00:00:01 25 years ago, actually a little bit less, I arrived at Michael Reeves Hospital after a brilliant postdoctoral fellowship, learning physical biochemistry and realizing that I was not cut out to be a physical biochemist.

00:00:19 So I took a job at Michael Reeves Hospital doing biochemical research with a nephrologist by the name of Victor Pollack.

00:00:26 At that time, Dr. Natelson was two floors up. He said to me, Pesce, what do you do? I said, why do you do research? He said, the grants are going to run out one day and you're going to have to earn an honest living.

00:00:40 So I said, what am I to do?

00:00:43 25 years later, you're still waiting.

00:00:45 I'm still waiting for an honest living. But he said, become a clinical chemist. He said he would teach me clinical chemistry if I spent an hour a day with him.

00:00:53 So I did that for six years, and lo and behold, I became a clinical chemist.

00:00:57 Dr. Natelson...

00:00:58 I forgot to say that I sprinkled the holy water on him, too.

00:01:01 That's right. He sprinkled water on people and made them clinical chemists. This is all part of the ritual.

00:01:06 For some reason, I said, I sprinkled water on Brian Collin, toxicologist, right? When he first came into the laboratory. I haven't sprinkled any water on chemists.

00:01:13 So anyhow, that makes him a toxicologist.

00:01:17 Dr. Natelson was trained as an organic chemist.

00:01:21 Graduated in the middle of the Depression.

00:01:23 When he got his Ph.D., they said, Natelson, congratulations, you're unemployed.

00:01:27 At which point, he taught high school.

00:01:32 He positioned himself with a research company in the 1930s.

00:01:40 He started his own business, but he's about as poor a businessman as I am.

00:01:44 He's never done well in his business ventures.

00:01:47 Then he went off to, but he did make enough during the Second World War to retire after he thought of moving to Rockford, Illinois.

00:01:52 And then, this is basically the story where he is going to start to tell you about what he did in Rockford, Illinois.

00:01:59 Which was the beginnings of pediatric clinical chemistry in the United States.

00:02:03 Here's Dr. Natelson.

00:02:04 Thank you.

00:02:05 I want to thank Dr. Pesci.

00:02:09 Because I had forgotten about this material.

00:02:12 And I realized it was time to recall it.

00:02:15 And you'll see, when I'm finished, why I say that.

00:02:19 I was, you got one part right.

00:02:23 In 1931, I had my unemployment certificate.

00:02:27 It said Ph.D., re-employment certificate.

00:02:29 But that's what it was.

00:02:30 It was an unemployment certificate.

00:02:32 It meant that I ceased to be a teaching fellow, which I had been employed since 1928.

00:02:38 And that I had to go look for a job.

00:02:40 So, I went to the New York testing labs.

00:02:42 They had no room.

00:02:44 And I became a consultant chemist in the industry.

00:02:47 They gave me space because they had no business.

00:02:50 And they said, go find a business.

00:02:53 Well, one of my clients was a person who wanted a plastic with high electrical resistance.

00:02:59 So, I made styrene resins for him.

00:03:02 And I have a letter home which says, there is no future for styrene resins.

00:03:08 Of course, some of the questions called for those.

00:03:11 On the other hand, I published it, therefore, in the Industrial Engineering Chemistry.

00:03:17 In 1950, I received an award for the ACS as the most significant paper in the first 50 years.

00:03:24 So, you can see I was a pretty well-known organic chemist.

00:03:28 And along came a man by the name of Benjamin Cramer.

00:03:31 Benjamin Cramer was an interesting person because he had a math degree

00:03:36 from the University of Indiana in chemistry.

00:03:40 And he was appointed the first clinical chemist.

00:03:44 They didn't call him clinical chemist.

00:03:46 At Johns Hopkins University to run the laboratory.

00:03:49 And what was the laboratory doing mostly?

00:03:52 Looking for methods for doing calcium regeneration.

00:03:54 Because your floors were loaded with kids with the English disease.

00:03:59 The English disease, the English conkite, was rickets.

00:04:05 And I lost two of my brothers in looking up their death certificates.

00:04:10 The age of two, apparently, died of rickets.

00:04:15 And it says English disease on the death certificate.

00:04:19 When Benjamin Cramer came into my laboratory, he had a problem.

00:04:25 He had developed a technique of giving strontium to these rickety children.

00:04:30 That decalcified them.

00:04:32 Then he straightened out their bones.

00:04:34 And then he gave them calcium.

00:04:36 The only trouble was, he couldn't get the calcium into them.

00:04:39 He had to give it intramuscularly or intravenously using calcium glucate.

00:04:45 Calcium carbonate wouldn't dissolve.

00:04:47 It wouldn't go into them.

00:04:48 Calcium phosphate wouldn't go into them.

00:04:50 And the calcium, and several others.

00:04:53 In the meantime, I worked out a method for doing strontium and calcium in the same serum.

00:05:00 He was the famous Cramer-Tisdall method for calcium.

00:05:04 Tisdall was also a chemist out there.

00:05:07 Which later on became the Clark-Collip method.

00:05:10 The modification that Clark-Collip was, Cramer used one cc of serum.

00:05:14 Clark-Collip used two cc of serum.

00:05:17 That was the modification.

00:05:20 But the interesting thing was, Cramer showed me a letter which said,

00:05:26 this author proposes to analyze one cc of serum for calcium.

00:05:34 There's no way in which he could possibly do that.

00:05:37 And there's some papers you really can't.

00:05:39 So he framed that and hunkered up on his wall.

00:05:42 And of course, that's why he came to me.

00:05:46 I had gotten my Ph.D. with a student at Pradles who had taught me microchemistry.

00:05:50 And I had published several papers on microchemical organic analysis.

00:05:55 And that's how he came to recommend it to me.

00:06:00 And finally, he offered me space at the Jewish Hospital in Brooklyn, New York.

00:06:04 Gave me 5,000 square feet.

00:06:06 Which I did my consulting work without pay from him.

00:06:09 And I was consultant in the department of pediatrics.

00:06:12 And my first job was to find a way to get calcium into these kids.

00:06:17 And I had a client for whom I had made adenosine triphosphate.

00:06:24 He sold it under the name of MYBDEN, M-Y-B-D-E-N.

00:06:29 He sold it as a proprietary for pepping people up.

00:06:33 And it's an interesting report because when I was at Brockford,

00:06:37 I had a man on IV fluids for 54 days.

00:06:40 And he wouldn't wake up.

00:06:42 And I started shooting him with MYBDEN

00:06:44 because I measured his red cell ATP level.

00:06:47 It was very low.

00:06:48 I raised his ATP level and he aroused.

00:06:51 It was a very interesting drug.

00:06:53 But anyway, in making ATP, you've got to involve,

00:06:56 you've got a nuisance of the other.

00:06:58 Then you've got to precipitate,

00:07:00 which turned out to be calcium fructose triphosphate.

00:07:03 If you put yeast on, let's say, glucose or some glucose source,

00:07:10 it will phosphorylate the glucose,

00:07:14 convert it to the glucose fructose triphosphate,

00:07:17 then split it in the middle.

00:07:19 Now you can make it split in the middle completely.

00:07:23 I mean stop that splitting in the middle

00:07:25 by adding a little bit of iodoacetic acid.

00:07:28 It's an inhibitor for aldolase.

00:07:30 And then you add a little calcium

00:07:31 and you get a huge precipitate

00:07:33 and you have it by the gallon or by the pound.

00:07:36 So I took the calcium fructose triphosphate,

00:07:38 and I reasoned this way,

00:07:40 that since calcium could be absorbed with milk,

00:07:44 it was absorbed as a phosphate attached to a polypeptide.

00:07:48 And to find that calcium phosphate polypeptide out of milk

00:07:52 was a tough job.

00:07:53 I figured I'd try calcium fructose triphosphate.

00:07:56 And I did.

00:07:57 And that's essentially the subject of the first slide.

00:08:01 May I have the...

00:08:03 Oh, yes, let's see.

00:08:12 You have a slide that says this.

00:08:16 Outcome of Nielsen's Pediatric Studies.

00:08:19 And I put this because my pediatric studies ended in 1958

00:08:24 when I left Boston.

00:08:26 That's why I was blackballed by all the physicians.

00:08:29 Prematures and full-time infants

00:08:31 are now monitored by signs of dehydration

00:08:34 and blood controls especially,

00:08:36 hematopoietic electrolyte,

00:08:38 pH of blood,

00:08:39 on a routine basis.

00:08:42 As a result of this,

00:08:47 there are 1.8 million people alive today

00:08:50 who would not have been alive if this had not developed.

00:08:54 In any pediatric department in the world,

00:08:56 it looked like the pediatric department

00:08:58 that I had set up in Boston.

00:09:00 Milk formers are now designed

00:09:02 to simulate the composition of breast milk.

00:09:04 I'll prove that.

00:09:06 What had happened was

00:09:08 the pediatricians were practicing medicine

00:09:10 just the way they did in medieval days.

00:09:12 They never measured anything.

00:09:14 They got the impression that something would work,

00:09:17 but they bled President Washington.

00:09:20 When he didn't respond,

00:09:22 they bled him some more.

00:09:23 All they had to do was take a hematopoietic

00:09:25 and found out that he was probably anemic.

00:09:28 Anyway, they killed him.

00:09:30 Milk formers are now designed

00:09:33 to simulate the composition of breast milk.

00:09:35 Starch hydrolysis is completely painful.

00:09:38 I'll demonstrate that I developed that.

00:09:41 I had a pH meter.

00:09:44 I measured the pH of these children

00:09:46 on high-protein milks.

00:09:48 They were in acidosis.

00:09:49 I measured their urea levels.

00:09:51 Their urea was 30 and 40,

00:09:53 while on breast milk they had urea of 6 and 7 and 8.

00:09:56 There was no question that the high-protein milk

00:09:58 was causing an acidosis

00:10:00 and putting a load from getting rid of the nitrogen

00:10:02 on the infant.

00:10:04 When that happened, I made an enemy.

00:10:07 The man who was the protagonist of high-protein milks

00:10:10 was Charles Levine, who was at Hopkins.

00:10:13 He was the chief consultant

00:10:16 to Similac and a number of other companies.

00:10:19 I said that what he was making was garbage.

00:10:22 That, of course, didn't make him very friendly with me.

00:10:26 He was the editor of the journal Pediatrics.

00:10:29 I never got a paper published there again.

00:10:31 As a matter of fact, my assistant tried to publish a paper there

00:10:34 saying that, confronting some of the work I had done,

00:10:37 that teenagers and newborns have high hematopoietic risk.

00:10:40 He wrote out a letter, which I read,

00:10:42 which said,

00:10:43 Nadelson's work is unreliable.

00:10:45 I'll publish this if you don't refer to Nadelson.

00:10:49 Dr. Menard said, Michael, he says to me,

00:10:52 Nadelson, everybody knows that you somehow or other

00:10:57 have to do with the survival of prematures.

00:11:00 But when I look in the literature for a reference,

00:11:02 I can't find any.

00:11:03 I can't find any either.

00:11:05 No one would publish my paper.

00:11:07 Calcium administration is now carried out exclusively

00:11:11 with chelated calcium carbonate, especially with heptophosphates.

00:11:14 I didn't know how important that was

00:11:17 because when they took this calcium fructose diphosphate

00:11:21 and fed it to these McKinney kids,

00:11:23 all of them didn't have rickets.

00:11:25 A number of them had been given vitamin D.

00:11:27 We didn't have vitamin D,

00:11:29 but we did have cod liver oil concentrates,

00:11:32 and I made a lot of it.

00:11:34 And some of them would not respond to cod liver oil.

00:11:38 But if you gave them calcium fructose diphosphate,

00:11:41 it would absorb.

00:11:42 So calcium fructose diphosphate somehow or other,

00:11:45 and it's never been clarified,

00:11:46 is involved in the absorption of calcium from the gut.

00:11:50 I still believe that.

00:11:56 Dr. Kramer came to me and said,

00:11:58 Nadelson, you missed getting your name in headlines

00:12:01 by just a little.

00:12:02 I said, what do you mean by a little?

00:12:04 He said, if vitamin D didn't become available in milk,

00:12:08 everybody would be using calcium fructose diphosphate

00:12:10 to cure rickets.

00:12:12 Let me have the next slide, please.

00:12:15 I'm talking to myself.

00:12:16 Okay, there it is.

00:12:18 It's okay.

00:12:20 Now, what this shows,

00:12:22 demonstrates two things.

00:12:24 What the clinical chemist is doing at that time,

00:12:27 he's working with a physician,

00:12:29 getting the problem,

00:12:30 going to the laboratory and solving it,

00:12:31 and going back and working with the physician again.

00:12:34 Here, this is published in General Clinical Investigations,

00:12:38 just before I became an outlaw.

00:12:40 Change in serum levels after administration

00:12:43 of six grams of calcium fructose diphosphate.

00:12:45 These are all volunteers.

00:12:47 Now, the easiest animal to do research with is the human.

00:12:51 He's intelligent, somewhat odd anyway,

00:12:54 and he will follow directions,

00:12:57 and you can get plenty of blood from him,

00:12:59 and you can get him to do all kinds of things.

00:13:02 But if he tried today,

00:13:04 you'll be sued for everything you've got.

00:13:07 Some lawyer will find out, and they'll sue you.

00:13:10 So, this will be impossible today.

00:13:12 Now, I would like to call something to your attention.

00:13:15 When they get calcium fructose,

00:13:17 the organic phosphate was 0.6, 0.4, 0.4, 0.6, 1.2, 1.1.

00:13:23 Then, it goes up to 3.4.

00:13:27 So, 3.4 is about between 5 and 6 times 0.6.

00:13:33 Tremendous rise, and with the fructose diphosphate,

00:13:36 it goes in, and in so doing, it pulls in the calcium.

