Oral history interview with Christine E. Holt

  • 1995-Oct-25 – 1995-Oct-27
Photograph of Christine E. Holt

Christine E. Holt was born and raised in Wylam, a small village in Northumberland in the north of England, the youngest of three siblings. Her mother was a homemaker; her father was a naval sea captain during World War II, who then worked in the safe business and then the shipping business. She enjoyed exploring nature surrounding her home with her older brother, spending some time badger-watching, and she also played the piano. She attended British public schools (the equivalent of American private schools), and at the age of ten she was enrolled in a boarding school in which she stayed until she was sixteen. She enjoyed sports, including rounders and netball, and in school she split her focus between literature and the arts, and biology, but not other sciences; she had an interest in anthropology as well that was heightened by two trips to Africa during summer holidays. Holt's biology teacher at her college preparatory school taught with an outdated syllabus and so Holt decided to teach herself biology using Michael B. V. Roberts's textbook, Biology: A Functional Approach. She matriculated at the University of Newcastle upon Tyne to study zoology but then transferred to the University of Sussex, where she had opportunities to talk directly with professors like John Maynard Smith and was under the tutelage of Michael F. Land who encouraged her to undertake graduate studies. She received a very competitive Science Research Council fellowship for her doctoral studies and chose to work with John H. Scholes at the Medical Research Council (MRC) Cell Biophysics Unit in an attempt to unify her interests in genetics and neurobiology. At the MRC Holt faced challenges establishing Xenopus lines, though she was able to use radioactively-labeled amino acids to trace axon development. William A. Harris introduced her to the concept of using an electrophysiological mapping system with Xenopus, after which she decided to undertake her postdoctoral studies with him at the University of California, San Diego (and, subsequently, they married). Her research focus in Harris's lab was, predominantly, disproving the mechanospatial theory of brain development and contributing to the reaffirmation of Roger W. Sperry's chemoaffinity theory, which argued that every cell in the retina was specified with a different tag that matched a complementary tag in the tectum. From there she went on to another fellowship with Colin Blakemore at Oxford University to study mammalian cell development, through which she realized the impracticality of using hamsters to investigate early brain development and also the inability to demonstrate axon—tectum chemoaffinity in chicken culture. She then returned to San Diego as a researcher and, later, a professor. Soon after her fellowships and her return to San Diego, Holt and Harris spent a sabbatical with Friedrich Bonhoeffer at the Max-Plank-Institut für Entwicklungsbiologie in Tübingen, Germany, where Holt used time-lapsed video to observe Xenopus retinal axon in vivo and she investigated the possibility of guidepost cells in brain development. Soon after her return to San Diego, Holt received the Pew Scholars Program in the Biomedical Sciences award, with which she worked on developing the method of in vivo lipofection. At the end of the interview Holt talks about her work on the effects of perturbation of cell adhesion molecules on axon growth; establishing a lab; spending a year with John Gurdon at the Wellcome Cancer Research Campaign Institute in Cambridge, England; the journal review process; and balancing her career and family life and issues that women in the sciences face. The interview concludes with more of Holt's thoughts on science including the discovery that fibroblast growth factor (FGF) can prevent axons from recognizing their target; growth factor receptors' role in target recognition; and the connection of glycosaminoglycans to FGF receptor function.

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