Wesley Kingston Whitten

Oration | Address to Convocation

Dr. Wesley Kingston Whitten was born in Macksville, New South Wales, and attended Sydney University. Graduating in 1939 with a degree in veterinary science, Dr. Whitten is considered a pioneer in reproductive physiology. Dr. Whitten served four years as a captain in the Australian Army Veterinary Corps and later joined Australia's Commonwealth Scientific and Industrial Research Organisation to work on the reproduction of sheep.

In 1950 he became a faculty member of the Australian National University where he remained until 1961. As a faculty member his research focused on delayed implantation of lactating mice and his findings pioneered the study of mammalian pheromones and their receptor, the vomeronasal organ. From 1966 to 1978, he was associate director at the Jackson Laboratory in Bar Harbour, Maine. The author of over 100 publications, he was associate editor of both Biology of Reproduction and Journal of Experimental Zoology.

Two of his discoveries are so significant that his name has been given to them. Whitten's Medium allowed the culturing of mammalian eggs and a major methodological development in the study of oocyte maturation, fertilization and embryo development. All methods in these field today are based on Dr. Whitten's original work. The influence of sexual pheromones on murine reproduction, his discovery, is known as the Whitten Effect.

For his achievements Dr. Whitten was made a Fellow of the Australian Academy of Science in 1982 and was given the Pioneer Award of the International Society for Embryo Transfer in 1996.

In 1993, Dr. Whitten was awarded the prestigious Marshall Medal from the Society for the Study of Fertility. The award was established in 1963 following the suggestion of Sir Alan Parkes. It was to be awarded "from time to time by the Society to outstanding contributors to the study of fertility and reproduction".

It is a good morning exercise for a research scientist to discard a pet hypothesis every day before breakfast. It keeps him young." Inspecting our honorary graduand this morning, we see that Konrad Lorenz was right. In his life of scientific endeavour, Wes Whitten has developed and discarded many hypotheses, making others redundant by proving them correct. Lord Chesterfield wrote that "A man who has great knowledge from experience and observation is a being as different from and as superior to a man of mere book-knowledge, as a well-managed horse is to an ass." Dr. Whitten's basic research, driven by curiosity, proceeded so notably because, realizing the significance of chance observations, he followed them up.

His first degree was in veterinary science from the University of Sydney, south across the harbour from the animal haven of Taronga but close to the semilunar heaven of Bondi, where in youth he surfed not until he was tired out (as most of us would say) but, ever the scientist, "... until [his] glycogen stores were exhausted." After war service with the Australian Army Veterinary Corps, he studied reproduction in sheep before joining the Australian National University, where he downscaled the size of his research objects, studying the endocrinology of delayed reproduction in mice (a consummation devoutly to be wished). Overcrowding is the major problem of this world and to assuage this Dr. Whitten reasoned that a successful search for new contraceptives would facilitate the control of fertility in man and other pest species.

Horace Walpole wrote that the three Princes of Serendip had the unusual talent of "always making discoveries, by accidents and sagacity, of things they were not in quest of." Thus Dr. Whitten, using the pure water of Canberra, was first to achieve the in vitro fertilization and culture of mammalian embryos, something previously inhibited by the chlorinated water of other cities, while available eggs fresh from the henhouse provided nutrient albumen and supplied the unrecognized but necessarily rich levels of carbon dioxide. But there was more to the medium than this. While assuming that the embryos were anaerobic, he took the trouble to test this faulty supposition by adding calcium lactate to the culture medium, and achieved thereby embryonic growth through stages hitherto unrealized. Thus was Whitten's medium created, the standard in all embryonic culture experiments for the last half-century, allowing studies of development that would otherwise have been impossible. Modestly, Dr. Whitten has implicated chance; but chance, Mr. Chancellor, favours only the prepared mind.

Gender selection by the opposite sex is, fortunately, a key factor in mammalian evolution. Male magpies are not family-oriented, but when Dr. Whitten gave them estrogens, they went all broody and started to build nests. Throughout the animal kingdom the ordering of life depends on the chemical senses and Dr. Whitten has explored the role of chemistry in the growth, development and social activity of animals over the last forty years in Australia, Newfoundland and Bar Harbour, Maine. He has shown that female mice caged together experience inhibition of their normal sexual cycles, while upon exposure to male mice (or their urine) their cycles recommence with profligate urgency, a pattern of behaviour appropriately not researched in humans. This is the Whitten effect, discovered after careful preparation, meticulous observation and the use of low technology (specifically, disposable toothpicks), demonstrating for the first time in mammals the subtle imperatives of pheromones. Again, his own 20-20 olfactory memory, primed by early days in the Australian outback, allowed him to recognize the red foxes' yellow visiting cards in the snows of Maine. This led to the synthesis of their active olfactory ingredient and to further experiments with it in the wild, producing emphatic responses from other foxes, which further substantiated the pheromonal puissance.

This honorary graduand shows every attribute of the scholar-scientist: wide-pervading interests; a knowledge base expanded by experience and observation; receptiveness to the challenges of the unusual; the creative ordering of discordancy; simple practicality in finding methods for their solution and an overall motivating purpose, transcending the drudgery of the laboratory in pursuit of a higher goal. Dr. Whitten's quiet work on single dividing cells has benefitted the world's divided populations by revealing the earliest processes of the ingenious machine of nature, allowing mankind a glimpse of divine control.

Albert Camus believed that "Great ideas come into the world on doves' feet. If we listen closely, we will distinguish the gentle whisper of life and hope." Mr. Chancellor, the Whitten is a popular name of the Wayfarer tree. I present to you a scientist who has steered his prepared mind through the way of productive research; and science has fared well. His record of practical insights has led others to emulate his simple, logical approach to research questions. To honour this progenitor of our potential control of the first steps of life, this provider of reasonable hope that we people of the earth shall have the means to manage our numbers responsibly, I present to you, for the degree of doctor of science, honoris causa, Wesley Kingston Whitten.