00:13:39 Now, let's see the calcium growth.

00:13:42 Where is the calcium growth?

00:13:45 I don't see it.

00:13:47 It disappeared.

00:13:49 Oh, here it is, right over here.

00:13:51 Now, you notice 10.1 and 10.3, 10.4.

00:13:55 Well, you say there's no significant difference,

00:13:58 but look at every single case.

00:14:00 The calcium is going up.

00:14:02 Now, it's very difficult to change the calcium

00:14:05 when your calcium level is normal.

00:14:07 If you raise the calcium,

00:14:09 calcitonin will knock it into the bones.

00:14:11 You lower the calcium, paracetamol will pull some out.

00:14:14 So, here we're fighting that mechanism,

00:14:16 and we're getting this.

00:14:17 Now, how significant is this?

00:14:19 There's a big difference between the technicians

00:14:21 in 1932 and 1933.

00:14:25 This was probably in 1948 at that time.

00:14:28 First of all, every technician had to have

00:14:30 a bachelor's degree in chemistry

00:14:32 with a major in analytical chemistry.

00:14:35 Secondly, the methods were done gravimetrically or by hand.

00:14:40 For example, when you do a carbon-hydrogen today,

00:14:43 you've got to report 86.23% carbon.

00:14:47 If you report 83.73%,

00:14:51 they will not be acceptable.

00:14:53 So, in a clinical lab,

00:14:56 if you report 80% and 90%,

00:14:58 whether it's a sugar of 80% or 90%,

00:15:00 it doesn't make any difference.

00:15:01 That's why the modern machinery

00:15:04 has degraded, repeatedly,

00:15:07 the accuracy and the reproducibility.

00:15:10 They're reproducible, but not accurate.

00:15:14 But in those days,

00:15:16 what this calcium method was this.

00:15:18 Kramer had titrated calcium oxalate with permanganate.

00:15:22 He changed the method to ash the oxalate

00:15:27 and then tied it with acid,

00:15:28 because acid-dimetric titration was more accurate.

00:15:31 And I can tell you this.

00:15:33 These technicians would do every one of these in triplicate,

00:15:36 and this would be 10.3, 10.25, and 10.3.

00:15:40 And, therefore, this would definitely be significant

00:15:42 when you don't need a statistician.

00:15:45 When every result was exactly in the same direction,

00:15:49 it is significant.

00:15:50 May I have the next slide, please?

00:15:54 This one here also shows the same thing.

00:15:57 These are more of the same patient.

00:15:59 I have 12 of this.

00:16:01 This one went to 8.1, 8.5,

00:16:03 then a little lower here.

00:16:06 But, of course, in those days,

00:16:07 we also had to have control.

00:16:09 May I have the next slide, please?

00:16:12 Now, in back of this,

00:16:14 this is the summary of all the data.

00:16:16 This is the calciums.

00:16:18 This is the phosphorous.

00:16:21 It shows the same thing in calcium.

00:16:23 That's also under control.

00:16:25 And the organic phosphates,

00:16:30 that's citrate,

00:16:32 which is not relevant to what we're talking about.

00:16:35 Next slide, please.

00:16:37 Lower left.

00:16:38 Now, below here.

00:16:39 Here, well,

00:16:40 we have a little bit of the fastened,

00:16:43 but centralized over fastened.

00:16:47 You'll see here,

00:16:48 there's a very big number over here.

00:16:50 It's the last row.

00:16:51 Centralized over fastened organic phosphates.

00:16:53 There's 173%.

00:16:55 There's no question about it.

00:16:56 It's right.

00:16:57 And when you watch these children,

00:16:59 one shot,

00:17:00 six grams or three grams,

00:17:02 they'll give them calcium phosphate.

00:17:04 Then they want to go home,

00:17:05 because their calcium level is measured.

00:17:07 If you have a calcium of five,

00:17:09 and you give calcium of five,

00:17:11 it becomes a 10 right away.

00:17:13 If you have a 10,

00:17:14 it's very hard to get it off the 10.1.

00:17:18 So, I didn't see very much of this work,

00:17:21 and I forgot about it,

00:17:23 until about 20 years ago,

00:17:24 I got a call from one of our society,

00:17:28 saying that they had cited this paper

00:17:30 as being probably one of the most important papers in calcium.

00:17:33 Calcium absorption.

00:17:35 And all of the preparations that have calcium,

00:17:40 oral calcium,

00:17:41 are hexose phosphates today.

00:17:44 May I have the next slide, please?

00:17:49 What this is,

00:17:50 you have to have a control.

00:17:51 So, I needed something that was identical

00:17:54 to what we were doing.

00:17:55 Fortunately, the Ice Bishop Company

00:17:58 made this material in two forms.

00:18:01 They made a hydrate,

00:18:02 and they also made an anhydrous.

00:18:04 The anhydrous was stable.

00:18:05 The hydrate was not.

00:18:06 So, I got from them,

00:18:08 a nine-month-old hydrate,

00:18:11 which was completely hydrolyzed.

00:18:13 It had no calcium,

00:18:15 fructose,

00:18:16 or phosphate in it.

00:18:17 The water was calcium,

00:18:18 phosphate,

00:18:19 and fructose,

00:18:20 that's mostly.

00:18:21 And it didn't work.

00:18:22 In other words,

00:18:23 let's look at the organic phosphate.

00:18:25 And you see,

00:18:26 there was practically no,

00:18:28 in other words,

00:18:29 0.6 to 0.8.

00:18:31 In other words,

00:18:32 instead of 173% brine,

00:18:34 you had maybe a fraction,

00:18:36 a very small percentage,

00:18:37 not significantly.

00:18:38 So, that was the control,

00:18:39 showing that the phosphate organic

00:18:41 was being absorbed as a whole.

00:18:43 And you have to have chelate

00:18:45 in order to absorb calcium.

00:18:47 And that's why it amuses me.

00:18:49 You take Tums.

00:18:50 All the Tums you take,

00:18:51 calcium carbonate appears in the stool.

00:18:53 None of that is absorbed.

00:18:55 You take bone,

00:18:57 we tried ground bones.

00:18:59 They sell that

00:19:00 at $10 a bottle now in health stores.

00:19:02 You eat,

00:19:03 you take a pill of ground bones,

00:19:05 it's supposed to help,

00:19:06 you know,

00:19:07 that's why,

00:19:08 you know,

00:19:09 what do you call it?

00:19:10 Hypocalcemia,

00:19:11 the agent,

00:19:12 you know.

00:19:13 That's what it was.

00:19:14 It helps.

00:19:15 I don't believe it.

00:19:17 It just isn't absorbed.

00:19:19 May I have the next slide, please?

00:19:23 Now,

00:19:24 at that point,

00:19:25 when I worked with the milks,

00:19:29 Dr. Kramer gave me a project.

00:19:32 He would come in and sit down,

00:19:33 we would sit down with his staff

00:19:35 and we would decide on a project.

00:19:37 And that was what the clinical chemist was doing.

00:19:39 This was my main job.

00:19:41 My job,

00:19:42 the analysis,

00:19:43 there were technicians that do analysis.

00:19:44 Today,

00:19:45 the clinical chemist does the analysis.

00:19:48 Now,

00:19:51 Dr. Kramer said

00:19:52 that a number of formulas

00:19:54 have been proposed using lactose

00:19:57 in breast molasses and milk sugar.

00:20:00 They all fail.

00:20:01 He said,

00:20:02 you get foul-smelling stools.

00:20:04 Tell me what's in the stool.

00:20:05 Well,

00:20:06 I said,

00:20:07 all the lactose is in the stool.

00:20:08 It's not being absorbed.

00:20:09 I said,

00:20:10 well,

00:20:11 at least 90% of it is.

00:20:12 And the urine is loaded with lactose, too.

00:20:14 But there's no galactose.

00:20:16 And I looked for galactose.

00:20:17 I couldn't find anything.

00:20:18 He said,

00:20:19 there's an amount.

00:20:20 I said,

00:20:21 lactose can't be utilized.

00:20:22 So we did a study

00:20:23 in which we measured

00:20:26 carbohydrate levels,

00:20:27 glucose.

00:20:28 We rarely found any lactose.

00:20:30 And this was raw breast milk.

00:20:34 You have a rise from

00:20:38 about 70

00:20:39 all the way up to 180.

00:20:41 And then it was being absorbed

00:20:44 and utilized.

00:20:46 This is

00:20:48 27 cases or something like that.

00:20:50 I can't read.

00:20:51 But anyway,

00:20:52 if you focus it in,

00:20:53 I'll be able to read the number.

00:20:56 40?

00:20:57 40 cases.

00:20:59 About 40 cases.

00:21:01 This is lactose

00:21:02 added to evaporated milk.

00:21:04 The difference is that this has been heated.

00:21:07 This has not.

00:21:08 Let me show the next slide

00:21:09 and show you that it wasn't the mother's milk.

00:21:12 The milk was raw.

00:21:13 This is raw cow's milk.

00:21:15 In those days,

00:21:16 women would have it

00:21:17 and they were certified milk.

00:21:19 Remember the certified milk?

00:21:20 It's a certified milk.

00:21:22 It's a certified milk.

00:21:23 Remember the certified milk?

00:21:24 It's extinct.

00:21:25 Nobody

00:21:26 doesn't want to make it anymore.

00:21:28 Too much trouble.

00:21:29 And this was the lactose

00:21:32 in pasteurized milk.

00:21:34 Well, I reason this way.

00:21:35 If you pasteurize milk,

00:21:37 what you do

00:21:39 is

00:21:42 heat it until the phosphatase test is negative.

00:21:44 Therefore, an enzyme is being destroyed

00:21:47 which causes

00:21:49 which hydrolyzes lactose.

00:21:52 May I have the next slide?

00:21:53 I want to see what the next slide is.

00:21:56 Now,

00:21:57 this is

00:21:59 milk with lactose.

00:22:01 This is milk with dextrose maltose.

00:22:03 I was using cartose

00:22:04 which is a competitor of milk

00:22:06 which is a starch hydrolyzer.

00:22:08 And it's on this basis

00:22:09 that the Lee Johnson Company made a fortune.

00:22:12 Lactose was out.

00:22:14 And from then on,

00:22:15 every formula had to have dextrose maltose

00:22:17 or cartose.

00:22:20 I didn't get anything of it.

00:22:22 Not only that, but I got severe criticism

00:22:24 from Lee Johnson.

00:22:26 I said to them,

00:22:27 why do you criticize me?

00:22:28 They said, because

00:22:29 all the doctors

00:22:31 who we talked to

00:22:32 are up in arms

00:22:33 because you, Nagelson,

00:22:34 are publishing papers in medicine.

00:22:36 And, you see, they didn't realize

00:22:38 that that's standard practice in Europe.

00:22:41 France has no publishing papers in medicine,

00:22:43 you might say.

00:22:44 And Vilan,

00:22:47 I was in his house,

00:22:48 in Germany,

00:22:49 he got the Nobel Prize,

00:22:50 he was a clinical chemist,

00:22:52 for what he did on diabetes.

00:22:54 In this country we had Bloor,

00:22:56 who was Van Slyke,

00:22:59 who was publishing papers in medicine.

00:23:01 And Somogyi was publishing papers on diabetes.

00:23:05 That was the clinical chemist in those days.

00:23:08 Now, this is a very interesting thing

00:23:11 because I, therefore,

00:23:14 proceeded to analyze

00:23:17 this high-pro milk

00:23:18 to see what the problem was

00:23:20 because I wanted to make

00:23:21 an artificial formula, too.

00:23:23 And the first thing I knew

00:23:25 was that in casein,

00:23:27 the lactalbumin ratio

00:23:29 was 4 to 6,

00:23:30 while in breast milk

00:23:31 it was 82 to 18.

00:23:33 In other words,

00:23:35 in cow's milk

00:23:38 it was four times as much casein as albumin,

00:23:41 while in human milk

00:23:43 there was less casein.

00:23:45 And if you sit down and figure out

00:23:47 the percentage of body weight

00:23:49 with bone,

00:23:50 that's what it checks out to be.

00:23:52 The more bone you have,

00:23:53 the more casein.

00:23:54 This was a study which led me

00:23:56 to believe that a calcium fructose

00:23:58 diphosphate idea

00:24:00 because I figured that the calcium

00:24:02 was being absorbed by the casein.

00:24:07 Now, when I went to Rockford,

00:24:09 and I'm getting ahead of my time a little,

00:24:12 I went to the Dean Milk Company

00:24:14 when I was there,

00:24:16 and talked them into spending $50,000

00:24:18 to build two formulas.

00:24:20 One, which is 60% albumin,

00:24:24 they call it non-casein protein,

00:24:26 and the rest 40% casein.

00:24:29 And the other one was 11% albumin

00:24:32 and 89% casein.

00:24:35 Those were the two different formulas.

00:24:37 And you'll see what they did.

00:24:39 And it was breast milk.

00:24:40 Now, you'll notice that

00:24:42 these formulas contained

00:24:44 naturally 3% protein.

00:24:47 I made it 2%

00:24:49 to give them advantage.

00:24:51 Breast milk was only 1.42%

00:24:54 in the first seven days.

00:24:56 How did I get these numbers?

00:24:57 I went around to the mothers

00:24:58 and collected their milk

00:24:59 and analyzed it.

00:25:00 Now, you don't see that data

00:25:02 very often.

00:25:04 The pediatricians would not do it.

00:25:06 It took a chemist to do it.

00:25:08 Let's have the next slide.

00:25:13 Now, when I fed these to the babies,

00:25:17 this is their protein level,

00:25:19 I realized that breast milk

00:25:20 was the ideal,

00:25:22 and the casein formula

00:25:23 was producing more protein,

00:25:25 and the albumin,

00:25:27 and this is more or less evidence,

00:25:29 that the albumin is the source

00:25:31 of plasma protein and not casein.

