Rejuvenation Research 2014.17:479-480. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 02/06/15. For personal use only.
REJUVENATION RESEARCH Volume 17, Number 6, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/rej.2014.1646
Editorial
Denham Harman (1916–2014): A Personal Reflection Aubrey D.N.J. de Grey
‘‘If I have seen further, it is only by standing on the shoulders of giants’’ —Isaac Newton
B
y the time you read this, many words will have been written in eulogy of Dr. Denham Harman, originator of the free radical theory of aging, who died in November at the age of 98. Since much of that material will have been penned by colleagues who knew him longer and better than I did, it would be superfluous for me to offer a standard obituary. My own memories of, and debt to, Denham are perhaps a little unusual, though, hence this brief tribute. First, my personal view is that the pinnacle of Denham’s contribution to the biology of aging is not quite as it is generally portrayed. To be sure, his 1954 insight1 that living organisms might generate highly reactive free radicals as byproducts of metabolism, which would then be prone to damage essential molecules such as DNA, was absolutely seminal: Arguably it was the first time that anyone had truly identified a plausible biochemical mechanism for the life-long accumulation of damage that eventually causes physiological decline and death. But Denham was not alone in thinking along these lines in the mid-1950s, and it is pretty much certain that if he had not proposed this when he did, others would have done so within a year or three— notwithstanding the fact that very few other gerontologists of the time knew (or felt the need to know) enough chemistry even to understand the idea for many years thereafter. It was a very different story 18 years later, when Denham published a virtually unnoticed article2 suggesting that mitochondria, and specifically mitochondrial DNA, might be the major locus of free radical damage leading to aging. This insight was followed up by virtually no one until it was revived3 (without attribution) in 1989, following which it became one of the dominant themes in biogerontology (and, incidentally, my own major area of interest when I entered the field in the mid-1990s). Had Denham been less far ahead of his time, and been able to bring his new idea to the attention and interest of more of his colleagues, progress in our field might have been a good deal faster. There is also another aspect of Denham’s 1972 paper that merits our attention. Far too often in science, including biogerontology, a researcher rises to prominence on the
back of a single important contribution and then spends the rest of his or her career defending it with a level of vehemence not wholly justified by available data. Denham did not make that mistake. His own experiments on the impact of dietary anti-oxidants on rodent longevity were overall rather underwhelming. A lesser scientist in that predicament might have swept this under the carpet and bashed on regardless, or else gone too far the other way and abandoned the theory wholesale, as some are inclined to do with the entire free radical theory nowadays. Denham, instead, accepted the need to reconcile the data that originally inspired the theory with the results he was obtaining, and he didn’t shrink from that quest until he had found a solution, namely the possibility that free radicals do their damage in a compartment to which anti-oxidants lack access. It should be particularly borne in mind that 1972 was only a few years after mitochondria had been shown4 to contain DNA at all, and moreover that that discovery was not made by gerontologists. As such, this is a sterling example of the value of exploring beyond one’s core area of interest and expertise and thereby encouraging cross-disciplinary ideas to emerge, a dictum that I have followed assiduously throughout my career and which unequivocally underpins most of my key contributions. Denham’s status as one of the very few people whom I not only admire but elevate to the status of role model arises not only from his science, however, but also from his community leadership. One reason why he was such a voice in the wilderness in 1972 was that he was in, well, the wilderness, having recently deserted the Gerontological Society of America (GSA), and founded a new organization, the American Aging Association (AGE). Why did he do this? One shortcoming that the GSA had, and indeed has to this day, is that biology is a very minor component of its activities and its meetings, hugely overshadowed by the hordes of clinicians, sociologists, and policy experts who form the Society’s other sections; AGE, by contrast, was from the outset dedicated solely to the biology of aging. But perhaps more importantly, 1970 was a time when biogerontology
SENS Research Foundation, Mountain View, California.
