An Interview about Sir John B. Gurdon – Stem Cells

Jul 16, 2019 by

Michael F. Shaughnessy

1) One individual who not only won the Nobel Prize but was named “Sir” in Great Britain was Sir John B. Gurdon.  He was born in England- but apparently had some very early difficulties. Tell us about his early education.

Sir Dr. John Bertrand Gurdon, a 2012 Nobel Laureate in Medicine or Physiology, was born in the small rural village of Dippenhall, in Hampshire county (now Surrey), England, on the second day of October, in the year 1933. John’s parents were Marjorie Byass and William Nathaniel Gurdon, a banker with a substantial inheritance from an endowment.

John Gurdon’s earliest educational experience was based on a sort of home-schooling instruction, complete with private tutors. John and his older sister Catherine had been shipped to England’s countryside during World War II, as this region of the country, southern England, was a prime target for German Blitz bombing.

In a keynote memoir, published in the prestigious Annual Reviews series devoted to cellular and developmental biology, Dr. Gurdon writes about his early schooling at a preparatory school, Edgeborough, neglected to teach him the biological sciences before his entry into Eaton, a prestigious college preparatory school, at age 13, where biology was not taught there, as well, until 15 years of age. His experiences at Eaton were less than desirable. First, he was bullied by classmates, and he was staunchly discouraged by his teachers to pursue the academic discipline of biology.

Gurdon’s main interests at the time appeared to be moths and butterflies, a passion he had had since early childhood. Thus, upon graduation from university at Oxford, he eagerly applied to their Entomology program for graduate school. His application for Ph.D. school was rejected.

Thus, in 1956, he applied instead to Oxford’s graduate program in Embryology, and his application was accepted! As a newly minted 22-year old graduate student, Gurdon entered the research laboratory of Prof. Michail Fischberg. It was here in Dr. Fischberg’s laboratory where young Gurdon learned the technique of transplanting cellular nuclei from the embryos of frogs, known as Xenopus, into living host eggs! In 1960, John B. Gurdon took his Ph.D. degree from Oxford.

2) Interestingly enough, there are some records of some of his instructors expressing some doubt that he would ever make it as a scientist. Do we have some records of his early evaluations?

John Gurdon’s biology instructor at Eaton is recorded to have described John’s plan to become a biological scientist as “ridiculous” and a “sheer waste of time” not only for John, but especially for his future Biology teachers! According to another source, an interview he gave to a reporter, Gurdon placed academically at the very bottom of about 250 students of his Biology course at Eaton.

At the age of 15, his academic performance at Eaton was so appalling, he was accordingly told that he had absolutely no abilities whatsoever to undertake any sort of academic subjects in any kind of depth, and he was consequently placed in a classroom with other students who were at the bottom, like himself. In this new class, however, he was placed at the bottom of even that class. In fact, he was ranked at the very bottom of the entire school!

Furthermore, he was told by his teachers that there was no sense in trying to make a career out of anything having to do with science, as he was just “no good” at it. He was made, therefore, to study Latin and ancient Greek, instead of Biology, not because he had any acumen for those topics but because there were extra teachers available to teach them. He was made to abandon a topic he loved, Science, for now focusing on topics that held no interest for him.

He was given a year to try to get back into his science-based courses, a discipline in which he had held a life-long passion. He recalled that he felt sorry for his parents who paid his tuition money, for all of this trouble.

The educational ordeal had been brutal and its effects long-lasting.

The negative student evaluation by the teacher was to be framed and shared with the world. The student, Dr. John Gurdon, in later years was himself to provide an assessment of his own about his former teacher.

Soon after the Nobel, Sir Dr. John Gurdon had recalled that the discouraging teacher, the one who had placed him at the bottom of his class and had recorded his scientific career options as “hopeless,” was, in fact, a terrible teacher in that he had taught the material incorrectly. Much of the course material delivered by the teacher was factually wrong!

Thus, many years later Sir Dr. Gurdon was to candidly note in an interview regarding his Nobel Prize that he had, on the contrary, felt quite fortunate during that time in Eaton, because he was no longer under auspices of such a terrible teacher—it had been, instead, a great relief for him to have been removed from the course.