00:25:33 May I have the next slide?

00:25:34 Casein is a calcium carrier.

00:25:37 Now, all of the work

00:25:38 that was being done by,

00:25:39 as Charles Levine, for example,

00:25:41 I criticized him,

00:25:42 and that's why he didn't like me,

00:25:44 was the fact that they took

00:25:46 the first weight,

00:25:48 and they measured the rate of gain

00:25:50 up to the, oh, maybe tenth day.

00:25:53 Now, this is the worst place

00:25:54 in the world to do a research study.

00:25:57 In this study that cemented the idea

00:26:00 that high-protein milk

00:26:01 was good for children,

00:26:03 there were six cases,

00:26:04 three girls, three boys.

00:26:06 I averaged the weight

00:26:07 of the three girls

00:26:08 was heavier than the weight

00:26:09 of the three boys.

00:26:10 Well, the statistics was nonsense,

00:26:12 and when I published the paper

00:26:14 with Benjamin Cramer's name on it,

00:26:16 of course, I had to use

00:26:18 Benjamin Cramer to protect me.

00:26:22 Charles Levine was furious.

00:26:24 He was just furious.

00:26:25 May I have the next slide, please?

00:26:29 Now, this is a demonstration

00:26:31 that a high casein formula

00:26:33 results in high urea.

00:26:34 This is urea.

00:26:36 In the case of high-protein milks,

00:26:38 this is 2% work.

00:26:39 The urea would be way up there.

00:26:41 May I have the next slide, please?

00:26:45 This shows how stupid it is

00:26:47 to measure weight gain

00:26:49 in the first two days.

00:26:50 This is breast milk

00:26:51 where the mother's not putting

00:26:52 out any milk

00:26:53 until she starts putting out

00:26:54 the full flow

00:26:55 about seven days.

00:26:56 It was very little,

00:26:57 and therefore her baby,

00:27:00 the formula intake

00:27:01 was practically nil,

00:27:03 mostly getting glucose and water,

00:27:05 and this is when you give them

00:27:07 an artificial formula.

00:27:08 May I have the next slide, please?

00:27:11 Now, in order to do this work,

00:27:14 I had to have methodology.

00:27:17 A lot of this methodology

00:27:18 was developed in Brooklyn

00:27:19 before I came to Roth.

00:27:21 And this tube here

00:27:23 is open on this end.

00:27:25 You notice it has no rubber

00:27:27 attached to it,

00:27:28 but all you do is...

00:27:29 Incidentally, that's the wrong place.

00:27:31 You puncture it back here.

00:27:33 All you do is let the blood

00:27:35 run in by itself.

00:27:38 And then...

00:27:39 Let me have the next slide.

00:27:43 And then I would use

00:27:44 the sealing wax

00:27:45 to seal the end.

00:27:47 Here are those

00:27:48 that are already sealed as well.

00:27:49 And then centrifuge.

00:27:50 Next slide.

00:27:52 And then I would measure

00:27:54 the hematocrit,

00:27:55 which you got for nothing,

00:27:57 without wasting any material.

00:27:59 Go ahead, next slide.

00:28:01 And then I would cut the tube,

00:28:04 and you see there's air

00:28:06 coming in from this side,

00:28:07 and just let it flow

00:28:09 into these solid pipettes,

00:28:11 various types of pipettes,

00:28:13 and do all my tests.

00:28:15 May I have the next slide, please?

00:28:17 I could also sample the red cells

00:28:20 for purposes like doing ATP

00:28:22 in the red cell,

00:28:23 things like that.

00:28:24 May I have the next slide?

00:28:26 And then I developed

00:28:28 this microgasometer.

00:28:29 One of the doctors,

00:28:31 his name was Rourke,

00:28:33 he said to me,

00:28:34 Nielsen, you can have

00:28:35 all these methods,

00:28:36 but you're not going to develop

00:28:37 a micromethod to seal tube.

00:28:39 So I did.

00:28:40 And this is the microgasometer,

00:28:42 the Nielsen microgasometer.

00:28:43 People know Nielsen

00:28:44 not for what he did

00:28:45 for prematures,

00:28:46 or they know him

00:28:47 for the methodology,

00:28:49 which is nonsense.

00:28:50 None of this methodology

00:28:51 is in use today.

00:28:53 And anybody who goes about

00:28:54 and spends his lifetime

00:28:55 developing methodology

00:28:57 is not looking ahead

00:28:58 to the future.

00:28:59 If you use the methodology,

00:29:01 if you develop methodology,

00:29:02 you're not doing it

00:29:03 for the methodology,

00:29:04 you're doing it for a purpose.

00:29:05 Here I'm putting the serum

00:29:07 from this open tube

00:29:08 into here,

00:29:09 so I can sample it

00:29:10 into the microgasometer.

00:29:11 Next slide.

00:29:14 This plunger moves

00:29:15 back and forth.

00:29:16 And if you look at it

00:29:17 very carefully,

00:29:18 you'll see that all I did

00:29:19 was take the old

00:29:20 Van Slyke apparatus,

00:29:21 where he had leveling bulbs,

00:29:23 replace it with a plunger,

00:29:25 and make everything smaller,

00:29:27 and that was the microgasometer.

00:29:29 So you can print Van Slyke

00:29:30 where this is more than me.

00:29:32 Next slide.

00:29:34 Now, I had to develop methods

00:29:38 for 10 microliters or less.

00:29:41 That's routine today.

00:29:42 Remember, in those days,

00:29:44 that was considered insane.

00:29:46 Some of the people

00:29:48 who criticized my work

00:29:49 with due respect to Nielsen,

00:29:51 one fellow wrote,

00:29:53 I just don't believe

00:29:55 these results with micromethods.

00:29:57 They're absolutely unreliable.

00:29:59 Anyway, I had this long cuvette

00:30:02 made for the Coleman

00:30:03 with respect to the dominant.

00:30:05 Now, this was for the Coleman,

00:30:07 and this was for the Clem,

00:30:09 using the long cuvette,

00:30:11 using the principle

00:30:12 of getting more color.

00:30:13 Next slide.

00:30:17 Here I'm sampling

00:30:18 with a microgasometer.

00:30:19 Next slide.

00:30:23 Also, I had a friend

00:30:26 in the Bronx

00:30:27 at the Farrand Optical Company

00:30:29 who was an expert in light,

00:30:31 and he was the one

00:30:32 who developed the interference look.

00:30:34 An interference look

00:30:35 is two pieces of glass

00:30:37 with a little glue in between,

00:30:38 and you push them together,

00:30:40 and a distance between the two

00:30:43 determines what color goes through.

00:30:45 The color goes through,

00:30:46 back and forth,

00:30:47 and if it's of the order

00:30:48 of a certain wavelength,

00:30:49 that wavelength will be taken out

00:30:51 or will be reinforced.

00:30:53 So you have what is known

00:30:54 as an interference look.

00:30:56 This is the absorption spectrum

00:30:58 in a vacuum of the urea color.

00:31:02 Here is the interference filter

00:31:04 cutting out this percentage

00:31:06 of new light,

00:31:07 and here is the ordinary

00:31:08 class filter,

00:31:09 which is just colored glass.

00:31:11 And you can see

00:31:12 that you're increasing specificity.

00:31:14 You know, let's call this

00:31:15 white area,

00:31:17 which you're actually reading,

00:31:18 oh, say, at 90%,

00:31:20 and here you've got about 50%,

00:31:23 so you've increased your sensitivity

00:31:26 by a factor of at least two

00:31:28 by using an interference look

00:31:29 with no extra effort

00:31:30 in the methodology.

00:31:32 May I have the next slide?

00:31:33 Of course, that's routine today.

00:31:35 Now, these micro-cuvettes

00:31:37 were not available in those days.

00:31:39 I had a fellow at Glasgow,

00:31:41 by the name of Cop,

00:31:42 but he made them for me,

00:31:43 and at that time,

00:31:44 this was quite a sensation

00:31:46 to line up the spectrum together,

00:31:48 but I'm sure anybody

00:31:49 who worked in those days

00:31:50 struggled to line up these cuvettes

00:31:52 and you can see,

00:31:53 I have one of,

00:31:54 I have one,

00:31:55 the same mic pass,

00:31:57 the reading would be the same

00:31:58 for all three,

00:31:59 but this,

00:32:00 you need three and a half cc,

00:32:02 and this will be only a half cc.

00:32:04 That's five times the sensitivity.

00:32:06 May I have the next slide, please?

00:32:09 And here's the setup

00:32:10 with all the solutions,

00:32:11 including the solution

00:32:13 that went into the flame photometer

00:32:14 and so on.

00:32:16 That's the setup for one kid

00:32:18 for one day.

00:32:19 May I have the next slide?

00:32:22 Now, one of the things I discovered,

00:32:25 Benjamin Kramer,

00:32:27 he kept telling me,

00:32:29 alkalosis is a condition

00:32:31 produced by resonance.

00:32:32 He said,

00:32:33 if you give bicarbonate,

00:32:35 you're sure to end in alkalosis

00:32:37 because you can't control it.

00:32:39 I learned how to control it.

00:32:41 I learned how to control it

00:32:43 by building a pH meter

00:32:45 and plotting

00:32:47 and then calculating both,

00:32:49 I did both of them.

00:32:50 For example, here,

00:32:51 we've given 20% of the bicarbonate

00:32:54 that a kid needs,

00:32:56 and there's no change.

00:32:58 The pH is 6.9,

00:33:00 no change in pH significantly.

00:33:02 40%,

00:33:04 and the pH is still 7.05.

00:33:07 60%,

00:33:09 and the patient says,

00:33:10 at this point,

00:33:11 the doctor will call down

00:33:12 and say,

00:33:13 you people don't know how to do pHs

00:33:15 because that's what they would tell me.

00:33:16 I've given a huge amount of material

00:33:18 and the pH has gone away

00:33:19 from 6.9 to 7.05,

00:33:21 but now,

00:33:23 when you get to 80%,

00:33:25 you've got a pH of 7.25,

00:33:29 which is still acidosis,

00:33:31 but now if you give the rest of it,

00:33:33 the 20%,

00:33:34 it shoots right up.

00:33:35 All you have to do

00:33:36 is give 10% more

00:33:37 and you're up to a pH of 7.6.

00:33:39 Now you see why alkalosis

00:33:41 is very easy to do with bicarbonate,

00:33:43 but I wasn't afraid of bicarbonate

00:33:45 because I knew that lactate didn't work

00:33:48 and why did I know that lactate didn't work?

00:33:50 Because I had a piece of filter paper

00:33:52 and I dipped it in the

00:33:58 sodium lactate

00:33:59 and it turned red.

00:34:00 The liquid was paper.

00:34:01 So I called the company and said,

00:34:03 how come your sodium lactate is acid?

00:34:05 Oh, we put an extra lactic acid

00:34:07 as a preservative

00:34:09 and then I found that all lactic acid,

00:34:12 lactate had that

00:34:13 and they were using lactate.

00:34:15 Now if a youngster cannot handle his own lactate,

00:34:18 how could he burn up the lactate

00:34:20 that was in the sodium lactate?

00:34:22 It was a waste of time

00:34:23 and I'll demonstrate that soon.

00:34:24 May I have the next slide please?

00:34:26 And why was lactate given?

00:34:28 Sodium lactate was given in acidosis

00:34:31 on a theory that the lactate would be metabolized

00:34:34 or excreted

00:34:35 and the sodium would be utilized

00:34:37 and there's a famous solution.

00:34:39 What's the name of it?

00:34:41 Those of you who are interested.

00:34:43 Lactate ringers.

00:34:45 No, there's a man's name attached to it.

00:34:47 Ringers.

00:34:48 Ringers Lactate.

00:34:49 Yeah, Ringers Lactate.

00:34:50 He was the one who introduced lactate

00:34:52 to correct alcohol.

00:34:53 You see, it didn't have to do anything.

00:34:55 Everything they did

00:34:57 was not to do anything.

00:34:58 For example,

00:34:59 leave the child alone for 48 hours.

00:35:01 Well, you don't have a problem.

00:35:03 You don't have anything to do.

00:35:05 Use Ringers Lactate

00:35:07 to correct the alcohol.

00:35:08 Then you don't have to worry about too much.

00:35:12 This is a ray bug you read.

00:35:14 I doubt whether a lot of you are young

00:35:16 or people have seen this.

00:35:17 You just turn this

00:35:18 and mercury comes out

00:35:19 and pushes the stuff out.

00:35:21 This is where we did chloride.

00:35:23 We used to titrate the chloride.

00:35:25 You can do a chloride

00:35:26 within a half a percent this way.

00:35:29 You can do it better

00:35:30 with amperometric titration

00:35:32 but when you start going to colorimetric methods

00:35:34 in the autoanalyzer,

00:35:36 you're plus or minus 10%.

00:35:38 May I have the next slide, please?

00:35:41 Now, this was a chart of a youngster.

00:35:46 Remember, this is why the adrenal immaturity

00:35:49 does not mean that I know

00:35:50 that the adrenal is at fault.

00:35:52 The child loses salt.

00:35:54 But I'm not focusing on salt.

00:35:56 I'm focusing on the hematocrit.

00:36:01 You notice the hematocrit is high.

00:36:04 There was only one hematocrit

00:36:06 reported in the literature

00:36:07 when I started this work.

00:36:08 There was a very low one of a child

00:36:10 that was about six months old.

00:36:12 No one knew that premature

00:36:15 and newborns had very high hematocrit.

00:36:17 Around 60 is normal for a newborn baby.

00:36:20 May I have the next slide?

00:36:23 Another way to measure that.

00:36:25 Now, the first thing I did was I said,

00:36:27 I'm going to do exactly what they say.

00:36:29 Here's a child that weighed 800 grams,

00:36:32 754 grams.

