Veterinarian won Nobel for immunology research

Dr. Peter C. Doherty continues studies, writes books for lay audience
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The only veterinarian to win a Nobel Prize, Dr. Peter C. Doherty was a state veterinary officer in Australia before embarking on a career in immunology research.

In his book "The Beginner's Guide to Winning the Nobel Prize" and in a recent interview with JAVMA News, Dr. Doherty described his experience with, and the global importance of, scientific discovery.

The Nobel Foundation awarded its 1996 prize in physiology or medicine to Dr. Doherty and Rolf M. Zinkernagel, MD, of Switzerland for their discovery in the early '70s of how T cells recognize virus-infected cells by looking for variants in certain molecules—histocompatibility antigens—on the surface of infected cells.

Dr. Peter C. Doherty
Peter C. Doherty
(Photos courtesy of St. Jude Children's Research Hospital)

Since 1988, Dr. Doherty had been a member of the Department of Immunology at St. Jude Children's Research Hospital in Memphis. He now spends most of the year at home in Australia as a professor in the Department of Microbiology and Immunology at the University of Melbourne Faculty of Medicine, Dentistry, and Health Sciences, and he devotes much of his time to writing books about science for a lay audience.

"Life at its best is an adventure, a voyage of discovery," Dr. Doherty wrote in "The Beginner's Guide." "What could be more gratifying than to discover, describe, and explain some basic principle that no human being has ever understood before? This is the stuff of true science. Those societies that foster and harness that passion will be the prosperous, knowledge-based economies of the future."

Early life and career

Born in 1940, Dr. Doherty grew up in the Australian state of Queensland. A visit during high school to the University of Queensland School of Veterinary Science piqued his interest in veterinary medicine. In Australia, students begin professional training directly after high school.

"I made the decision to go to the vet school at age 16 and, influenced by an older cousin who was a medical researcher, decided that I wanted to do research on the diseases of food-producing animals," Dr. Doherty said. "As an immature adolescent, spending my time around sick people had no appeal."

Dr. Doherty hoped to conduct research that would help feed the world, although he later reflected that he could have been happy as a large animal practitioner. In fact, his career led him to the realm of basic research.

On earning his BVSc degree in 1966, Dr. Doherty worked for the state for five years to repay support for his studies. After a few months in the field, he moved to the state veterinary laboratory, where he did diagnostic pathology and studied bovine leptospirosis and avian viruses.

In 1967, Dr. Doherty took a position in experimental pathology at Scotland's Moredun Research Institute, where he did diagnostic neuropathology and studied louping ill virus in sheep. He earned his doctoral degree in pathology in 1970.

In 1972, to improve his knowledge of immunology, he became a research fellow at the John Curtin School of Medical Research back in Australia.

"My personality is such that I like to go after things in depth, I like to understand what's happening," Dr. Doherty said.

In particular, Dr. Doherty wanted to learn about T cells to better his understanding of the immune response to viruses.

The big discovery

At the JCSMR, Dr. Doherty met Dr. Zinkernagel, another research fellow. The two decided to partner on studies of the mouse's immune response to viruses.

Their key experiment involved infecting multiple strains of mice with a virus. They then studied, in vitro, the T cells developed by the mice to kill cells infected with the virus.

To their surprise, Drs. Doherty and Zinkernagel found that T cells developed in any one strain of mice to kill infected cells would not kill infected cells from other strains of mice.

Scientists had long known that T cells would kill even healthy cells from a foreign individual. This reaction is triggered by the T cells' identification of certain molecules on the surface of the foreign cells, called histocompatibility antigens, which vary among individuals.

Following their experiment, Drs. Doherty and Zinkernagel concluded that the purpose of histocompatibility antigens is actually to allow T cells to recognize the body's own healthy cells.

As part of the body's immune response, viral infection of a cell must trigger a change in the histocompatibility antigens on the cell's surface, they reasoned. Then, T cells target infected cells by recognizing the virus-altered histocompatibility antigens.

These T cells would no longer look for other variant or foreign histocompatibility antigens. Thus, in the experiment, T cells that developed to kill virus-infected cells in one strain of mice would not kill infected cells from another strain of mice.

"We knew right off that we had a big discovery and did a great deal to publicize our findings and interpretation," Dr. Doherty said. "We reasoned that we had indeed discovered how T cell recognition works at the operational level."

Drs. Doherty and Zinkernagel published their findings in the journal Nature in 1974. Their interpretation was controversial, as many scientists thought the histocompatibility antigens might have another purpose, but the two researchers conducted additional experiments that supported their conclusion.

Later, other scientists would determine that virus-infected cells incorporate fragments of viruses directly into the histocompatibility antigens on the cell surface to signal infection to T cells.

Midcareer, Nobel Prize

Not long after their big discovery, Drs. Doherty and Zinkernagel went on to other institutions. In 1975, Dr. Doherty accepted a position at the Wistar Institute in Philadelphia. While there, he also collaborated with researchers at the University of Pennsylvania. He studied diseases ranging from influenza to rabies to multiple sclerosis.

In 1982, Dr. Doherty returned to the JCSMR as head of the Department of Experimental Pathology. Focusing again on immunology research, he moved to St. Jude Children's Research Hospital in 1988. From the late '80s to the early '90s, he also served on the board of what is now the International Livestock Research Institute.

Dr. Doherty was in Tennessee in 1996 when he received the call informing him that he and Dr. Zinkernagel had won the Nobel Prize for their experiments more than two decades earlier.

"My personal view of the prize is that, like many science laureates, I was recognised for my part in making a breakthrough discovery that changed the prevailing view," Dr. Doherty wrote in "The Beginner's Guide."

In 2002, Dr. Doherty joined the faculty of the University of Melbourne. He continues his studies in immunology today at St. Jude and the University of Melbourne.

"Biological science over the last decade has been enormously exciting because of the tremendous advances in molecular science and molecular technology," Dr. Doherty said. "And so you go to the most basic systems you can, and you study them in as much depth as you can, and try and understand actually what's happening."

Current endeavors

Influenza has been the subject of much of Dr. Doherty's research.

"We've used diseases to probe how the immune system works, but over the last couple of decades we've focused largely on influenza," Dr. Doherty said. "It's a very important practical problem as well as a good way of accessing the complexities of immune response."

Influenza is the main pandemic threat for humans, Dr. Doherty noted, and avian influenza has caused enormous economic losses in developing countries that have had to cull millions of chickens.

Dr. Doherty has stepped back from research somewhat in recent years to commit more time to writing books that communicate the value and values of science to a lay audience.

"The Beginner's Guide to Winning the Nobel Prize," which came out in 2005, drew on Dr. Doherty's own story to explore the why and how of the scientific discovery process. His concerns about climate change and thoughts on various other issues were the subject of "A Light History of Hot Air," which came out in 2007.

Two other books are due out next year on themes involving infectious disease. "Sentinel Chicken" is the tentative title of a book partly concerning birds as sentinels of disease. The other book is a guide to pandemics in a question-and-answer format.

Since winning the Nobel Prize, Dr. Doherty has spoken often to veterinary audiences. He tries to make veterinary students aware of the possibility of a research career but not necessarily to suggest that they go in that direction.

"My attitude toward the veterinary profession is I think it's a great profession, it's one of the great caring professions," Dr. Doherty said.

Legends in Veterinary Medicine

This article is the last of the "Legends in Veterinary Medicine" series of JAVMA news profiles in honor of World Veterinary Year. The series has profiled the following individuals:

  • Jan. 1: Claude Bourgelat
  • Feb. 1: Dr. Edmond Isidore Entinne Nocard
  • March 1: Dr. William Tyson Kendall
  • April 1: Dr. Andrew Smith
  • May 1: Dr. John McFadyean
  • June 1: Dr. Aleen Cust
  • July 1: Dr. James Alfred Wight (James Herriot)
  • Aug. 1: Dr. Douglas C. Blood
  • Sept. 1: Dr. Dawda Kairaba Jawara
  • Oct. 1: Dr. Bernhard Lauritz Frederik Bang
  • Nov. 1: Dr. Aline Schunemann de Aluja
  • Dec. 1: Dr. Peter C. Doherty