To make matters worse, however, when the time arrived to consider higher education at university, Gurdon was informed in no uncertain terms that while he was certainly welcome at Oxford University, it was nevertheless under the proviso that he NOT concentrate his studies in Latin or Greek, as he appeared to have performed less than adequately in these subjects on his entrance examinations.

He was permitted, however, to concentrate on learning Zoology, the study of animals, at Oxford. Unfortunately, with his lack of a proper secondary preparation in the biological discipline, Gurdon had to spend an extra year of study to make up for the deficiency. Nevertheless, he took his undergraduate degree from Oxford, majoring in Zoology.

Gurdon’s troubles with his previous preparatory education plagued him as he applied to graduate school. His undergraduate record was less than stellar, and he was rejected from the Ph.D. program in Entomology at Oxford but later accepted in the Embryology Department where he successfully completed all requirements for the doctorate, in 1960. The thesis work was to lead ultimately to the Nobel.

3) The family motto “virtus viget in arduis” (virtue thrives in adversity) is interesting in that Sir John Gurdon had to undergo a great deal of adversity and difficulty during his life. Tell us about some of the adversity he had to face?

The Gurdon family follows a long and distinguished aristocratic ancestral line. As you pointed out, the family motto is “virtus viget in arduis” (Latin for virtue flourishes in adversity), which originates as far back in history as 1199 A.D. The Gurdon family name goes back to this ancient time in England, with his earliest known ancestor, Bertrand de Gurdon, and to ancient France, to about 1400 A.D, with a one Jean de Gurdon as another known ancestor.

As you noted in your previous question, John Gurdon’s early educational experience was fraught with “disaster” and had been an exceedingly appalling predicament for him. The experience left him traumatized for many years to come, openly speaking of it in blunt terms, even after the Nobel.

While his first foray into his Ph.D. thesis project was met with technically challenging laboratory protocols, trying unsuccessfully at first to perform nuclear transfer between somatic cells of the Xenopus frogs, Gurdon nevertheless persevered and eventually overcame each of the technical obstacles. Part of the problem was dealing with, as he referred to it, a “jelly-like” type of material that emerged during his experiments and was impenetrable to his micro-injection needles. Fortunately, the problem was solved when a new microscope, one that was fitted with a new UV lamp on it, was purchased. When the scope’s UV lamp was turned on to low wavelength emissions, the UV light dissipated the jelly, making it possible to conduct the micro-injections of the nuclei.

After successfully attaining his Ph.D. he had yearned to obtain postdoctoral training in the laboratory of the famous Dr. Renato Dulbecco, but was apparently turned away by the departmental head because Dr. Gurdon did have a firm foundation in the field virology, the study of viruses. Thus, Dr. Gurdon accepted a postdoctoral position at the California Institute of Technology (Caltech) working under Prof. Robert Edgar studying the genetics of bacteriophages. He found the work unsatisfying and resigned after only one year.

Another source of adversity had to do with Dr. Gurdon’s early animal cloning work in graduate school. He was soundly criticized for the work, even by investigators who had developed the methodology that Gurdon had made use of but having arrived at the exact opposite conclusions that Gurdon had reached. Fortunately, Gurdon’s experimental system had been strongly supported by a reportable genetic marker, which the other laboratory did have not have available at the time.

This particular criticism aside, Gurdon’s cloning work was then condemned by none other than his former lab mate, Dr. Jim Watson, perhaps rightly, as foreseeing a shocking situation that was akin to eugenics. The controversy came to a head later with the cloning of a well-known animal, a sheep named “Dolly.” Dr. Watson asked derisively whether we were going to see next a clone of new “Einsteins or Raquel Welches.” While biomedical scientists decry such human cloning, the work of Gurdon generated an air of hysteria. Not even Gurdon was advocating such a thing, of course, but other cell biologists were thinking out loud, based on Gurdon’s frog cloning work, about possibly cloning lower mammals. One merely needed to make the next leap to the cloning of humans!