00:36:34 That meant that 99 out of 100 would die.

00:36:37 That's what it meant.

00:36:38 That's what it meant.

00:36:39 It was a death sentence.

00:36:41 Dr. Crawford at Rockford said,

00:36:43 they don't even have this kid.

00:36:44 It's garbage.

00:36:45 It's not going to survive.

00:36:47 I said, okay.

00:36:48 I put it on a scale.

00:36:51 Periodically, I took the reading

00:36:53 and took part of the weight.

00:36:55 I found that in 24 hours,

00:36:57 and I was supposed to leave her alone

00:36:59 for 72 hours according to the directions

00:37:01 in Clement Smith's book,

00:37:04 and it had lost,

00:37:06 give or take six or ten grams of death.

00:37:08 It died at the end of 24 hours,

00:37:11 and it lost 20% of its body weight.

00:37:15 May I have the next slide, please?

00:37:20 I said, therefore,

00:37:22 we've got the secret of how to manage a premature.

00:37:25 Just keep them hydrated.

00:37:27 And how do you keep them hydrated?

00:37:29 The way you do it with adults.

00:37:31 Well, let's see what we did here.

00:37:33 Well, this is Louis Cacciatore.

00:37:35 Louis Cacciatore is a butcher in Rockford, Illinois.

00:37:39 He's still alive.

00:37:40 He's about 40 years old now.

00:37:42 When I'm going to Chicago in the fall,

00:37:45 I'll step by because he always invites me

00:37:47 to his steak dinner.

00:37:48 Now, first of all, I have to get the fluids in.

00:37:53 I'm a chemist.

00:37:54 I know nothing about how to handle a premature.

00:37:56 So I figured the best way to do it

00:37:59 is to do what they do in Cincinnati.

00:38:02 You may not know it,

00:38:03 but there's a reference to two doctors here in Cincinnati

00:38:06 who work with the polyethylene tube.

00:38:08 Do you know who they are?

00:38:10 Go put the lights on.

00:38:13 I want to ask if anybody knows these doctors.

00:38:16 They're still alive.

00:38:17 I'd like to talk to them.

00:38:19 Could you find a picture of someone,

00:38:31 a baby with a polyethylene tube?

00:38:33 I don't think there's an end date.

00:38:37 Down below, it'll give you the name of two Cincinnati doctors.

00:38:44 Here they are.

00:38:46 Here's a polyethylene tube and some of the babies.

00:38:49 And now let's look at the previous page.

00:38:55 Credit should be given to Dr. Daniel V. Jones

00:38:59 and E. Wagner of the Cincinnati General Hospital

00:39:01 for their outstanding work.

00:39:05 Credit should be given to Dr. Daniel V. Jones

00:39:10 and E. Wagner of the Cincinnati General Hospital

00:39:13 for stimulating the use of indwelling polyethylene tubes.

00:39:16 Does anybody know these two doctors?

00:39:19 That was 40 years ago.

00:39:21 Assuming they were 30 then, they'd be about 70 now,

00:39:24 and they probably were more than 30 then.

00:39:26 But anyway, I didn't invent the polyethylene tube,

00:39:30 but I used it on prematures, which no one had ever done.

00:39:32 Put the new light on.

00:39:36 So I put a polyethylene tube in,

00:39:38 and at 8 hours, arbitrarily, I said,

00:39:40 I'm not going to wait 24 hours.

00:39:42 I'm going to start giving this youngster food at 8 hours.

00:39:45 So let's see.

00:39:46 This is the paradigm of the whole treatment.

00:39:50 I gave 10 million salers, 23 million ladies,

00:39:53 and 5% of them were washing water

00:39:55 through a polyethylene tube.

00:39:57 Now look at this.

00:39:58 The stomach capacity of that infant

00:40:01 was 4 cc.

00:40:03 You know what 4 cc is?

00:40:05 The FTE time was 3 cc.

00:40:09 So that, how much could you get in?

00:40:11 3 cc per hour times 24 hours,

00:40:14 about 70-some-odd cc.

00:40:16 He needed about 150.

00:40:18 So I set up a crisis.

00:40:22 What's a crisis?

00:40:24 Where does it say crisis?

00:40:25 Right there.

00:40:26 Where your pointer is.

00:40:27 Crisis.

00:40:28 About 15 days.

00:40:30 There's a crisis up here, too.

00:40:32 A crisis, right.

00:40:33 A crisis.

00:40:34 10 million a saler was 23 million.

00:40:37 And to my amazement, the crisis went in.

00:40:39 This was absorbed like in a dry sponge.

00:40:42 And at this, 15 days, so on.

00:40:47 Meanwhile, I wasn't doing any chemistries on him

00:40:49 because I was busy trying to take care of this father.

00:40:53 By this time, when he got into trouble,

00:40:56 I was sitting in my office,

00:40:58 and his father came in and wanted to take the body.

00:41:01 Of course, they had called him

00:41:02 and told him the baby wasn't breathing.

00:41:05 But I had an anesthesiologist who pumped him,

00:41:09 and I said, no, we don't give up.

00:41:11 And I got a sample of blood, and here's what I found.

00:41:15 115 chloride, 137 sodium.

00:41:18 What does that mean?

00:41:19 It's an acidosis.

00:41:21 So we gave him a little bicarbonate.

00:41:24 The urea was 33, and he was drying out.

00:41:28 So we increased everything,

00:41:30 and now I started pumping breast milk.

00:41:33 The reason I got breast milk

00:41:35 is because his mother started to pour breast milk,

00:41:37 and it was available.

00:41:38 Up to then, I couldn't get it.

00:41:40 I had to borrow it from some other people.

00:41:42 Anyway, we started using breast milk,

00:41:44 and what we did was put salt in the breast milk

00:41:48 to try to hold it.

00:41:50 120 sodium, 85 chloride.

00:41:53 We kept giving him salt in his breast milk.

00:41:56 It kept dropping off.

00:41:58 Therefore, we came to the conclusion

00:42:00 that there was a salt-losing phenomenon in these kids,

00:42:03 that they didn't have a mature adrenal system.

00:42:08 In other words, what I was saying is

00:42:10 they don't produce alpha-serone.

00:42:13 This went on until I'll show you.

00:42:17 I made a very interesting discovery at this point here.

00:42:21 We gave 5 milliliters of blood.

00:42:23 Now, the reason we gave 5 milliliters of blood

00:42:26 was we saw this dropping hematically.

00:42:28 I didn't know whether 41 was good or bad for premature.

00:42:32 But I didn't see any premature.

00:42:34 So I said, let's give him 5.

00:42:36 As soon as we gave him 5 milliliters of blood,

00:42:38 and then we saw a sharp rise in chloride.

00:42:43 Now, let's see.

00:42:45 Let me have the next slide, please.

00:42:52 Finally, we kept on giving blood

00:42:54 because he seemed to look better.

00:42:56 And there was a sharp rise.

00:42:58 Notice the chloride here and the chloride up here.

00:43:02 Now, we didn't give him any more salt.

00:43:04 We concluded there was a hormone in the blood

00:43:07 which was holding the salt.

00:43:09 And that's when we started giving him

00:43:11 desoxychortical serone by mouth.

00:43:14 In other words, by the time he was 61 days,

00:43:18 we moved the polyethylene to him.

00:43:20 We had a good supple reflex.

00:43:22 And we gave him orally, in other words,

00:43:24 we took the breast milk, added a gram of salt,

00:43:28 mixed it up, and then fed it to him.

00:43:30 He was getting about 150 to 200 cc of breast milk a day

00:43:35 and desoxychortical serone.

00:43:37 Finally, desoxychortical serone was discontinued.

00:43:40 And we sent him home.

00:43:42 Ten months later, he was perfectly normal.

00:43:45 And then we realized we had made a discovery

00:43:49 because we found this to be true in every low-weight premature.

00:43:53 The secret to maintaining a low-weight premature

00:43:55 was to give him two things, salt and hormone support.

00:43:58 And the best way to give him hormone support

00:44:00 was to give him a little blood.

00:44:02 But if you didn't, it was not very effective.

00:44:05 But we didn't know all of the serone at that time.

00:44:07 Today, I imagine there's some.

00:44:09 I was hoping Tsang would be here to find out

00:44:11 if they give all of the serone.

00:44:13 May I have the next slide, please?

00:44:16 This is what he looked at at birth.

00:44:18 Over here is my hand.

00:44:20 My hand was bigger.

00:44:22 It was the whole length from here to here.

00:44:24 In other words, he was about this length.

00:44:27 That's how big he was.

00:44:29 And this is what he looked like

00:44:33 at a 1 pound 9 ounce at birth

00:44:36 at that one year.

00:44:39 That's not the same patient.

00:44:41 It's another patient.

00:44:43 It's the same ID.

00:44:45 May I have the next slide, please?

00:44:49 That caused an explosion in the United States.

00:44:52 A meeting was held...

00:44:54 Can you put the lights on, please?

00:44:56 I better get on because this is taking longer than I thought.

00:45:00 I'll be finished in about five minutes.

00:45:04 What do you need?

00:45:06 A meeting was held

00:45:08 of the leading pediatricians in the country,

00:45:11 and they had a symposium in the corner of New York

00:45:13 and New York Pediatrics,

00:45:15 each one saying vile things,

00:45:17 saying that the salt is the hoisting for prematures.

00:45:20 They were led by Clement Smith

00:45:23 and also by a guy I never worked for,

00:45:25 and also by Charles Levine.

00:45:27 And they ripped me apart.

00:45:29 And this is the answer to it later on

00:45:32 that I gave at that time.

00:45:36 I have here the name of 12 of the institutions.

00:45:39 You name a famous institution,

00:45:41 there was somebody there writing a criticism.

00:45:44 The criticism all through was,

00:45:46 if you give salt, they'll get retrolateral fibroblast.

00:45:49 Of course, retrolateral fibroblast has nothing.

00:45:51 This afternoon, this evening,

00:45:53 I'm going to put up the statements they made,

00:45:56 and I'm not putting their names down

00:45:58 because they'd be ashamed of it if they were here.

00:46:00 May I put the lights out now?

00:46:05 I just picked one here.

00:46:07 The authors present such data finding in many instances

00:46:09 low sodium chloride levels,

00:46:11 elevated fasting, extreme acidosis.

00:46:13 Methods employed use fingerprick blood.

00:46:16 Since these authors are much more intimately familiar than I with them,

00:46:19 they gave me a lot of the microtechniques.

00:46:22 They were one to send a sudden hesitation

00:46:24 to accept their usual findings that they confirmed elsewhere.

00:46:27 I said to myself, déjà vu.

00:46:29 That's what they wrote about Benjamin's

00:46:31 Kramer-Tisdale micro-method for calcium.

00:46:35 May I have the next slide, please?

00:46:40 For the next 20 years,

00:46:43 papers from Mayo Clinic,

00:46:46 from Clemens Smith's laboratory,

00:46:48 from Hopkins came out,

00:46:50 and everyone said the same thing.

00:46:52 It's remarkable the way prematures

00:46:55 are able to tolerate salt

00:46:58 and how they lose it so easily.

00:47:01 But nobody referred to Nielsen.

00:47:04 This is a summary in Pediatric Colleges of February 1979.

00:47:08 These data suggest that the daily sodium requirement

00:47:11 of immature sick infants,

00:47:13 and Nielsen uses the word I used,

00:47:15 immature instead of premature,

00:47:17 may be much higher than was previously thought.

00:47:20 In such infants, the investigators say

00:47:22 urinary sodium should be monitored

00:47:24 and sodium intake adjusted to prevent

00:47:26 hyponatremia in the first place.

00:47:29 And they refer to this paper in the Journal of the End.

00:47:32 I said that in 1951,

00:47:35 and this is 1979.

00:47:37 In the interim, there were at least 20 or 30 papers.

00:47:40 Not one of them referred to the original work

00:47:43 which we have done.

00:47:45 May I have the next slide, please?

00:47:48 Now, I didn't ignore the outcome methodology.

00:47:53 I kept looking for a convenient way

00:47:56 of doing what everybody wants.

00:47:58 Some method we put the blood in and press the button.

00:48:00 And I developed this tape system,

00:48:02 I call it an analysis,

00:48:04 which is now called the Kodak ectochrome system.

00:48:07 And this is my patent, which says,

00:48:10 and I want to read it so that you'll understand,

00:48:12 an arrangement of chemical analysis

00:48:14 comprising the combination

00:48:16 of three flat strips,

00:48:18 medium, superimposed one on the other,

00:48:20 the outer medium on the one side being absorbent

00:48:23 and designed to receive a sample,

00:48:25 the intermediate medium being non-reactive,

00:48:28 porous and of pore size,

00:48:30 such that it's bindled to water, but molecules in it

00:48:32 that are molecular weight higher than proteins

00:48:34 cannot pass their proof.

00:48:36 The outer medium on the other side being a test tube

00:48:39 which is sampled from the paper.

00:48:41 Obviously, the diesel Kodak system

00:48:45 violates that patent.

00:48:47 But, in 1980,

00:48:49 I was looking at the ectochrome system,

00:48:51 and I didn't have my name on here,

00:48:53 and I said to the kid who was there,

00:48:56 you know, he said,

00:48:58 where can we buy this machine?

00:49:01 And he said, well, we're waiting for Nagelson's patents to expire.

00:49:04 And that is the ectochrome system.

00:49:06 May I have the next slide, please?

00:49:10 And here, I propose that it be used in space.

00:49:13 And I went down to NASA to demonstrate it.

00:49:15 Contracts have now proposed a biological solution

00:49:18 to the gravity-free environment

00:49:20 using that tape system.

00:49:21 May I have the next slide, please?

00:49:23 They said, at least the objectives

00:49:26 are receiving tape,

00:49:28 a porous tape,

00:49:30 and reagent tape.

