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Dr. Leonard Hayflick

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 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’s Merchants of Immortality (Houghton Mifflin, 2003). Dr. Hayflick is currently working on a book about his experiences as scientist for Cambridge University Press.

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.

Q: 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.

Q: Knowing what you know today, what sort of role do you think the limit on cell divisions that you discovered plays in the human aging process?

Dr. Hayflick: I think it plays an essential role. I think that the failure to understand its key role is based on the failure of most biogerontologists—and certainly most scientists—to understand the difference between aging and longevity determination, something that people should be aware of, but they’re not.You have to understand that distinction in order to understand my answer to your question, and it’s this. When you buy your Mercedes-Benz for a hundred thousand dollars, and drive it off the showroom floor you have a certain expectation about its longevity—namely, it damn well better drive well for eight or ten years without requiring major repairs, or you’ve been fleeced. When I drive my Yugo off of the showroom floor, and I paid five or ten thousand dollars for it, I have a completely different expectation about its longevity. I think you will intuitively understand why the longevity of your Merc and my Yugo are different—namely, different design, better workmanship, and better materials used in the Merc as opposed to the Yugo.

Now when those two machines are driven off the showroom floor the same process begins to occur, and that is the aging process, which means loss of molecular fidelity, or loss of molecular integrity over time. So the aging process is going to probably start earlier, and be more profound, in the Yugo than it will be in the Merc, because the longevity determinants are completely different in both kinds of cars. Now that concept lifts over to biology, and it’s just as true in biology as it is in inanimate objects. This is key to understanding the answer to your question.

The finite lifetime of cultured, normal human and animal cells, is a reflection of the maximum capability of that cell lineage to replicate, which is rarely—and I would argue—never reached, in real life because the aging process will kill the individual well in advance of that maximum number of divisions. There’s ample evidence for that. There are literally hundreds and hundreds of papers in the scientific literature that describe the changes that occur in normal human cells as they approach their loss of replicative capacity, and many of those hundreds and hundreds of changes are similar to the changes that occur in humans as we age. So if you argue that the cells go through fifty doublings, the changes begin to appear at, let’s say, the fifteenth or twentieth doubling, and become more and more apparent or emphasized up to the fiftieth doubling. Those are age changes. But the limit on the cells’ capability of replication is a reflection of the longevity determining process.

Q: Many people believe that individuals with progeria appear to suffer from a kind of accelerated aging process.

Dr. Hayflick: That’s the orthodox belief. It’s a knee-jerk reaction, and I don’t believe it’s true. I think that the best way to describe it is as biological McCarthyism—guilt by association.Q: What do you think is happening with progeric individuals?

Dr. Hayflick: I think that there’s ample evidence that it has a genetic basis. I think the features that make it look like accelerated aging are simply coincidental with some of the aging processes, but by no means all of them. There are many pathologies known in medicine that share similar clinical manifestations but have totally different etiologies.There are many people, who like me are reluctant to believe the symptoms of progeria are accelerated aging phenomena. They might bear on longevity determinants. They probably do, but there’s no universal agreement that those clinical manifestations are absolutely aging phenomena.

Q: I would imagine that many people believe it largely because of their appearance. Children with progeria look uncannily like old men and women, with balding heads and wrinkled skin, and they appear to suffer from many of the symptoms of old age. The photographs that I’ve seen are particularly striking.

Dr. Hayflick: Yes, but you can find photographs of two different pathologies, with two different etiologies that look similar. I mean, if a person gets hit by a bus, and their legs are crippled, and they’re walking around on crutches, and I pull somebody else out of the wings who has suffered from polio who is also walking on crutches, you’re not going to tell me they’re caused by the same agency.Q: What do you think are the primary causes of aging?

Dr. Hayflick: It’s very simple. We know the cause of aging, despite it appearing to be a mystery to most people. First of all, let me tell you what aging is and then I think the cause will be implicit. In animals that reach a fixed size in adulthood, aging is the random systemic loss of molecular fidelity, that after reproductive maturity, accumulates to levels that eventually exceed repair, turnover, or maintenance capacity.That’s the definition. It’s the progressive loss of molecular fidelity that increases vulnerability to age-associated diseases. So that’s the answer.

Q: What do you think causes that “random systemic loss of molecular fidelity?”

Dr. Hayflick: What causes that loss of fidelity is based on the fact that complex biological molecules are kept in a state of fidelity as a result of a variety of chemical forces and various chemical bonds—van der Waals forces and other well-known bonds that keep molecules together. It is also well known that the energetics—the energy that keeps those bonds in the state that they’re in, in molecules that are functioning—do not last forever. They last for varying periods of time—from as short as nanoseconds for ATP to years for collagen—so that there’s a spectrum of energy levels in biological molecules. We have elaborate maintenance, turnover, and repair systems to keep those molecules in their correct functional state.However, after reproductive maturation molecular errors begin to accumulate and exceed repair capacity for a very simple reason. There’s no need to keep those molecules in a perfect state after reproductive maturity, because the animal possessing those molecules has already done what nature intends for it to do, and that is to reproduce. The proof of that statement is that for 99.99 percent of the time that we’ve been human we’ve had a life expectancy of less than twenty years. It’s only been within the blink of an eye, on an evolutionary time scale, that we’ve had life expectations greater than that.