Another bout with adversity had to do with the stem cells, the use of which many non-scientific groups criticized, especially with the embryonic type of stem cells. The stem cells made excellent progenitors for potential development into clinically useful tissues or even organs, but the idea was greatly criticized as unethical. These criticisms waned with the later finding by Dr. Gurdon’s co-Nobel Laureate, Dr. Shinya Yamanaka, who managed to develop an experimental system for converting non-embryonic mature stem cells back to immature primitive stem cells, without the need for any sort of embryos. This particular criticism, i.e., a putative need for embryos to get stem cells, had been an unnecessary one from the very start, because actual embryos were never actually needed. Immature stem cells could always have been obtained directly from placental tissue, i.e., tissue that’s routinely discarded after every single birthing process anyway.

4) From Eton to Oxford to Cambridge- he seemed to make the rounds of the best schools in England. What did he study at each university?

Eaton at the time of Dr. Gurdon’s tenure was an exclusive boarding school that was geared to the preparation of young students for entry into university. At the age of 15, Gurdon was enrolled at this institution, and his stay there was unsettling. He experienced bullying by students and terrible teaching by teachers. His passion for science was almost stymied by being forced to learn other topics that he found neither interesting nor of significance. Misunderstood from the very beginning of his entry to Eaton about his aptitude for biological science, he was removed from his science courses and made to study Latin and ancient Greek. The experience was so profoundly adverse that he was said to have actually framed one of his negative student evaluations by a teacher, from the Eaton years.

At Oxford, Gurdon took his Ph.D. degree, in 1960. It had been an elegant and groundbreaking thesis project. As a graduate student there, he gained an expertise in transplantation methodology of cellular nuclei in laboratory frogs called Xenopus, creating the first clone of a genetically identical frog, and demonstrating in an elegant fashion the ability of a cell to multiply and make each of the various somatic cell types of an animal. He had found that a transplanted nucleus could remember where it had come from and direct the production of an embryo specific to its origin rather than its host. The host cells had been reprogrammed!

When his former graduate advisor, Dr. Fischberg, left Oxford, Dr. Gurdon was asked to replace him. He accepted the offer and became an assistant lecturer, in 1962.

At Cambridge, Dr. Gurdon became a group leader, in 1971, of the Cell Biology Division at the institution’s Medical Research Council’s Laboratory for Molecular Biology. It was (and still is) a world-class and prestigious research facility. In 1983, Dr. Gurdon was promoted to full professor supported by the John Humphrey Plummer endowment, becoming the Plummer Professor of cell biology at Cambridge’s Zoology Department. Then, in 1990, he became departmental chair at the Wellcome Trust Cancer Research Campaign sponsored Institute of Cancer and Developmental Biology. In 2001, this institution was renamed to The Gurdon Institute.

One notable field of study at Cambridge by Dr. Gurdon was his pioneering work with RNA. In Dr. Gurdon’s laboratory work they used microneedles and injected the oocyte egg cells of their frog Xenopus with certain strings of RNA. The RNA-injected oocytes could actually use the RNA to make proteins as directed by the egg’s translational machinery! This methodology is still widely used to this day to study the physiological properties of proteins expressed in the Xenopus oocytes.

5) By the same token, he seemed to encounter a lively life- traveling from New York to California on the famous Route 66.  What did he encounter along the way?

The Route 66 trip taken in 1960 by the newly minted postdoctoral fellow Dr. Gurdon epitomizes an excellent example of the sort of activity one expects from an adventurous-minded spirit. He was taking the road trip from New York to California, in order to start his new position as a postdoc in the Caltech laboratory of Prof. R. Edgar, to study phage genetics. The new postdoc offer had been inspired from a visit to the Fischberg lab by the very famous Dr. George Beadle, 1958 Nobel Laureate, for his work pertaining to the notion that a gene specifies an enzyme—the so-called “one gene one enzyme” hypothesis.

Dr. Gurdon had purchased a used Chevrolet car for the cross-country road trip. Driving along the historical Route 66, Dr. Gurdon paid visits to various scientific luminaries. One such luminary was the notable Dr. Alexander Brink at the University of Wisconsin, at Madison, U.S. As a result of the visit, Dr. Gurdon became lifelong friends with Dr. Brink and his wife Joyce, and for many years after the road trip he would periodically visit the Brinks at their second home in Florida during the winter times.