00:49:31 May I have the next slide?

00:49:34 And this shows that this is by reflection,

00:49:37 and this is by transmission,

00:49:39 showing that reflection.

00:49:40 All of these things were available to Eastman,

00:49:43 and they had the advantage of being able to use it.

00:49:46 May I have the final slide?

00:49:48 This is the machine that I delivered to them.

00:49:51 This is schematic.

00:49:53 The specimen is put here, 10 microliters,

00:49:55 goes around,

00:49:57 this is a piece of cellophane,

00:49:58 this is reagent tape,

00:50:00 comes out here,

00:50:01 they're separated here,

00:50:03 and this goes on to the core.

00:50:06 Today, it's a little card.

00:50:08 Do you have the instrument here?

00:50:10 Dr. Pesci, do you have an Eastman core?

00:50:12 No, no, we don't have that.

00:50:14 We have it at the VA.

00:50:15 What?

00:50:16 At the VA, Veterans Hospital has it.

00:50:18 Well, it's now the fastest-growing system.

00:50:22 Whitehead of Technicon, at the time that I showed this,

00:50:25 said to me,

00:50:26 I'm not afraid of any of these other systems,

00:50:28 but if this thing ever goes on the market,

00:50:30 we close shop.

00:50:32 And it's true, they're closing shop.

00:50:34 As a matter of fact, you can't buy a Technicon anymore.

00:50:36 May I have the next slide?

00:50:39 And this is what the machine looked like.

00:50:41 It was built large because it, after all, was homemade,

00:50:45 and the specimen comes in.

00:50:47 This is the tape that's going to receive the specimen.

00:50:50 This is a complicated machine

00:50:52 where you put the specimen in the capillary,

00:50:54 and the capillary dumps it on.

00:50:56 I was too complicated.

00:50:57 But finally, here, it goes through this heater,

00:51:00 and it's red, and it's red in the colorimeter,

00:51:03 and I had to develop a colorimeter.

00:51:06 And don't forget, I didn't have the modern system.

00:51:10 But this entire machine was hand-built by you.

00:51:12 Pardon me?

00:51:13 You said this entire instrument was hand-built by you.

00:51:16 That's right.

00:51:17 May I have the next slide?

00:51:20 This is Easton's patent, Easton Kodak.

00:51:25 And let's read what they say in their patent.

00:51:27 They finally got a patent, too.

00:51:30 Mine is in 1961, and theirs is 1976.

00:51:35 An integral element for analysis of liquid,

00:51:37 set element of colliding fluid content,

00:51:39 an isotropically porous spreading layer.

00:51:42 That's the paper.

00:51:44 Colliding a non-fibrous material.

00:51:46 This is the invention.

00:51:48 They said you could do it without paper.

00:51:50 Incidentally, what they're using is paper.

00:51:54 And the reagent layer permeable to a substance spreadable

00:51:57 within the spreading layer, or reaction process.

00:52:00 So they got a, what you call a dependent patent,

00:52:04 saying that they could do it without using paper

00:52:07 on the receiving end.

00:52:09 And they finally could.

00:52:10 But they introduced one layer that was very good.

00:52:12 They introduced titanium dioxide,

00:52:14 which is a better reflector.

00:52:16 Excuse me.

00:52:17 May I have the next, may I have the lights, please?

00:52:20 So it's all lit up.

00:52:21 Again, I will say this.

00:52:23 Prematures of full-term infants are now monitored

00:52:26 as signs of dehydration.

00:52:28 And just go up to the pediatric floor.

00:52:30 And one of the people who reviewed in this criticism

00:52:34 said that I would hate to see every kid

00:52:36 with a polyethylene tube in his nose.

00:52:38 Well, I can tell you this.

00:52:39 Every kid in your premature center

00:52:43 has a polyethylene tube in his nose.

00:52:46 As a result of our production in mortality statistics,

00:52:50 and I just pointed out the fact that this

00:52:52 was of greater benefit.

00:52:54 I don't know of any invention, including penicillin,

00:52:58 that had a greater impact on the mortality statistics than this.

00:53:02 Milk formulas are now designed to simulate

00:53:04 the composition of breast milk.

00:53:06 And starch hydrolysis have completely replaced lactose.

00:53:09 Calcium administration is now carried out

00:53:11 exclusively with chelated calcium.

00:53:13 So these were the contributions that I made at that time.

00:53:17 Put the light on.

00:53:19 Now, I made this paper specifically for himself,

00:53:24 for his benefit.

00:53:25 You know why?

00:53:26 Because when I asked him if he knew what I had done

00:53:28 in pediatrics, he didn't know.

00:53:29 He knew that I had made a microgasometer.

00:53:32 He knew that I had developed methodology.

00:53:34 But he didn't realize that the clinical chemist

00:53:36 was not interested in the methodology.

00:53:38 He was interested in using it.

00:53:41 And that was what Liebig and Verla.

00:53:44 Liebig was a clinical chemist, and he was studying urine,

00:53:47 and he synthesized urea.

00:53:49 Verla was the M&E.

00:53:51 And Louis Pasteur was a clinical chemist.

00:53:55 Berzelius was a clinical chemist.

00:53:57 He used the word organic chemist,

00:53:59 and he was responsible for isolating uric acid from urine,

00:54:05 and so on.

00:54:07 So the profession of clinical chemistry

00:54:10 has been an honored profession

00:54:12 since the days when the word chemistry was invented.

00:54:15 Chemistry was invented by clinical chemists.

00:54:18 The clinical chemists were the people

00:54:20 who were able to take silver and make it black with sulfur.

00:54:26 And that's what the word chemist means,

00:54:28 the blackeners, the people who make things black.

00:54:30 And therefore, if you could take silver and make it black,

00:54:33 obviously you could cure disease.

00:54:36 Once again, the alchemist used to say,

00:54:44 the purpose of alchemy is not to make anyone rich

00:54:49 but to cure disease.

00:54:51 And we have to find cures for disease.

00:54:53 Von Hellman was a clinical chemist

00:54:56 who invented the balance that was used for many, many years,

00:54:59 the gravity balance.

00:55:01 And he was also a clinical chemist.

00:55:03 He called himself an iacrochemist.

00:55:06 The word iacro means medicine.

00:55:09 So the clinical chemist was called an organic chemist,

00:55:12 an iacrochemist, a biochemist.

00:55:15 When the biochemists first formed a society,

00:55:17 there was clinical chemistry.

00:55:19 The early years of the general and biological chemistry

00:55:21 were all clinical chemistry.

00:55:23 But today we have a new class of clinical chemists,

00:55:26 the analytical clinical chemists,

00:55:28 who have replaced,

00:55:30 and it has nothing to do with the physician.

00:55:33 He's not, doesn't cooperate with him.

00:55:36 The clinical chemistry lab used to be the center of the hospital,

00:55:39 and all the research that went on in that hospital.

00:55:41 I remember what was true in every single hospital.

00:55:45 Thank you.

00:55:50 Incidentally, one thing I would like to point out.

00:55:53 These methods were spread all over the world.

00:55:57 Abbott wrote them up here,

00:55:59 and he wrote them up here in what's new.

00:56:02 Then they wrote it up in a mosque on medicine, a Spanish thing.

00:56:07 Take a look at this.

00:56:09 And here's one in Italian.

00:56:11 And this is in the 60s in Abbott's magazine.

00:56:16 These methodologies.

00:56:18 But they all featured the methodology, not what was done.

00:56:21 Very interesting.

00:56:23 Thank you.

00:56:30 They were made in 1951 or so.

00:56:34 And the visibility is not very good.

00:56:37 It's small.

00:56:39 And the way the audience is disposed is going to be very difficult to see that

00:56:43 unless you have a telescopic vision.

00:56:46 So I'll read this.

00:56:48 It says, Outcome of Nielsen's Pediatric Studies.

00:56:52 Prematures and full-time infants are now monitored by signs of dehydration.

00:56:57 Okay, are we on?

00:56:59 More signs of dehydration.

00:57:02 Especially in a matter like pH of blood pressure on a routine basis.

00:57:06 I went up to the third floor where there was a neonatal intensive care unit.

00:57:15 I'm the grandfather of that unit, you might say,

00:57:19 because prior to my activities in this field, there was no such thing.

00:57:25 The result of one of our remarkable reduction of mortality rates has resulted.

00:57:29 People don't realize that in 1951,

00:57:32 a baby was born weighing about four pounds

00:57:35 and only had one in two chances of survival.

00:57:38 It would weigh less than 1,000 grams.

00:57:41 It had no chance of survival.

00:57:45 Milk formulas are now designed to simulate the composition of breast milk,

00:57:51 1% protein.

00:57:54 The reason I put that up there was because

00:57:57 a pediatrician by the name of Charles Levine from Hopkins

00:58:02 had written a paper in which he advocated high-protein milks.

00:58:07 In working on a pediatric floor, and I'll tell you about that,

00:58:12 I noticed that these children became severely acidotic on high-protein milks

00:58:18 and had very high ureas, as you would expect.

00:58:21 So I did studies comparing breast milk versus high-protein milks

00:58:28 and showed that the high-protein milks were a disaster.

00:58:31 As a result, if you go and look around,

00:58:34 you'll see the advertisements for things like Infamilk,

00:58:37 which are milks which imitate human breast milk.

00:58:45 Starch hydrolysis has completely replaced lactose as a source of calories.

00:58:49 I was given the job to find out why lactose was such a horrible thing to put into a formula.

00:58:55 Children had foul-smelling stools and would not survive, do very well.

00:59:03 When I examined the stools, I found that the lactose that had gone in and came right out unchanged.

00:59:09 Most of it, some of it came out in the urine.

00:59:11 None of it, or very little of it, was changed to galactose glucose.

00:59:18 Which was quite surprising.

00:59:20 And therefore, lactose was no good for infants.

00:59:25 And then, of course, lactose is milk sugar. That didn't make any sense.

00:59:29 I'll show you what the problem was.

00:59:31 Calcium administration is now carried out exclusively with chelated calcium columns,

00:59:35 especially with hexose phosphate.

00:59:37 When I came into this field in the 30s, the major problem in pediatrics was records.

00:59:44 I told this morning group that I had two older brothers, twins, both of whom died of the English disease.

00:59:50 The English bronchitis, or the English disease, was Ricketts.

00:59:54 And all over Europe, all over England, all over the United States,

00:59:58 the floor at the Brooklyn Jewish Hospital had 70 children with Ricketts at the same time.

01:00:05 There was no vitamin D milk.

01:00:07 And even with cod liver oil, it didn't work on all children.

01:00:13 I was given the job of finding a way of getting calcium into these children.

01:00:17 There was a gentleman who ran an epileptic clinic.

01:00:21 Ninety percent of the patients ran calcium with a Y.

01:00:25 They were children who had hypocalcemia.

01:00:29 May I have the next slide, please?

01:00:33 And at that time, I don't see this slide here.

01:00:40 If you turn the page on this chart, you'll see what happened.

01:00:46 There are three slides that I'm not showing, apparently.

01:00:50 These three slides show that calcium fructose diphosphate, calcium phosphate was not absorbed.

01:00:56 Calcium carbonate was not absorbed.

01:00:58 Calcium citrate was not absorbed.

01:01:00 We tried everything.

01:01:01 And finally, I found calcium fructose diphosphate was absorbed quantitatively

01:01:06 and could cure Ricketts without any vitamin D.

01:01:09 And that was an interesting thing.

01:01:11 And Dr. Benjamin Kramer, at that time, who was head of the pediatric department, said,

01:01:16 Nelson, you'd have gotten your name in headlines if not for the discovery of vitamin D.

01:01:22 Because we had a cure for Ricketts, but it was useless.

01:01:26 People were using cod liver oil instead.

01:01:28 Now, if you used cod liver oil with milk, you were just as well off.

01:01:32 But basically, what I showed was that calcium could not be absorbed very well unless it was chelated with a hexose phosphate.

01:01:40 And that's essentially what it is in milk.

01:01:46 Now, at that time, when I came to Rockford in 1949,

01:01:57 I had had 16 years of experience working and doing research in pediatrics.

01:02:03 I had developed a galaxy of micro-methods because I was originally trained as a micro-analyst.

01:02:11 And I was given certain problems.

01:02:15 One of the problems was what are we going to do about this mortality statistics with premature births.

01:02:24 Could I borrow one of those books, please?

01:02:27 Those green ones are green books.

01:02:39 These are the kind of things you'll read in here.

01:02:42 Bunderson, who was made the Surgeon General of the United States at that time,

01:02:48 said the mortality statistics on neonates, and particularly premature births, is a disgrace in the United States.

01:02:58 If a child weighed 4 pounds, which is a pretty big infant, it only had a 50% chance of survival.

01:03:07 If it weighed 1,000 grams or less, it had less than one chance in 20 of survival.

01:03:15 Now, I knew certain facts before I came to Rockford.

01:03:22 I knew there was such a thing as immaturity.

01:03:26 And the way I knew that was because of the fact that working with calcium,

01:03:33 there were some children who were born and would have low calciums.

01:03:37 You would give them calcium, and I used calcium fructose diphosphate,

01:03:41 and give them AT10, which is a relative of vitamin D,

01:03:45 and which was available long before vitamin D was available, and was made from a gospel.

01:03:51 And their calcium would come up.

01:03:54 You'd stop the treatment and down it, drop to 5.

01:03:58 You would then repeat the treatment.

01:04:00 And you went this up and down for about a week, two weeks, sometimes three weeks, sometimes once a month,

01:04:06 when suddenly, one morning, you'd come in and the youngster had a calcium of 10, and it stayed there.

01:04:12 And you didn't have to give them any more treatment.

01:04:15 So Dr. Katus, who was head of these children, said,

01:04:19 this shows that their calcium balance, their parathormone,

01:04:25 of course, they didn't know anything about calcitonin, their system is inadequate, ineffective,

01:04:31 and that they're immature in the sense that it hasn't matured.

