.
And at that point, Bothner-By, whose name came up before, was at what was at
04:47:00that time the Mellon Institute. He knew Conroy when he overlapped with him at
Harvard. He offered Conroy a permanent position on the Mellon Institute staff as
a quantum mechanics person. It took tremendous courage. Conroy slowly came to
the realization that his approval did have limitations, and that he could only
go so far. If Conroy had become interested, let's say, in x-rays, he would have
probably have made great advances in x-rays, with the combination of what he
knew. But he was damaged psychologically by x-rays and could not forgive them.
He went to MIT for a postdoc for a sabbatical year, trying to get interested in
problems having to do with biology or something like that, but he did not get
interested in that. He went back to some complications, because Mellon had
04:48:00merged with Carnegie. They decided that Conroy had to teach, because it was now
a university. Conroy pointed out, quite correctly in my opinion, that he was
hired to be at the Mellon Institute, and he'd be damned if he wanted to teach.
He didn't feel like teaching. Eventually they bought him out, as far as I can
see. I once called Carnegie-Mellon up (and I don't know if it would be true now)
to try to find out where he is, and they denied he was ever there. [laughter] I
mean, they wiped him out in the Russian tradition, the way they used to do with
various people they didn't like. The rumor is that he is a photographer in
Pittsburgh, and that's possible. His father was a press photographer, and he had
some cameras. It's possible that he became a photographer in Pittsburgh. That's
a shame. So that was the story of Conroy.
BOHNING: Well, I've run out of questions at this point, although I know there's
04:49:00more that we could discuss. Is there anything else that you would like to add
04:50:00that we haven't covered?
STORK: Not really.
BOHNING: I appreciate your taking the time to spend the day with me.
STORK: I appreciate your taking the time. I enjoyed it. I guess there's nothing
one likes better than talking about oneself. [laughter]
One of my favorite pets is a reaction that is well known, the Arndt-Eistert
reaction, which has nothing to do with either Arndt or Eistert. That's the only
one I know that you can say that about. It always fascinated me. You can't say
that about the Diels-Alder reaction. [Otto] Diels and [Kurt] Alder really did
04:51:00that. [laughter] Okay. There's a reaction that is called the Birch reduction.
Charles Wooster discovered it, but nobody paid any attention to it because it
was a DuPont patent.
There is also a large ring acyloin cyclization.
BOHNING: Oh, yes.
STORK: Virgil Hansley discovered it.
STORK: It was really quite interesting. I don't know Hansley or Wooster. I've
never met them. All I know is that these patents antedated what made these
academic types famous. That's one.
There's another person whose name I think is John W. Copenhaver. I'm not
absolutely sure. That person was at General Anilined Film and he did reactions,
04:52:00which essentially were what are today called Mukaiyama aldol
reactions. That is a reaction of a cationic species
with an enol derivative. This guy, whose name I probably have wrong, this
so-called Copenhaver (could turn out to be Cooper for all I know) did that like
four years before, with enol ethers, instead of enol thioethers. It's not
terribly different. It's the same kind of thing. That process is used
industrially in parts of some processes to build up vitamin A, by Otto Isler,
Hoffmann-LaRoche, based on what I call the Copenhaver, or whatever his name is,
chemistry. Actually, if I'm going to push this, I've got to find his name.
[laughter] Maybe I'll find his name and send it to you, and you can see if this
These are two names that I can remember. After a while in industry you learn (or
04:53:00maybe it doesn't take very long) that your future and your impact depends on
internal publications and patents and not so much on making it, unless you
intend to leave, with the outside world. That's a difficult thing. I'm sure
there are many other cases of that sort. But these two are good examples,
especially Ainsley. That always impressed me because these are really pretty
important reactions from this guy nobody has ever heard of. [laughter]
Anyway, I have the feeling, because I have seen some list of the people that
you've interviewed for your program, that it was biased completely the other
way; and that is that you mostly interviewed industrial people that made polymers.
BOHNING: Yes, we did have a polymer project that was funded by the NSF, and for
several years we focused only on polymer chemists. That project also produced a
traveling exhibit, Polymers and People, and a small booklet.
[END OF TAPE, SIDE 13]
[END OF INTERVIEW]