Also visited by Dr. Gurdon during his historic Route 66 road trip was the famous Dr. Robert Briggs, who was housed at the University of Indiana, in Bloomington, in the U.S. Working with Dr. Thomas J. King, Dr. Briggs had been involved in developing nuclear transplantation techniques, a protocol of which Dr. Gurdon had effectively used in graduate school at Oxford.

Also at Indiana, during the famous Route 66 sojourn, Dr. Gurdon met Dr. Tracy M. Sonneborn, who was to elegantly work out the genetic behavior involved in the cellular differentiation inside the nucleus during the developmental stages in organisms of the Paramecium and Tetrahymena genera. In his memoir, Dr. Gurdon recalled how all members of the Sonneborn lab had picked up smoking of the pipe, as sort of an unspoken and endearing dedication to their research mentor.

6) Behind every successful man is a woman- and how did his wife contribute to his academic and professional success?

In 1962, Jean Elizabeth Margaret Curtis and John Gurdon met in Oxford, England, soon after his arrival to a post as assistant lecturer in their Zoology department. The couple had sired two children, a daughter named Aurea and a son named William. When Dr. Gurdon accepted the prestigious position of Mastership at Magdalene College, in 1985, Jean Gurdon took it upon herself to make sure that she entertained each and every undergraduate at the college. In so doing she would invite twenty undergraduates at a time to a weekly Sunday lunch, prepared by herself. She also acquired an amicable affiliation with each of the college’s personnel. Together with Dr. Gurdon declining pay for the Mastership and with Jean’s support, both teaching and administrative duties were minimized, and it permitted time to focus on scientific research. The end result of these activities was that Magdalene College at Cambridge enjoyed a high degree of faculty and staff morale during their tenureship.

7) British university systems are quite different from U.S. systems- and apparently Sir John Gurdon had to navigate a number of administrative concerns as well as research and teaching concerns. What do we know about all this?

Taking the advice of the famous Dr. Max Perutz, who headed the MRC Laboratory of Molecular Biology, in Cambridge, Dr. Gurdon declined to accept a professorship offer at the Cambridge’s Zoology department. The post would have been a prestigious one for Dr. Gurdon, as it had once been occupied by another famous scientist by the name of Sir Alan Hodgkin. However, Dr. Perutz had advised Dr. Gurdon that such an undertaking would most certainly kill his research program because he would be largely “crippled by university administration.”

Interestingly, while Dr. Gurdon was at the Wellcome CRC Institute, he had expanded the laboratory facilities with collaborator Prof. Ron Laskey by inviting others to participate in the collaboration, namely, Drs. Michael Akam, Martin Evans, Janet Heasman, and Chris Wylie. It was a monumental undertaking, requiring significant alterations in administrative duties. The research team decided to invoke the successful management style of Dr. Perutz. First, the team established a chairmanship structure, rather than a directorship. Next, they recruited younger promising scientists to become group leaders, giving these investigators opportunities to flourish by allowing them to focus on their research programs.

8) Through the miracle of modern technology, we can actually hear Sir John Gurdon talking about his receiving the Nobel Prize- the link is below. But could you perhaps summarize and explain why he was awarded the Nobel Prize and his relationship to “stem cells.”

There are two types of stem cells: the somatic type (adult), and the embryonic type. In general, these stem cells have two important properties: first, they are undifferentiated, and second, they are pluripotent.

Let’s consider the undifferentiation property of stem cells first. It simply means that a stem cell has no specialized function or structure to it. In this sense, a stem cell is said to be in a primitive state. The second property, pluripotency, means that the stem cell has the potential to become specialized, by differentiating into new types of cells and picking up new and specialized cellular functions. The stem cells are vastly important for these and other reasons. The stem cells can be used to generate badly needed specialized cells for use chemotherapeutically. They can also be quite beneficial for learning about life’s basic processes and for medical applications.

In the natural world, stem cells are the starter cells for the development of organisms. An egg that’s fertilized by sperm are at first primitive types of stem cells, undifferentiated but pluripotent, and they begin the painstaking process of forming a new mature organism by invoking the various cellular, tissue, and organ specializations. The fertilized stem cell has a nucleus with its specialization information already embedded, a condition known as nuclear programming.