01:04:34 Now that it's matured, they have grown out of it.

01:04:36 You know that expression? Grown out of it means matured.

01:04:40 Now, I say here, certain infants are born with an inherent inability to respond with normal growth and development,

01:04:51 and conditions of treatment under which the vast majority of infants flourish.

01:04:56 The smaller infant is at a disadvantage, and the point here is they tend to become dehydrated most easily.

01:05:03 For this reason, the smallest infant is an acute and urgent problem in fluid therapy.

01:05:10 Now, in the purpose of this report, to which this is out of focus,

01:05:19 we discussed, illustrated the cases of the various findings common to the immature, which can be successfully treated.

01:05:26 Now, there was another type of immaturity that was very common among premature.

01:05:30 They would be born prematurely born with high hematocrits.

01:05:33 And then you would, and there could be a big one, a 1,500 gram one or so, a 2,000 gram one,

01:05:41 and you'd notice if you measured the hematocrit dropping steadily over a period of maybe a month, two months,

01:05:47 so you'd give them hematinics, you would give them iron, B12, everything that you could think of, including folic acid,

01:05:56 and they would not respond, nothing.

01:05:58 But if you gave them blood, that was fine.

01:06:00 You could raise the hematocrit.

01:06:02 And then you came back two weeks later, and they were back to a hematocrit of 20.

01:06:07 We'd give them some blood and kick them up to 40 or 45, and then two weeks later, they were down to 20.

01:06:13 All of a sudden, one day, the mother would bring them in, and the hematocrit had stayed up.

01:06:17 Their reticular endothelial system had matured, and they didn't need any more treatment.

01:06:23 So I knew that there were many systems in the body which were not mature at birth,

01:06:29 and I was not surprised to find that the system which controls sodium and fluoride balance in the body could be immature,

01:06:39 and not only that, but that it was immature in every low-weight premature infant.

01:06:44 That was a remarkable discovery that we made at that time.

01:06:48 May I have the next slide, please?

01:06:53 Oh, this is a big one, 1398 grams.

01:06:57 And what does this show?

01:06:59 Oh, this shows—he's got the top chopped off.

01:07:02 This shows one of those children with an immature reticular endothelial system.

01:07:09 There were some physicians who would not go along with us, and therefore, I used their patients as controllers.

01:07:17 The child starts out at 58, and at 41 days, it's down to 25.

01:07:24 At 110 days, it's 128, and it's now an idiot.

01:07:28 The child now falls way below normal, because nowhere—

01:07:33 Now, this child was given every hematinic that you could think of, repeatedly, and no response.

01:07:41 In other words, this child had an immature reticular endothelial system.

01:07:45 Had he been given blood earlier, I believe he would have been able to mature.

01:07:50 Maybe every time we gave him blood, we gave him similar to a poet, and I don't know.

01:07:54 But one thing is clear, that this child was mistreated in the sense that he didn't—

01:08:00 the pediatrician did not recognize that he had an immature infant,

01:08:04 immature in the sense that he didn't have a mature reticular endothelial system.

01:08:09 May I have the next slide, please?

01:08:12 This is another child who had the same problem, but had one difference.

01:08:16 This child got repeated transfusions all the way through.

01:08:21 At the end of 59 days—

01:08:26 Notice here, he's not being treated.

01:08:29 At the end of 53 days, his hematomas had taken flight, and it seems to stay up.

01:08:38 He went on, and we left him alone, and he was discharged,

01:08:42 because for about, oh, 10 or 15 days in a row, there was no droplet of hematoma.

01:08:48 But all along, he had gotten slight shots of blood, 5 cc, 10 cc, 15 cc,

01:08:57 so that we recommended that blood be given at the end.

01:09:01 This was a heresy.

01:09:03 Under no circumstance should you ever give blood to a newborn infant.

01:09:06 That was the feeling at that time.

01:09:08 There was too much danger of hepatitis, but there was no choice.

01:09:12 You either ended up with an idiot, or you gave him blood.

01:09:15 May I have the next slide, please?

01:09:25 One of the interesting things was this.

01:09:27 I was one of the few people in the country who had a pH meter that worked on small quantities.

01:09:34 This child was on high-protein milks, and as expected, on schedule, the pH dropped down to 7.1.

01:09:46 At this point, there are little numbers here to show me what happened.

01:09:51 At this point, notice over here, his total CO2 is down to 1, and 7 over here, pH 7.1.

01:10:00 At this point, we gave the child sodium lactate as my solution.

01:10:06 Now, sodium lactate is an acid solution.

01:10:09 It has excess lactic acid added as a reservative, and the pH is around 6,

01:10:17 so that this child was not able to metabolize the lactic acid.

01:10:22 As a result, his pH got even lower.

01:10:25 Sodium lactate is not an alkalizing solution for a child in severe acidity.

01:10:31 Now, everybody was afraid of sodium bicarbonate.

01:10:34 They were afraid that you'd over-treat them easily, and sodium bicarbonate was a little better.

01:10:39 Therefore, I had a pH meter, and I didn't have to worry about that, so I hydrated these kids,

01:10:45 and here we get sodium bicarbonate. I bring it up to 7.21.

01:10:49 That goes back on that same milk, and the pH drops to 7.1.

01:10:53 Then, of course, I keep giving him sodium bicarbonate, bring it to 7.2, and then he goes on.

01:11:01 He can even handle a high-protein milk.

01:11:04 May I have the next slide, please?

01:11:10 This is what happens to the growth rate of a child.

01:11:13 When you bring them out of the acid pH, of course, to normal pH, you just take the slide off.

01:11:18 May I have the next slide?

01:11:35 Oh, show that slide. That's important.

01:11:44 In order to give fluids, you understand that I'm not a physician,

01:11:50 and I have to find an easy way of giving fluids.

01:11:53 I didn't know. I was not skilled in cutting down on a scalpel blade or anything like that.

01:11:58 So, here in Cincinnati, by Dr. Jones, and what's the other fellow's name I forgot?

01:12:04 Two pediatricians had started using polyethylene tubes in newborns,

01:12:11 so I used a finer one, about one-fifth what they used, and put it down this infant's stomach.

01:12:18 I measured the infant's stomach, and I'll show you how small they were,

01:12:22 and started giving fluids through the nose.

01:12:25 Why bother giving sodium bicarbonate solution through a vein, or if you can give it by mouth?

01:12:32 As a matter of fact, the use of bicarbonate rectally and orally

01:12:38 was very common at the turn of the century.

01:12:42 It was a standard form of treatment, because then you didn't have to worry about over-treatment.

01:12:47 On the other hand, when they started using sodium bicarbonate for medicine,

01:12:50 they started killing children with alkalosis, because if you follow the titration curve,

01:12:55 if you give just a little bit too much, the pH just jumps up to about one.

01:13:00 So, if you walk on the third floor, you'll find all the kids,

01:13:05 every one of them has one of these tubes in his nose,

01:13:08 and they have all kinds of equipment on them, and that's important,

01:13:11 because I'm going to tell you about that in a few minutes, why that's important.

01:13:15 And the next slide.

01:13:17 Now, the first thing I found was that if you give these kids salt, they lose it.

01:13:24 You start out with chloride of, let's say, 80, and you say,

01:13:28 I'm going to add 250 milligrams of salt to their formula,

01:13:34 and that should raise the sodium chloride level.

01:13:36 You calculate out how much you give them.

01:13:38 You have to calculate it out, because it's a very small volume you're dealing with.

01:13:43 And you give them the salt, and it goes up for a short time,

01:13:48 and then the next thing you know, the next morning, the salt's gone.

01:13:51 You find it all in the urine.

01:13:53 So that this happened repeatedly, particularly in the very small brigature.

01:13:58 They were very hard to keep hydrated.

01:14:02 So I came to the conclusion that they were suffering from immaturity of the adrenal system.

01:14:12 In other words, they didn't have the necessary salt-mutating hormones.

01:14:18 I put it in quotation marks, and I say down here,

01:14:22 the term adrenal immaturity is used here to don't designate a condition

01:14:27 resulting in the inability of the infant to hold water, sodium, iron, and chloride,

01:14:33 in the face of the administration of these substances in what would be more than adequate

01:14:39 for a normal infant of equal weight.

01:14:42 There was no unequivocal histological or pathological evidence to support the thesis

01:14:49 that the adrenal is involved.

01:14:51 That statement is not true, because subsequent to this,

01:14:55 we did get autopsy reports, and their adrenal was involved.

01:14:59 We showed some children had adrenals that were something like one-tenth the normal weight

01:15:04 of the other children.

01:15:05 And I have the next slide.

01:15:08 So I decided to do an experiment.

01:15:12 The books which came out of Harvard and Yale and places like that and Hopkins,

01:15:17 there were books called The Premature, and it said,

01:15:21 if a child weighs less than 1,000 grams, leave him alone for 72 hours.

01:15:26 If he weighs less than 2,000 grams, then leave him alone for 24 hours.

01:15:31 So I took a child who was born, a white female, who weighed 754 grams,

01:15:39 and I said, let's follow this procedure.

01:15:41 Only one difference.

01:15:42 I put him on a scale, and every hour or so I took the weight.

01:15:47 At the end of 24 hours, the kid was dead, and he had lost 20% of his body weight.

01:15:53 Therefore, what did that tell me?

01:15:55 That told me that you had to hydrate the child.

01:15:59 You had to somehow or other find some way of getting fluids in him.

01:16:02 The only way I knew was to use crisis, you know, just stick a needle in the butt,

01:16:07 and the other was through the polyethylene tube, and I used both.

01:16:11 I have the next slide.

01:16:14 Here I'm showing a paradigm of this technique, how I went about it.

01:16:20 This was the first one that I took for 80 days, and this one is alive,

01:16:28 and I told the group this morning he's a butcher,

01:16:31 and when I go to Chicago at the ACS meeting, at the AACC meeting,

01:16:37 I'm going to go on to Rockford and get my free steak dinner that he gives me

01:16:41 every time I come to Rockford.

01:16:44 He weighed 861 grams, and I want you to read this, or I don't think you can.

01:16:50 That's the way you are.

01:16:51 Stomach capacity, 4 milliliters, empty time, 3 milliliters per hour.

01:16:55 Who would guess that?

01:16:57 The stomach capacity, how do we determine that?

01:17:00 Well, I took a syringe and saw how much I could put into the stomach,

01:17:04 and all I could get in was 4 milliliters.

01:17:06 Then I waited and sat there and tried to put more in

01:17:10 and plotted how much I could get into the stomach, 3 milliliters per hour.

01:17:14 I sat down with a pencil and paper, multiplied by 24,

01:17:18 and I said that I can't put more than 72 milliliters into this child,

01:17:22 and he needs at least 120 milliliters to survive.

01:17:26 So I said the rest has to go by twice.

01:17:29 So I stuck the needle in him.

01:17:32 I put in my mouth 1 milliliter of water at 8 hours.

01:17:37 You see, I didn't wait 24 hours.

01:17:40 1 milliliter of water until 5 milliliters,

01:17:45 then 2.5 milliliters, 2.5 percent lubricant water per hour for 24 hours.

01:17:52 So I was afraid 24 hours.

01:17:54 I didn't use any salt at all.

01:17:56 I was afraid because the book said if you give salt to children,

01:17:59 they get retrolateral fibroplasia.

01:18:02 That's exactly what they said, and I'll show you that.

01:18:05 Now, of course, it's nonsense, but that's what the book said.

01:18:09 Twice, by 15 days, I got the twice of the 30 milliliters,

01:18:14 2.5 percent of the 72 milliliters, 2.5 percent glucose,

01:18:19 and I also had some salt in there that doesn't seem to fit.

01:18:22 Now, I added cortisone because by that time,

01:18:26 from what's up to the course, I knew that they needed cortical support.

01:18:30 Cortisone was useless.

01:18:32 Four times a day, 1 milligram of slug,

01:18:35 and by the seventh day, the driver was called in

01:18:44 and told that the child wasn't breathing and that it wouldn't last longer.

01:18:48 But I wouldn't give up, and I called the anesthesiologist to work with me,

01:18:52 and he pumped the kid, and somehow or other,

01:18:55 I increased the amount of fluid that he got in,

01:18:59 and by the 13th day, we held him,

01:19:02 and I was able to get 84 milliliters by the 13th day of human breast milk.

01:19:07 His mother started giving milk, and I was able to do that.

01:19:11 By the 17th day, you notice he hasn't gained very much.

01:19:14 Breast milk is up to 120 milliliters,

01:19:17 and I kept putting a little salt in it all the time.

01:19:20 By the 18th day, up to 130 milliliters.

01:19:23 I've got him now.

01:19:25 With this amount, I can keep him alive indefinitely.

01:19:28 And then by the 24th day,

01:19:30 he had four-tenths of a gram of sodium chloride breast milk

01:19:33 and 150 milliliters of breast milk.

01:19:35 This sodium chloride was in all of these fluids,

01:19:38 and it's all messed up now.

01:19:41 On the 26th day, I noticed the following.

01:19:45 You come over here, you see a sodium 110,

01:19:48 you're not very happy about it,

01:19:50 and a chloride of 75.

01:19:52 There's adrenal immaturity.

01:19:54 I said, I've got to do something and get the chloride up.

01:19:59 So I didn't know what to do, so I gave him 5 milliliters of blood.

01:20:02 Why 5 milliliters of blood?

01:20:04 Because you're dealing with a 950-gram baby,

01:20:06 and that's like an adult giving him 3 units of blood.

01:20:12 So I noticed that without increasing anything,

01:20:17 it didn't do very much,

01:20:19 but let's turn to the next page.

01:20:21 I kept adding salt, hoping that I would get it up.