479
Rejuvenation Research 2014.17:479-480. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 02/06/15. For personal use only.
480
was becoming increasingly ‘‘politically correct’’ as efforts grew to elevate its prestige in the corridors of power, and to a great extent that meant distancing itself from the quest to actually do something about aging. In short, the indisputably daunting complexity of aging and the lack of a coherent biomedical research path to postponing it had led to a fear that the discussion of such matters, as however long-term a goal, risked bringing the field into disrepute. Harman was one of very few prominent members of the field who dissented from this, and arguably the one who did the most— and sacrificed the most in terms of his standing—in his efforts to counteract it. AGE was for many years shunned by many in the field, and only in the late 1990s did it truly begin to rival the GSA, but by now it has become generally recognized as unsurpassed in its scientific quality—and it has done so without ever drawing back from its interventionfocused roots. Moreover, Denham took this campaign global in 1985 by forming the International Association of Biomedical Gerontology, a conference series whose 10th iteration I was privileged to take on, allowing me to launch the ongoing series of Cambridge SENS meetings, an achievement that I rate among my proudest. In conclusion, let me just say that as a gerontologist who is first and foremost driven by the humanitarian quest to free us all of the tyranny of aging, I can think of no forerunner
DE GREY
whose example is more clearly one to follow than Denham Harman. If, by my scientific and outreach contributions, I have inspired a new army of talented younger individuals to join this crusade, it is substantially by emulating the ways in which Denham inspired me. He will not be forgotten. References
1. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol 1956;11:298–300. 2. Harman D. The biologic clock: The mitochondria? J Am Geriatr Soc 1972;20:145–147. 3. Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet 1989;1:642–645. 4. Nass S, Nass MMK. An electron histochemical study of mitochondrial fibrous inclusions. J R Microsc Soc 1963;81: 209–213.
Address correspondence to: Aubrey D.N.J. de Grey SENS Research Foundation 110 Pioneer Way Mountain View, CA 94041 E-mail: [email protected]
REJUVENATION RESEARCH Volume 17, Number 6, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/rej.2014.1646
Editorial
Denham Harman (1916–2014): A Personal Reflection Aubrey D.N.J. de Grey
‘‘If I have seen further, it is only by standing on the shoulders of giants’’ —Isaac Newton
B
y the time you read this, many words will have been written in eulogy of Dr. Denham Harman, originator of the free radical theory of aging, who died in November at the age of 98. Since much of that material will have been penned by colleagues who knew him longer and better than I did, it would be superfluous for me to offer a standard obituary. My own memories of, and debt to, Denham are perhaps a little unusual, though, hence this brief tribute. First, my personal view is that the pinnacle of Denham’s contribution to the biology of aging is not quite as it is generally portrayed. To be sure, his 1954 insight1 that living organisms might generate highly reactive free radicals as byproducts of metabolism, which would then be prone to damage essential molecules such as DNA, was absolutely seminal: Arguably it was the first time that anyone had truly identified a plausible biochemical mechanism for the life-long accumulation of damage that eventually causes physiological decline and death. But Denham was not alone in thinking along these lines in the mid-1950s, and it is pretty much certain that if he had not proposed this when he did, others would have done so within a year or three— notwithstanding the fact that very few other gerontologists of the time knew (or felt the need to know) enough chemistry even to understand the idea for many years thereafter. It was a very different story 18 years later, when Denham published a virtually unnoticed article2 suggesting that mitochondria, and specifically mitochondrial DNA, might be the major locus of free radical damage leading to aging. This insight was followed up by virtually no one until it was revived3 (without attribution) in 1989, following which it became one of the dominant themes in biogerontology (and, incidentally, my own major area of interest when I entered the field in the mid-1990s). Had Denham been less far ahead of his time, and been able to bring his new idea to the attention and interest of more of his colleagues, progress in our field might have been a good deal faster. There is also another aspect of Denham’s 1972 paper that merits our attention. Far too often in science, including biogerontology, a researcher rises to prominence on the