In short, Dr. Gurdon discovered that if he could transfer a nucleus from a cell to another cell that has had its own nucleus removed, he could reprogram the newly injected unfertilized cell to undergo differentiation but for a completely different developmental program! Furthermore, he found that his protocol of nuclear transplantation resulted in animal progeny being genetically identical, and in so doing, he cloned higher organisms!

Dr. Gurdon’s Nobel Prize winning work at Oxford was done as follows. First, he took out the nucleus from the frog eggs and in their place he put in other nuclei that had been taken from growing tadpole gut cells, i.e., mature somatic cells. Then, the graduate student Gurdon let the transplanted frog eggs grow and develop. The result was an experimental production of new frogs, all of whom were genetically identical. He had, in fact, created a clone of frogs!

With the accompanying work of co-Nobel Laureate from Kyoto University, Dr. Shinya Yamanaka, who showed that he and Dr. Kazutoshi Takahashi could actually convert adult somatic cells into embryonic-behaving stem cells, complete with their undifferentiated states, it made Dr. Gurdon’s own pioneering work even more meaningful from a biomedical science standpoint. This new type of stem cell and its accompanying conversion system that had been developed by Drs. Yamanaka and Takahashi has been called induced pluripotent stem cells, or iPS cells. They reprogrammed adult somatic cells, which had already been differentiated, into iPS cells by artificially introducing several genes which encode special proteins called transcription factors, such as c-Myc, Klf4, Oct4, and Sox2. These transcription factors were produced in the injected cells, and they worked to mediate the induction of the pluripotent state, making primitive stem cells out of adult cells. This new work eliminated the ethical concerns raised by many and made the work of Dr. Gurdon relevant.

The nuclear transfer technique of Dr. Gurdon’s might be applied to introduce key reprogramming machinery in order to replace lost somatic cells or tissue in medical patients. Dr. Yamanaka’s work makes this approach significantly feasible. In theory, a patient with a medical disease might have hope. First, cells from the patient can be removed, converted into stem cells, fixed with Gurdon’s nuclear transfer method, allowed to differentiate with the correct cell type and then re-introduced back into the patient.

The approach might even be useful in replacing the conventional approach of organ and tissue transplantation! In this case, the grafts would actually be the patient’s own corrected cells, and, thus, a detrimental immune response and transplant rejection would be circumvented.

Another promising approach may be to use these systems of Drs. Gurdon and Yamanaka to learn about the cellular mechanism of a given medical disease. Then, potential medicines can be developed and screened for prospective therapies.

9) What have I neglected to ask about this Nobel Prize winner?

In an interview of Dr. Gurdon after the receipt of the Nobel, he conveyed the story about how he found out he was to get the coveted award. Before the official Nobel Prize announcement was made, there had been already rumors that he had gotten it. He conveyed the story that, at first, he received a phone call in the middle of the night from a reporter asking him how he felt about getting the Nobel Prize. When he told the reporter that he hadn’t heard about it, the surprised reporter replied that, well, he’d call back later.

The next phone call came from a Swedish person informing officially him of the Nobel award; Dr. Gurdon thought it might be a hoax! After all, there had been the rumors flying about.

That day, however, Dr. Gurdon was not to be completely convinced about the Nobel until he went to the laboratory where it was looked up on the Internet at the Nobel Prize web site. Only then, were he and his laboratory personnel convinced that day.

A great multitude of students, postdocs, and colleagues have all attested to Dr. Gurdon’s amicability. Such is the esteem for Dr. Gurdon that a large group of biomedical investigators published a multiple article volume in the journal Differentiation, with each article dedicated to this great scientist, the science, and to the kindheartedness of an immensely pleasant human being. In the series of papers in the special volume, many a grateful scientist communicated a great degree of gratitude to Sir Gurdon for having been given a chance by him to prove themselves scientifically when perhaps they might have felt less than deserving. The tribute is poignant.

You Tube: – for future study and in depth reference:

Sir John B. Gurdon

Sir John B. Gurdon – Nobel Lecture: The Egg and the Nucleus: A Battle for Supremacy – NobelPrize.orgwww.nobelprize.org The Nobel Prize in Physiology or Medicine 2012 was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka “for the discovery that mature cells can be reprogrammed to become pluripotent”.

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