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I am proud and delighted to have been chosen to receive this honorary degree from MUN because I have great respect for this institution and province and because it recognizes research that I started half a century ago and half a world away in New South Wales, Australia. I emphasize the "new" in the name because it indicates that, like Newfoundland, New South Wales is remote from the traditional centers of learning and in a new environment where we face new problems while trying to avoid errors that have become entrenched elsewhere (for example, in Darwin College, Cambridge, I could not get breakfast before 9 a.m. whereas my research mice mated before 5 a.m.).

I expect that some of my audience hope to learn how to become successful researchers and all I can say with confidence is "be born lucky, work hard, and choose suitable projects and a conducive environment." The research should be within one's own capabilities and within a time frame that allows adequate testing of hypotheses. Most of my contributions come from testing false hypotheses. In my early experiments, mouse embryos were slow to develop so I gave them extra oxygen and they all died; whereas, the controls survived. I reasoned that, if the controls were anaerobic, they would not be able to metabolize lactate. So, I tested embryos with this substrate only to find that they love the stuff! I was awed to be the first to witness the hatching of mammalian embryos in vitro. In 1955 I published a note in Nature describing the first chemically defined medium for embryos, which became known as Whitten's Medium. In 1996, when I was given the Pioneer Award by the International Embryo Transfer Society, I was presented with a bronze sculpture, done by a well-known Canadian artist, that depicts this amazing event.

Few scientists spend time in the animal house, but I made my best known observations there with a toothpick as my only apparatus. After pairing adult mice, I used it to search for copulation plugs. From the data I acquired, I deduced that the estrous cycles were shortened by something associated with the presence of males. It was subsequently shown to be a protein in the urine. Four decades later, my resulting paper had been cited more than 1,000 times and the phenomenon had become known as the Whitten Effect. It should have been called the Male Mouse Effect. This opened new fields of study: mammalian pheromones, and the role of the vomeronasal organ as a pheromone receptor. Pheromones are substances produced by one member of a species that induce a response in other members of that species. The work became even more interesting when histocompatibility genes were shown to be involved. In 1993 The Society for the Study of Fertility awarded me The Marshall Medal. Appropriately, Marshall was the author of the first test on reproductive physiology and a pioneer on the study of communication between sexes of vertebrates, but had never obtained evidence of chemical communication.

My observations on pheromones were incidental to my major interest, the development in vitro of mammalian embryos from fertilization to implantation. This aim was achieved after 15 years of work and paved the way for innovations in the treatment of human fertility with IVF, GIFT, ICSI and for the promise of therapeutic cloning from stem cells. IVF and embryo transfer are used throughout the world's livestock industries. These studies also contribute to basic genetics and to experimental embryology by making it possible to fuse embryos of different strains, producing some visible mosaics such as piebalds. I was able to apply my highschool algebra to model these three-dimensional mosaics, which look more like marble cake than currant buns.

Not all of the developments from my experiments please me. Some have yet to be proven safe, and some are being used to add to the over population of this planet. So one of my early aims to use IVF to screen for contraceptives should still be pursued.

My career has been unusual. When I graduated in veterinary science in 1993, Australia was facing a serious new economic problem - infertility in sheep. A variety of clover had come to Australia initially as packing material for Italian furniture. It was subsequently grown as sheep fodder, and it did so well that sheep farmers expected to increase their flocks substantially. Instead, lambing percentages dropped dramatically. It was at this time that I was given a scholarship, and then a permanent appointment, to develop research in sheep reproduction. We eventually overcame the infertility problem, but we missed the opportunity to identify and market that first oral phyto-contraceptive. If we had, we would have "been in clover!"

I soon found that work with sheep was too slow to test hypotheses and accepted a hybrid appointment at the Australian National University to direct the Animal Breeding Program and funding to carry out cognate research. This also gave opportunities for rewarding collaborations on such projects as the control of rabbits by myxomatosis. I focused primarily on delayed implantation of embryos in lactating mice where, by developing the in vitro culture system, I successfully separated maternal and embryonic factors and began in vitro studies of early mammalian embryology.

With international recognition for my contributions, I was invited to join the scientific staff of the Jackson Laboratory in Maine, the world's Mecca for inbred mice. I spent 16 years there and became associate director for research. In collaboration with postdoctoral fellows, I developed a medium for in vitro fertilization and overcame the 2-cell block to produce the first viable and fertile young. With Stetson Carter, my assistant, we were able to skew sex ratios by selection or by experimental manipulation to produce 25 per cent males, or 75 per cent males, respectively. These experiments also produced a small percentage of hermaphrodites, a few of which were male on one side of the body and female on the other. Using the technique for transplanting mouse ovaries developed by colleague LeRoy Stevens, we were able to obtain sperm and oocytes from a single hermaphrodite and so produce by self-fertilization the first mammalian clone. In this case the clone was composed of fertile males and females - exciting from a scientific perspective, but scary within the societal context.

One of my most recent findings occurred in the animal house when I discovered an ovarian tumor in a 26-day-old mouse while carrying out a pheromone assay. This tumor turned out to be genetic and has provided a model for the study of juvenile granulosa cell tumors of humans with very interesting genetic and endocrine implications.

So, it was 40 years ago when I received a D.Sc. for my published work from the University of Sydney. It was then that my young daughter, now a graduate of MUN, and present here today, boasted that her daddy had been doctored. To qualify for today's second doctoring, I can only conclude that some gonadal stem cells must have escaped the knife and could be the subject of a dissertation for my next doctorate.

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