Q: Do you think that aging is actually a process that evolved?

Dr. Hayflick: No, aging is something that was never intended for us to see in the first place. It is an artifact of civilization. Aging only occurs in humans, and in the animals that you and I choose to protect—like zoo animals, domesticated animals and pets. It does not happen in the wild. We were intended to die at the age of thirty, but we’ve learned how to deal with the causes of our death such that we have revealed, teleologically, a process that we were never intended to see in the first place. And now we’ve got to live with it.

Q: Why do you think that researching the causes of aging is more important than directing biomedical research efforts to the study of disease?

Dr. Hayflick: Because the goal of aging research should not be—and I believe that it’s simply illogical to believe that it could be—to increase human longevity. That is, I should say, the goal of aging research should not be to intervene with the aging process and thereby increase longevity. The goal of biogerontological research should be to discover why an old cell is more vulnerable to pathology than is a young cell, and that key question is not being addressed by anybody on the planet at the moment. The reason it’s important should be obvious.When every physician in the world (of course I’m exaggerating, but I’m not too far off the mark) wakes up in the morning, they say this to themselves: The greatest risk factor for the leading causes of death—that is cardiovascular disease, stroke, and cancer—is the aging process. There’s no physician on the planet who will dispute that. So I have a very simple-minded question: Why is the funding for research on the fundamentals of the biology of aging microscopic when compared to funding for research on the leading causes of death?

Q: That’s a very good question.

Dr. Hayflick: It’s such a good question that whenever I show it on a slide [during a lecture] the physicians become slack-jawed and have no answer. But I think I know what the answer is.Q: What do you think it is?

Dr. Hayflick: Misunderstanding, greed, and power. Researchers in the fields of cardiovascular disease, stroke, and cancer require funding—after all this is one of our major industries. They don’t want to undermine that industry or change careers to become biogerontologists. Now they might not know this consciously, or realize consciously that that’s what’s happening, but it is. You can’t sell a senator or a representative on funding for the aging process. You can sell them on funding for cardiovascular disease, stroke, and cancer because either they or someone they know has one of them. They don’t know that the underlying process that makes them vulnerable to those leading causes of death is the aging process, because of a huge failure to educate them.Q: I recently interviewed John Guerin, the director of the Ageless Animals Project. What do you think we can learn from studying animals that don’t appear to age, like rockfish and turtles?

Dr. Hayflick: Well, I would hope that we could learn what the longevity determining processes are at the molecular level, and how the energetics of key molecules are maintained for periods of time in those animals that are unattainable in mammals.Q: What do you think is some of the most important aging research that is currently going on?

Dr. Hayflick: I rather think that the most important aging research is not being done today. I think a lot of the research being done today is misleading, especially the large area of work being done with invertebrates, namely worms and flies. There’s almost a weekly announcement by one of the workers in the field that they discovered a new gene for aging, and I think that’s absolute nonsense. There are no genes for aging. Most people don’t understand the difference between aging and longevity determinants. Genes control development and indirectly longevity. They do not control aging. I would defend that position by another simple analogy, and that is to ask people who believe that genes cause aging to show me in the blueprints for their automobile where it is written, telling their automobile how to age.There are no such directions in blueprints. Why? Because the process is a spontaneous process. It requires no instructions, and the same is true in biological material. The only reason that animals of different species live longer than others is because of the differences in the longevity determinants. That is, the characteristics of molecules at the time of reproductive maturation including the level of repair turnover and maintenance systems to operate.

Q: What are you currently working on?

Dr. Hayflick: I’m doing a lot of theoretical work, because I no longer have a wet lab. I’ve accumulated so much data, and I’m working on many of theoretical aspects, some of which I’ve already discussed with you.I’m also preparing to do another book. I’ve been asked to do a book by Cambridge University Press on my experiences as a scientist, because I’ve had some unique experiences—a couple of which I mentioned to you only briefly. The book is going to be sort of a memoir, but built around three subject areas, which I was fortunate enough to be either a pioneer, or was witness to, and these are: the emergence of tissue culture or cell culture as a scientific discipline, the emergence of vaccine technology, and the emergence of the field of aging. Since I happened to be present at all three births, roughly, and know a lot of scandalous stories, it should be fun.

David Jay Brown is the author of four volumes of interviews with leading-edge thinkers, Mavericks of the MindVoices from the EdgeConversations on the Edge of the Apocalypse, and Mavericks of Medicine. (Mavericks of Medicine will be published by Smart Publications as a book in late 2006.) He is also the author of two science fiction novels, Brainchild and Virus. David holds a master’s degree in psychobiology from New York University, and was responsible for the California-based research in two of British biologist Rupert Sheldrake’s bestselling books on unexplained phenomena in science: Dogs That Know When Their Owners Are Coming Home and The Sense of Being Stared At. To find out more about David’s work visit his award-winning web site: