Pushing the Limit:
An Interview with Dr. Leonard Hayflick
By David Jay Brown
Leonard Hayflick, Ph.D., is a microbiologist whose research revolutionized cell biology, and helped to provide a scientific foundation for the field of cellular gerontology (or cytogerontology)–the study of aging at the cellular level. Dr. Hayflick discovered that cultured normal human cells can only divide a finite number of times, after which they become senescent. This limited capacity for cell division is now known as the ‘Hayflick limit’, and this discovery has enabled other researchers to make significant progress towards understanding the molecular mechanisms of aging and cancer.
Following this groundbreaking discovery, Dr. Hayflick developed the first normal human diploid fibroblast cell strains. One of these–called WI-38–is still the most widely used normal human cell strain in the world. Dr. Hayflick was also the first to produce a vaccine (the oral polio vaccine) from these cells. WI-38 cells, or similar human-cell strains, are used today for the manufacture of most human virus vaccines throughout the world–including poliomyelitis, rubella, rubeola, adenoviruses, measles, mumps, and rabies vaccines.
Approximately a billion people have received virus vaccine doses produced on WI-38 or similar diploid cell strains, yet Dr. Hayflick makes no profit from this. In fact, he was accused by the government of stealing its’ property when he asked for packaging and mailing costs from pharmaceutical manufacturers and viral research labs. Dr. Hayflick’s inability to patent and profit from his development–because at the time in 1962, one could not patent living matter–became the foundation for his lawsuit against the Federal government, which, after six years of litigation he won with an out-of-court settlement. This lawsuit helped to establish the discoverers or inventors intellectual property rights that researchers in the biotech industry take for granted today.
Dr. Hayflick also discovered the cause of primary atypical pneumonia (“walking pneumonia”). Dr. Hayflick demonstrated that this illness is caused by a member of the smallest free-living class of microorganisms–which he named Mycoplasma pneumoniae–and not by a virus, as was previously believed. Dr. Hayflick demonstrated this by growing these microorganisms in a medium that he developed.
Dr. Hayflick earned his Ph.D. at the University of Pennsylvania in 1956. He served ten years as an associate member of the Wistar Institute and two years as Assistant Professor of Research Medicine at the University of Pennsylvania. In 1968 he was appointed Professor of Medical Microbiology at the Stanford University School of Medicine, and he is currently a professor of anatomy on the faculty of the University of California, San Francisco.
Dr. Hayflick was the Editor-in-Chief of Experimental Gerontology for thirteen years, president of the Gerontological Society of America, chairman of the Scientific Review Board of the American Federation for Aging Research, and a founding member and chairman of the executive committee of the Council of the National Institute on Aging. He has received more than 25 major awards–including the 1991 Sandoz Prize for Gerontological research and the Presidential Award from the International Organization of Mycoplasmology. Dr. Hayflick is a fellow of the American Association for the Advancement of Science, and is one of the principal advisors for the Ageless Animals Project–which is directed by John Guerin, who was also interviewed for this collection.
Dr Hayflick is the author of over 225 scientific papers and reviews–some of which are the among the most cited scientific papers in human history. He is also the author of the popular book How and Why We Age (Ballantine Books, 1994), which has been translated into ten languages. The story of Dr. Hayflick’s distinguished and controversial career is chronicled in a book by Debbie Bookchin and Jim Schumacher called The Virus and the Vaccine (St. Martin’s Press, 2004), and in Stephen Hall’sMerchants of Immortality (Houghton Mifflin, 2003). Dr. Hayflick is currently working on a book about his experiences as scientist for Cambridge University Press.
I interviewed Dr. Hayflick on April 27, 2005. Dr. Hayflick is an elegant speaker. I was excited to hear firsthand about his discoveries, and greatly appreciated his patience in answering questions that I’m sure he’s answered a thousand times before, making sure that I understood every detail. We spoke about how the fetal cells that he cultured were used for viral research, vaccine production, cancer research and the causes of aging, and why he thinks that researching the causes of aging is more important than directing biomedical research efforts to the study of disease.
David: What inspired your interest in the biology of aging?
Dr. Hayflick: My interest in the biology of aging was a pure accident; it evolved from a discovery that I made in the early 1960s. The discovery that I made flew in the face of existing dogma at the time–dogma that was entrenched for more than sixty years–and because I was convinced that I had overthrown that dogma, the experiments that I did required some explanation, or at least some speculation as to what they meant. After conducting a number of experiments that excluded many possibilities that seemed reasonable, I was left with one possibility that I could not exclude, and that was that the observation that I had made was telling me something about longevity determination and/or aging. So I speculated on that possibility in the paper that I published with my colleague Paul Moorhead in 1962.
Then I began to realize that the field of aging at that time was, to put it mildly, an impoverished field. There were perhaps a dozen people in this country, at the most, who were working in this field–or, at least, who would admit in public that they were working in this field, because at that time the climate was such that to admit in public that you were working in the field of aging was tantamount to committing professional suicide. So people that worked in the field of aging often did so in the closet. Then because of my speculation, and because of the popularity that this paper began to assume, I was contacted by one or two of the dozen people working in the field of aging to speak at some of their congresses.
One person in particular was Dr. Nathan Shock, who is generally regarded as the father of modern gerontology in the United States. We became very good friends, and it was through him that I became introduced to other people in the field, in particular members of the Gerontological Society of America. This is the professional organization that people in the field of biology of aging and geriatric medicine, as well as the social and psychological aspects of aging–indeed, every aspect of aging–are members. So I went to their meetings, initially when I was invited to speak, and I began to realize that I was becoming a biogerontologist. This was not by intention, as I mentioned at the outset, by accident, and I became very interested in the subject. The rest is history.
David: Can you talk a little about how the fetal cells that you cultured were used for viral research and vaccine production?
Dr. Hayflick: At the time I was working at the Wistar Institute in Philadelphia, which was directed by a man named Hilary Koprowski, who was a pioneer in polio vaccine research. (In fact, contrary to popular belief, Koprowski was the first person to develop, and actually test in humans, a live virus vaccine. It was not Albert Sabin as is popularly believed.) A fair proportion of the research activities at the Wistar Institute–by no means all of them–were conducted around virus vaccine research because of Koprowski’s interest, so I couldn’t help but learn more and more about human vaccine development and the problems therein.
And as luck would have it, my work with the normal human fetal cells directly impacted on the problems with human virus vaccines that emerged at that time. I suppose one could argue that was just a lucky break that I made the discovery that I did in the right place at the right time, because of what was emerging in the late ‘50s and early ‘60s with the polio vaccine. To give you some idea of the atmosphere at the time, poliovirus research was, I suppose, equivalent in the minds of scientists and the general public then as stem cell research is today. In other words, every other hour you read something about it or heard something about it.
So, first let me say what the problems were in vaccines at the time so that you’ll understand how my work fitted into it. The problem that was emerging at the time was centered on the fact that monkey kidney cells were used for the preparation of the virus vaccine. As I’m sure you know, viruses can only replicate on living cells; they cannot replicate on dead material as can bacteria. So, because you need lots of viruses in order to make vaccines, you need lots of cells to make lots of viruses. The cells that were chosen by Jonas Salk and others at the time for vaccine production were primary monkey kidney cells. There were other vaccines that used other types of cells. For example, the flu vaccine was made using embryonated eggs, and it still is today.
But the polio vaccine was made in monkey kidney cells. The