01:20:25 But I noticed this.

01:20:27 Sodium 135.

01:20:29 I was giving 5 cc of blood each day,

01:20:32 and all of a sudden the sodium jumped to 135 and 100.

01:20:36 Let's have the next page.

01:20:38 I drew the conclusion at that time

01:20:41 that there's something in blood that helps him hold the sodium.

01:20:45 In other words, I had discovered aldosterone but didn't know it.

01:20:49 Now, I said, what hormone could possibly be in blood that's helping him hold it?

01:20:54 It has to be something in the adrenal.

01:20:57 There was a lot of talk of a salt-containing hormone.

01:20:59 It didn't have a name yet,

01:21:01 but desoxychorticosterone had been isolated from animals.

01:21:05 I got some desoxychorticosterone and started to use that.

01:21:09 In that way, I was able to maintain the sodium at the chloride level.

01:21:14 You notice, here I have trouble again,

01:21:17 so I went back to the blood.

01:21:21 Where's the next slide?

01:21:26 There's another second slide that's missing there.

01:21:30 It should say, 30th day, and so on.

01:21:34 Eventually, on the 80th day, he went home.

01:21:38 The slides have gotten longer.

01:21:41 Let's have the next one.

01:21:43 Subsequent to that, Dr. Crawford, who is...

01:21:48 Let me put that back.

01:21:50 He said, if this works this way,

01:21:57 and these children need salt and some cortical support,

01:22:02 then let's try salt in the heavier infant

01:22:07 and see whether that cuts down this hospital stay.

01:22:10 These are the hospital stays.

01:22:12 A child weighing 2,000 grams...

01:22:15 This is 1,600. It's going down to smaller here.

01:22:18 1,630 grams should go home in 40 days.

01:22:27 We gave this child...

01:22:29 We filed two of them at the same time.

01:22:31 We gave this one 1 gram a day.

01:22:34 Mind you, right from the first day,

01:22:36 we were giving him a gram of salt, and that's good.

01:22:40 We filed him.

01:22:42 He lost the weight, like a normal family child,

01:22:45 and this one went home at the end of 20 days.

01:22:48 50% savings.

01:22:50 This one, we gave 2 grams.

01:22:52 We just said, we're going to push it.

01:22:55 Then we cut it back to 1 gram,

01:22:57 and he went home about the same time.

01:22:59 This child was in good condition on the 20th day.

01:23:02 So we discovered that if you gave salt

01:23:05 and tazoxicorticals to Rome...

01:23:08 We didn't give tazoxicorticals to Rome.

01:23:10 In an infant that big, we just used plain salt.

01:23:13 Then they went home early.

01:23:17 May I have the next slide, please?

01:23:25 With this study, 47 cases were...

01:23:31 were not chosen at random,

01:23:33 but represent those cases in which the physicians

01:23:35 chose to allow their cases to be studied.

01:23:38 I was working in all the hospitals,

01:23:40 and as soon as they got in trouble with a premature,

01:23:42 I get a phone call, we got a case for you.

01:23:45 And out of these cases, there were 5 deaths.

01:23:51 And a total of...

01:23:55 I think there were 47 survivors and 5 deaths.

01:23:58 And a total of over 50.

01:24:01 Now, 4 of them were dead on arrival.

01:24:03 One of them we killed.

01:24:05 You saw the one we killed, which we didn't do anything for.

01:24:09 We used watchful waiting,

01:24:11 recommended by the professors from Harvard.

01:24:16 And so...

01:24:20 This is just incredible.

01:24:22 As a result, when these statistics...

01:24:26 And of course, you add up all the other 200 and so infants that lived,

01:24:30 our statistics were incredible.

01:24:32 In other words, Rockford, Illinois,

01:24:34 now has the lowest mortality rate in the world,

01:24:38 in any city, in prematures, regardless of weight.

01:24:43 The state of Illinois decided that we were falsifying the records.

01:24:49 So they sent the representative down to Rockford to inspect.

01:24:52 And he wrote the foreword to this.

01:24:55 And you can read the foreword in here.

01:24:57 All I said to him was, go to the charts and read them.

01:25:00 And he came out shaking his head, and he said,

01:25:03 I have to report to people.

01:25:05 And he said, make a report to the state.

01:25:07 And that's how this report was made.

01:25:09 Originally, the state then asked that the methodology

01:25:13 and the normal value be put in the back.

01:25:16 And that gave rise eventually to the book called

01:25:18 Microtechniques of Clinical Chemistry.

01:25:21 But the conclusion here was this.

01:25:25 It is hoped, and I want to read this very carefully,

01:25:27 for what I'm going to say next.

01:25:29 It is hoped that this report will stimulate others

01:25:32 interested in the problem of prematurely

01:25:34 to undertake similar studies to prove or dispute our contention

01:25:38 that the solution to the problem of successful management

01:25:41 of prematurity lies in making available promptly

01:25:45 to the physician quantitative chemical data

01:25:48 so that he can use similar principles of fluid therapy

01:25:52 which have been successfully used in other children.

01:25:55 That was the conclusion of the report.

01:25:57 Now, as a result of this,

01:25:59 may I have the next slide, please?

01:26:01 There was an explosion.

01:26:03 Lots of things like,

01:26:06 the Court of Review of Pediatrics

01:26:08 collected 12 leading pediatricians in the country.

01:26:12 And each one gave his opinion of the book.

01:26:15 And they were all bad.

01:26:17 They all said that I was crazy,

01:26:19 that you can't give salt to prematures,

01:26:21 and that this is utter nonsense.

01:26:24 Because what I was doing was challenging them.

01:26:27 They were all leaving the prematures alone.

01:26:29 And if the premature couldn't take the blood from the bottle by mouth,

01:26:32 he was dead.

01:26:34 And what I was suggesting is one sentence.

01:26:38 All these injections that he had to get,

01:26:41 go over to the third floor and take a look,

01:26:45 and you'll see every crib has a nurse.

01:26:48 And they're taking care of the kid on a 24-hour basis, these prematures.

01:26:53 And I'm sure that saint over here

01:26:55 is doing a tremendous job in prematurity

01:26:59 because he's following me.

01:27:01 This was the title.

01:27:03 Why does a premature infant need adrenal cortical support?

01:27:06 Now, this was the yellow dog title

01:27:08 because I had never said that every premature infant needed adrenal cortical support.

01:27:14 I said the low-weight premature needed it.

01:27:18 And you could do it with salt alone if you wanted to,

01:27:21 but it was easier to do it with salt.

01:27:24 Nevertheless, this is what they wrote.

01:27:26 Now, in retrospect, after 40 years, this was correct.

01:27:32 The premature needs adrenal cortical support.

01:27:37 That is a fact.

01:27:38 May I have the next slide, please?

01:27:40 Whether you use salt or hormones.

01:27:42 Now, let me read you.

01:27:43 I'm thinking that the author, the editor, wrote this statement.

01:27:47 He's describing what I recommended.

01:27:50 Blood levels of electrolytes, CO2, protein, hematocrit, pH, sugar, and urea

01:27:54 are followed at frequent irregular intervals by study of fingertip or heel blood.

01:27:59 That's being done routinely in practically every hospital in the United States.

01:28:04 An attempt is made to maintain facilities on an around-the-clock basis.

01:28:08 That's the case in this hospital in Cincinnati here.

01:28:12 Microchemical methods and micro-bacteriological procedures.

01:28:18 Corrective fluids therapy is attempted on a quantitative basis.

01:28:22 I calculated in the back of the book how to calculate fluids for a two-pound premature.

01:28:27 An illustrated appendix describes the laboratory processes in detail.

01:28:31 In other words, at the request of the state of Illinois, I gave the procedures in the back.

01:28:37 Here's a typical page showing how to draw the blood, how to treat it.

01:28:41 I'm sure looking around at the same setup here that that's what they're doing.

01:28:46 May I have the next slide, please?

01:28:48 Now, this is one of the statements of one of the critics.

01:28:52 There were 12 of them, and each one was worse than the other.

01:28:57 Our feeling, in contrast to that of the authors, that prematures generally handle salt poorly.

01:29:02 They never gave the premature salt, so they didn't know.

01:29:06 And are just as likely to retain salt as to become dehydrated.

01:29:10 This is the reason why some of the pharmaceutical companies omit salt from their proprietary feeding products.

01:29:17 In other words, how could an infant live without salt?

01:29:21 The argument concerning early feeding approval still goes on.

01:29:24 We have had more satisfactory results in bone marrow and venom.

01:29:27 I was holding all peripheral edema, filled all fluids until peripheral edema disappears.

01:29:33 He's talking about the full-time infant, because the premature infant is not born with edema.

01:29:39 The water in a newborn baby is put in in the last month, in the ninth month,

01:29:44 and the children are born at 10 months on the assumption that the milk of the mother will not flow for at least two or three days.

01:29:51 A premature isn't born that way. He's born dehydrated, as recommended by Clifford and Smith.

01:29:59 Well, Smith was Clement Smith, who had written a book called The Premature.

01:30:03 I can say categorically that there isn't a single page of any truth in his book

01:30:09 that these infants vomit and aspirate most frequently when moderately dehydrated.

01:30:15 In other words, he said, that's one of the statements.

01:30:20 Now, let's have the next one.

01:30:25 The information deriving the study may be valuable.

01:30:28 Before adopting such a complex regime with all of the injections of fluid, etc.,

01:30:32 which is going on right now in this hospital,

01:30:35 what was wished to ensure that such a program of mass development was realized

01:30:39 over the rest of the developmental methods in current use in large groups of infants,

01:30:43 including every infant born alive,

01:30:55 the gross mortality rates in most centers now approximate the following.

01:30:59 1,000 grams or less, he says, 90 to 100 percent die.

01:31:05 In my study, 9 out of 10 survived.

01:31:08 I had one weighing 500 grams who survived.

01:31:11 Out of the 10, the heaviest one was the one you saw, weighing about 800 grams.

01:31:17 And that was what brought the state of Illinois down to my level.

01:31:21 45 to 55 percent died.

01:31:25 To take 1,500 grams, you've got well over 3 pounds.

01:31:30 And 1,500 to 2,000 grams, you've got 5 to 15 percent.

01:31:37 And that's his, in his place.

01:31:40 But you see, they were here with cheating.

01:31:43 Because if a child was born dead, they didn't count them.

01:31:46 If a child was, like in my case, 5 deaths, 4 of them were delivered dead to the hospital.

01:31:52 I counted them.

01:31:54 May I have the next slide, please?

01:31:57 This is another one.

01:31:59 One interesting statement is that the premature infant has an unusual susceptibility to dehydration.

01:32:05 And a dehydration, or in some cases, irrigation may explain what it was.

01:32:09 We have yet to observe this in five years.

01:32:11 They didn't observe it for a very good reason.

01:32:13 Because when the child died, they threw him in the trash basket or something.

01:32:17 They never really discovered the fact.

01:32:20 Why did he die?

01:32:21 They say, well, he was a premature infant.

01:32:23 It's like prematurity on his testicles.

01:32:26 As a matter of fact, most prematures seem to demonstrate birth.

01:32:31 That's maybe so, but I've never seen one.

01:32:34 This is a baby that remains for several hours and seems to slowly disappear on the successive 24 to 72 hours.

01:32:41 Rarely have we found a necessary to administer fluids within the first few days of life.

01:32:45 Indeed, most observers probably vote against the administration of fluids with a damaged premature.

01:32:50 Most, they say, put a damaged premature.

01:32:52 If the premature was a damaged, he would be the exception.

01:32:55 And I also would not give him fluids for fear of flight or fluid retention.

01:33:01 May I have the next slide, please?

01:33:04 Each one is different.

01:33:06 One is the Philadelphia Lion Hospital, Hopkins, Harvard, Yale.

01:33:11 An important contribution to this study seems to be the publication of microchemical methods determined in the very first case.

01:33:17 We are, however, not necessarily in agreement with the clinical study.

01:33:20 The evidence in Hopkins' work that increases sodium intakes adds to the increased danger of retroactive fibroplasia.

01:33:26 There's also evidence that repeated transfusions add to the danger of retroactive fibroplasia.

01:33:31 That's the nonsense that they wrote in these articles.

01:33:36 May I have the next slide?

01:33:37 Of course, retroactive fibroplasia has nothing to do with blood and has nothing to do with salt.

01:33:42 We do not find your small premature dehydrated.

01:33:47 You understand that a woman who has an abortion hasn't had fluids for 48 hours sometimes.

01:33:53 Obviously, the infant is born dehydrated.

01:33:56 Do they tend to dehydrate sufficiently?

01:33:59 Do they need peripheral fluids except in rare instances?

01:34:02 The loss of chlorides is not the usual finding in small premature.

01:34:06 I want to read that again.

01:34:08 The loss of chlorides is not the usual finding in small premature.

01:34:11 Because I'm going to read a rebuttal to that by some of these people.

01:34:16 On the contrary, I suspect normal saline will give them an excess of chloride, which they do not have it well.

01:34:22 I never used normal saline at any time in my studies.

01:34:26 I was always alluding it was 2.5% salt solution.

01:34:30 It says so up here.

01:34:31 May I have the next slide?

01:34:33 This is another one.

01:34:34 The work of Heffner regarding relationship between retroactive and high-sodium chloride

01:34:39 As an observation, that feeding a form of low-sodium content may be associated with regression of the vascular leakage of the ER.

01:34:47 That's utter nonsense.

01:34:49 Demands careful evaluation.

01:34:51 The measurement recommended by the President of the Office is in disagreement with Heffner.

01:34:55 And, of course, the law was in disagreement.

01:34:57 Unless a definite reduction in mortality can be demonstrated, it should not be encouraged unless we find out how we decide between two alternatives.

01:35:05 And, of course, he was making fun of the fact that I was saying that if you hydrate prematures and keep them at normal pH, they come home sooner.