back of a single important contribution and then spends the rest of his or her career defending it with a level of vehemence not wholly justified by available data. Denham did not make that mistake. His own experiments on the impact of dietary anti-oxidants on rodent longevity were overall rather underwhelming. A lesser scientist in that predicament might have swept this under the carpet and bashed on regardless, or else gone too far the other way and abandoned the theory wholesale, as some are inclined to do with the entire free radical theory nowadays. Denham, instead, accepted the need to reconcile the data that originally inspired the theory with the results he was obtaining, and he didn’t shrink from that quest until he had found a solution, namely the possibility that free radicals do their damage in a compartment to which anti-oxidants lack access. It should be particularly borne in mind that 1972 was only a few years after mitochondria had been shown4 to contain DNA at all, and moreover that that discovery was not made by gerontologists. As such, this is a sterling example of the value of exploring beyond one’s core area of interest and expertise and thereby encouraging cross-disciplinary ideas to emerge, a dictum that I have followed assiduously throughout my career and which unequivocally underpins most of my key contributions. Denham’s status as one of the very few people whom I not only admire but elevate to the status of role model arises not only from his science, however, but also from his community leadership. One reason why he was such a voice in the wilderness in 1972 was that he was in, well, the wilderness, having recently deserted the Gerontological Society of America (GSA), and founded a new organization, the American Aging Association (AGE). Why did he do this? One shortcoming that the GSA had, and indeed has to this day, is that biology is a very minor component of its activities and its meetings, hugely overshadowed by the hordes of clinicians, sociologists, and policy experts who form the Society’s other sections; AGE, by contrast, was from the outset dedicated solely to the biology of aging. But perhaps more importantly, 1970 was a time when biogerontology
SENS Research Foundation, Mountain View, California.
479
Rejuvenation Research 2014.17:479-480. Downloaded from online.liebertpub.com by Uc Davis Libraries University of California Davis on 02/06/15. For personal use only.
480
was becoming increasingly ‘‘politically correct’’ as efforts grew to elevate its prestige in the corridors of power, and to a great extent that meant distancing itself from the quest to actually do something about aging. In short, the indisputably daunting complexity of aging and the lack of a coherent biomedical research path to postponing it had led to a fear that the discussion of such matters, as however long-term a goal, risked bringing the field into disrepute. Harman was one of very few prominent members of the field who dissented from this, and arguably the one who did the most— and sacrificed the most in terms of his standing—in his efforts to counteract it. AGE was for many years shunned by many in the field, and only in the late 1990s did it truly begin to rival the GSA, but by now it has become generally recognized as unsurpassed in its scientific quality—and it has done so without ever drawing back from its interventionfocused roots. Moreover, Denham took this campaign global in 1985 by forming the International Association of Biomedical Gerontology, a conference series whose 10th iteration I was privileged to take on, allowing me to launch the ongoing series of Cambridge SENS meetings, an achievement that I rate among my proudest. In conclusion, let me just say that as a gerontologist who is first and foremost driven by the humanitarian quest to free us all of the tyranny of aging, I can think of no forerunner
DE GREY
whose example is more clearly one to follow than Denham Harman. If, by my scientific and outreach contributions, I have inspired a new army of talented younger individuals to join this crusade, it is substantially by emulating the ways in which Denham inspired me. He will not be forgotten. References
1. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol 1956;11:298–300. 2. Harman D. The biologic clock: The mitochondria? J Am Geriatr Soc 1972;20:145–147. 3. Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet 1989;1:642–645. 4. Nass S, Nass MMK. An electron histochemical study of mitochondrial fibrous inclusions. J R Microsc Soc 1963;81: 209–213.
Address correspondence to: Aubrey D.N.J. de Grey SENS Research Foundation 110 Pioneer Way Mountain View, CA 94041 E-mail: [email protected]