01:35:15 May I have the next slide, please?

01:35:17 Considerable emphasis is placed on the so-called responsive interest to the administration of sodium chloride in this oxycodone-less world.

01:35:26 However, major was that the lowest values for serum carbon dioxide content in sodium were observed one week after.

01:35:33 The observations in this sample might almost be considered as evidence against the idea of adrenal immaturity.

01:35:40 May I have the next slide?

01:35:41 At that time, after reading all of this, I was a little nervous.

01:35:45 I said I chose the wrong words.

01:35:47 I should have used loss-solving, salt-losing syndrome, or something like that.

01:35:53 Inability to hold water.

01:35:55 But now, today, 40 years later, there's no question.

01:35:58 It's adrenal immaturity.

01:36:01 Now, this was the only man, and this was Daryl.

01:36:05 Daryl was a very intelligent pediatrician.

01:36:10 He was a friend of Edgman Kramer.

01:36:12 He knew me, and he knew that I would not publish something that I hadn't proven thoroughly.

01:36:18 So he wrote this.

01:36:20 He was one of the kindest ones.

01:36:22 The views of this article seem obviously heretical.

01:36:26 It appears to be a heretic, but he introduced a new idea.

01:36:29 I do not believe in throwing stones at heretics, although many are false prophets.

01:36:33 See?

01:36:34 He doesn't know what to make of what I'm saying.

01:36:36 The first and worst heresy is the thought that the premature infants can readily handle large loads of salt

01:36:43 and think that they need extra salt to survive.

01:36:46 That is true.

01:36:47 That statement is true.

01:36:48 I'll soon prove it.

01:36:49 May I have the next slide, please?

01:36:52 I went down with Dr. Crawford, and I was rather apologetic.

01:37:00 Not Dr. Crawford.

01:37:01 He worked with these prematures.

01:37:03 He has had 40 years of experience, and he said there's no question about it, that we are right.

01:37:09 Of course, in answering them, and some of you have gotten a copy of a reprint of this article in which I answer them,

01:37:19 the authors rephrase their work on the part of the premature infant need adrenal collateral support.

01:37:24 That was not the heretic.

01:37:26 The heretic was something about maintenance of electrolyte balance in infants.

01:37:33 They changed the heretic to read this to make me look bad.

01:37:36 But they didn't, because it turns out that they were doing me a favor.

01:37:42 We say, what's the stimulated interest in the application of the principle of floor therapy,

01:37:48 which has been successful in older children?

01:37:50 This was taken, they're quoting, directly out of the book.

01:37:53 Low-rate infants, especially in those low-rate ones where mortality statistics are high, and so on.

01:38:02 We go on and answer that.

01:38:03 May I have the next slide, please?

01:38:05 This is still more.

01:38:08 In many cases, after a 24-hour delay, the condition is irreversible, even when fluids were administered intravenously.

01:38:16 We couldn't resuscitate them after 24 hours, so we gave up on that.

01:38:21 This is from the answer to that.

01:38:23 May I have the next slide, please?

01:38:25 The best answer to that came from Burke.

01:38:28 He was the leading critic of this study, and he got a $50,000 grant to prove I was wrong.

01:38:35 He got on the phone one day, and he called me and said,

01:38:38 Nelson, I have only one thing to say.

01:38:40 You're absolutely right.

01:38:42 He referred to this paper, which he published in the Proceedings of the Staff of the Meeting of Male Clinics.

01:38:49 Reports of the failure of a premature infant, again, on a low-salt diet.

01:38:55 That's a big weight, 1,600 grams.

01:38:59 After he turned to salt, the brief period of waking was remarkable.

01:39:04 That 1,000 grams was gained in 20 days, giving him salt.

01:39:09 So he supported the idea that salt was necessary.

01:39:12 Now let's get to the next one.

01:39:14 This is the best one of all.

01:39:18 Clement Smith, who was the arch enemy, who was being attacked by me,

01:39:24 got a $100,000 grant from the NIH to prove that I was wrong.

01:39:29 And here's what he wrote.

01:39:32 O'Brien, Anson, and Smith have again shown emo-concentration associated with obvious physical signs

01:39:41 in premature infants not treated with fluids and a rising chloride level.

01:39:46 This was not observed in infants whose hydration was maintained.

01:39:50 Can you push this over?

01:39:53 By mists.

01:39:55 And he introduced, he now admitted in the article that they were dehydrated for the first time.

01:40:01 In his book, which he wrote, he said premature infants are born over-hydrated.

01:40:05 But now he admitted they were dehydrated and they needed fluids.

01:40:09 So I said to Crawford, I said, now that he's using mists, we will get him.

01:40:17 I gave Crawford the ammunition.

01:40:19 You know why?

01:40:20 Because in the mists they were using aloe vera.

01:40:23 And the fellow who made aloe vera was me.

01:40:26 And what I used in aloe vera was the sodium salt of octylphenol sulfate,

01:40:32 which I made from my doctorate thesis.

01:40:34 And I knew it was alkaline as hell.

01:40:36 So let me have the next slide, please.

01:40:41 I gave this slide to Crawford, who was the head pediatrician.

01:40:46 And this was, he took a child and he took the chemistry, sodium, potassium, chloride, pH.

01:40:54 This was the child he began with.

01:40:56 He did this with a normal child.

01:40:58 He then used mists.

01:41:00 And he used a full-time child because he didn't want to kill him.

01:41:03 At six hours, sodium was down 143, and the chloride had dropped.

01:41:08 And you can see that the pH, of course, started to show a little alkalosis.

01:41:13 At 12 hours, the child was in frank alkalosis, 148 sodium and 90 chloride.

01:41:20 And at 24 hours, he had 152 sodium and 85 chloride.

01:41:26 This killed mists.

01:41:28 All over the country you saw them spraying mists.

01:41:32 After this slide was shown at the pediatric meeting in Chicago,

01:41:37 Crawford ran home with his tail between his legs.

01:41:41 And that was the end of mists.

01:41:43 May I have the next slide?

01:41:46 Now, since that time, every year a paper comes out, at least one a year, sometimes two,

01:41:53 claiming that premature needs salt.

01:41:56 And a paper appeared by these people here in 1978.

01:42:03 It was reviewed in Pediatric Currents.

01:42:06 It said, these data suggest that the daily sodium requirement of immature sick kids

01:42:11 will be much higher than was previously thought.

01:42:14 Each one makes a discovery.

01:42:16 None of them refer to nails.

01:42:18 Essentially, the investigations say urinary sodium should be monitored

01:42:22 and sodium intake adjusted to prevent hyponatremia in the first days of life.

01:42:28 And if you read it carefully through, they're saying the same thing that I said in 1951.

01:42:34 May I have the next slide, please?

01:42:37 Nothing has been so documented.

01:42:39 Now, I bring this slide out to show what effect these people had.

01:42:44 I had an assistant by the name of Sidney Godfrey.

01:42:47 Sidney Godfrey said he needed a paper.

01:42:50 He wanted to apply for a job.

01:42:52 So I said, you can make an easy paper.

01:42:55 Just take a nail of blood collecting tube and go up on the floor

01:42:59 and collect the blood of over 50 or so newborn infants and do the hematogram.

01:43:06 But there was no data on hematograms, but he did that.

01:43:09 And he showed, of course, 60, 50, 60, and 90.

01:43:13 So he sent the paper into the Journal of Pediatrics.

01:43:18 Who should the editor be but Charles Levine,

01:43:21 a fellow whom I had castigated because of his high-protein milks.

01:43:26 So he rejected the paper and said,

01:43:28 if you take out the reference to Nadelson, I'll publish it.

01:43:31 But the paper was published without a reference to Nadelson.

01:43:34 That's why for the last 40 years there's been a blockade in the literature.

01:43:38 Nobody refers to Nadelson when it comes to this subject.

01:43:43 Now, the result of this work was this child was born not adrenally immature,

01:43:50 but adrenally insufficient.

01:43:52 In other words, the child was born with practically no adrenals.

01:43:56 The result was that the child had two siblings that had died.

01:44:01 Full-time children had died.

01:44:03 And this one finally was born.

01:44:05 And I made the diagnosis by analyzing the blood.

01:44:10 And I said the sodium chloride is low.

01:44:12 They have 65 chloride and 105 sodium.

01:44:17 The kid needs salt.

01:44:18 So the kid was given salt.

01:44:20 And then he was given some dioxycorticosterone.

01:44:23 But basically, since he could suck so many grams of salt over,

01:44:29 I don't know how much he was giving a day,

01:44:31 but he was giving him enough salt to maintain the level.

01:44:34 The child then went home.

01:44:36 And this is what the child looked like at about two years of age.

01:44:41 The child moved to Chicago.

01:44:43 And who should his doctor be but Dr. F.,

01:44:46 who was head of the pediatric division at Michael Reese Hospital.

01:44:51 Dr. F. said, Nadelson's crazy.

01:44:53 And he took away the salt from the kid and put her on a low-salt diet.

01:44:58 She was readmitted 48 hours later, maybe three days later, to Rockford.

01:45:04 They drove her to Rockford at 2 o'clock in the morning.

01:45:06 And with a circulatory collapse, the veins were all white.

01:45:10 I managed to get a little blood, and she had 65 chloride.

01:45:14 Before Dr. Crawford could get there and give the child a transfusion,

01:45:19 the child expired.

01:45:20 So this child was executed because of the fact that they refused to believe

01:45:25 that these children needed salt.

01:45:27 You may have the next slide, please.

01:45:30 Now, I took this picture not too long ago in a hospital.

01:45:34 I don't remember where.

01:45:35 But if you go up on the third floor here,

01:45:37 you'll get what you'll see.

01:45:39 They were talking about all these fluids.

01:45:41 The kids up on the floor here have twice as many as these.

01:45:45 They have attachments all over the body.

01:45:47 Dr. Mines was talking about getting data without invading the body

01:45:51 and getting blood.

01:45:52 The premature noise people were doing that all the time.

01:45:55 They're getting PCO2, PCO3.

01:45:58 They're getting PCO2, PO2, and other data by various types of electrodes.

01:46:04 This is what a premature looks like.

01:46:06 This is a pretty big one.

01:46:08 I would say that this is pretty close to maybe 2,000 grams or more.

01:46:16 The child has a polyethylene tube in him, and he has everything else.

01:46:22 May I have the next slide, please?

01:46:26 So I'm going to show this slide again.

01:46:28 Can you raise yourself?

01:46:31 It didn't drop.

01:46:32 It didn't drop.

01:46:33 I'm going to try to go backwards and then forwards.

01:46:38 The outcome of Nielsen's studies were those same points that I made before,

01:46:43 and I believe that I have shown two facts at least.

01:46:47 I've shown that the general feeling at that time was that salt

01:46:51 and water treatment to prematures was not an acceptable procedure

01:46:57 and that I was the first one to introduce that idea

01:47:00 and that that idea has now been shown to be the general practice.

01:47:04 You can't walk into a hospital anywhere in the United States

01:47:07 where they have an acute program for infants without seeing children look just like that

01:47:17 with polyethylene tubes and so on.

01:47:19 One of the critics said,

01:47:21 I would hate to put polyethylene tubes in all the children's noses.

01:47:25 It would develop rhinitis, infection,

01:47:27 and it gave a whole list of diseases that they would get with polyethylene tubes.

01:47:32 Well, it just isn't true.

01:47:34 You see, if you remove the tube periodically

01:47:37 and you wash it and clean it and put it back again.

01:47:40 So I went upstairs and I said to the kid there,

01:47:47 I said, you see this floor here that Seng has set up?

01:47:51 They said, yeah.

01:47:52 I said, I'm the grandfather of that.

01:47:55 But you have to tell them who taught Reggie Seng how to do calciums.

01:47:58 Pardon me?

01:47:59 You have to explain to everybody who taught Reggie Seng how to do calciums.

01:48:03 How to do calciums?

01:48:05 Remember he was at Michael Rees Hospital?

01:48:07 Well.

01:48:09 I was not the inventor of the calcium procedure.

01:48:18 No, no, but you showed Reggie Seng at Michael Rees Hospital how to do calciums.

01:48:23 Wasn't Reggie Seng a resident at Michael Rees?

01:48:26 He was at Michael Rees.

01:48:28 But we were doing it by atomic absorption by that time.

01:48:33 Incidentally, in that book that I have,

01:48:37 there is a single method that's used today,

01:48:40 and therefore what I'm saying is the clinical chemist is not known for the methodology

01:48:45 because the methodology of today is obsolete tomorrow.

01:48:49 The clinical chemist is known for what he does

01:48:52 in connection with developing new and better ways of treating disease

01:48:55 and working with a physician in solving these problems.

01:48:59 And I pride myself not on the methodology because that's all obsolete.

01:49:04 I pride myself on the fact that I was able to contribute to the treatment of hypercalcemia,

01:49:11 to the treatment of, in this particular case, in this area,

01:49:16 to the maintenance of the premature

01:49:19 and to the general maintenance of the newborn infants.

01:49:22 And that is the most important thing.

01:49:24 I couldn't have done it without the help of about 25 or 30 doctors.

01:49:29 And that's what the clinical chemist's job is,

01:49:33 to work with the medical staff in seeing that the patient gets a better care.

01:49:39 Thank you.

01:49:41 Thank you.

01:50:02 Thank you very much, Dr. Nadelson.

01:50:05 It was certainly a stimulating presentation

01:50:09 and almost all our hospitals, I don't mind, has a very active neonatal unit

01:50:13 with all of this testing done continually.

01:50:17 And I suppose in the next five or six years,

01:50:19 we're not going to have to use the drug lab to do all that.

01:50:22 The basic principles will still be there.

01:50:24 Thank you for doing this.

01:50:26 I think Mikey's going to be right this time, you know.

01:50:28 He's right.