The Pursuit of Longevity - David Ewing Duncan

Link: http://www.acumenjournal.com/
Date: 09-12-03
Author: David Ewing Duncan
Source: Acumen Magazine
Title: The Pursuit of Longevity
Comment: In keeping with the discussion we are having on Sunday with Betterhumans staff and also with the Web Focus post of Laz, here's an article from the nascent magazine Acumen, of which I am a charter member. Please feel free to borrow my copy of the text to read and bring your views to the discussion.

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The Pursuit of Longevity

Long-lived worms tantalize researchers with the promise of extended life. In the meantime, though, they suggest cures for chronic diseases of old age.

DAVID EWING DUNCAN


In the University of California at San Francisco’s new, silver-skinned lab complex at Mission Bay, Cynthia Kenyon, Ph.D., shows me a video that she frequently parades in front of investors, journalists, and PBS audiences: millimeter-long worms bioengineered to live more than twice as long as usual. In 1993, Dr. Kenyon, a molecular geneticist at UCSF, made global headlines when her lab discovered that the suppression of a single gene, DAF-2, could extend a nematode’s life span. A key component in the genetic pathway that regulates endocrine signaling and resistance to oxidative stress (that is to say, the damage done when cells use oxygen in metabolism) the natural silencing of DAF-2 triggers a kind of slowing down in worm larvae during times of extreme environmental pressure (for instance, a lack of food), allowing the larvae to survive. When Dr. Kenyon suppressed DAF-2 in adult worms, they lived 45 days instead of the usual 18 days—and they remained vigorous and healthy until close to the end.

Dr. Kenyon’s finding shocked biologists, who had long assumed that something as complex as aging couldn’t be affected by a single gene, even in nematodes. Hundreds, possibly thousands, of human genes are known to contribute to aging, influencing everything from baldness to dementia. Yet I see the evidence on Dr. Kenyon’s video monitor: a normal, 3-day-old worm in the prime of life, a Caenorhabditis elegans (whose simple genetics and cell structure make it a favorite of geneticists) is wriggling in a broth of nutritious bacteria. At 13 days, the worm is sluggish, its head barely stirring as death approaches. The next images are of a mutant worm, with the knocked-down DAF-2 gene, which at 25 days is still squirming away.

“This video says more than 20 Nature articles [can say],” says Dr. Kenyon, a thin, youthful 49 year old. What she tells me next is harder to accept: her mutant worms and other recent breakthroughs in antiaging, might hold the key to extending life in far more complex organisms—even in humans. “Worms are worms, and humans are humans,” she says, “but I see no reason yet why this shouldn’t work in people.”

Once a moribund field out on the fringe, antiaging science has witnessed an impressive list of discoveries since Dr. Kenyon’s DAF-2 research appeared in Nature a decade ago.1 The most enthusiastic researchers contend that the days of normal aging in humans may be numbered. Most interesting, they argue that people will not age like Tiresias—that is, by enduring a wizened old age. They believe that the manipulation of genes like DAF-2 and other age-retarding remedies will extend youth in humans, as it has for worms, flies, and mice. At the least, the research could lead to ways to put off or eliminate age-related diseases like Alzheimer’s and many cancers.

Link to Article

Thanks for hosting the article... and your formatting of reference information at the top of the post.. is something we should all probably work toward. This is certainly germane to our upcoming discussion.

Link: http://www.acumenjournal.com
Date: 09-12-03
Author: Philip Ross
Source: Acumen Journal of Science
Title: Designed to Live
Comment: Tom Kirkwood argues against the popular notion of programmed death and how to reconcile reproduction and survival. Here's an excellent article that will help us in our discussion and study of the principles of ageing and life-extension on Sunday as well. If you so wish, please feel free to read my copy available at the link provided for your own research.

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Designed to Live

Tom Kirkwood took up the evolutionary explanation of aging in part to fight what he says is gerontology’s greatest misconception: that we are programmed to die.

PHILIP ROSS

Photography by Keri Pickett

One February night in 1977, Tom Kirkwood, then only 25, was struck by the biggest insight of his life—“my ‘Eureka!’ moment,” he calls it. Like Archimedes, it hit him while he was in the bath.

Dr. Kirkwood—who holds a doctorate in biology and is head of gerontology at the University of Newcastle upon Tyne—had grasped the implications of a forced trade-off between the two most important things in life: sex and death. He had come upon it after contemplating the way aging might manifest itself in the two basic kinds of cells—those of the body (or soma, in Greek) and those of reproduction (the germline). Energy lavished on one, he realized, must come at the expense of the other, yet only the reproductive cells need to resist the ravages of age. Genetically, the body is as disposable as a snake’s skin.

For how long, then, will you need your body? Only so long as you might reasonably expect to survive the slings and arrows—and fangs, famines, and acute illnesses—that decimated our ancestors in the Stone Age, when our genetic heritage was forged. Very few of those ancestors lived past 60; most died much earlier.

This scientific theory contrasts sharply with the competing popular notion of programmed death, which holds that the body self-destructs in the service of some higher good, like fending off cancer or clearing the field for the next generation. It also allows scientists to make certain predictions, some of which Dr. Kirkwood and his collaborators have confirmed.

They studied the life histories of tens of thousands of British aristocrats and found that those who lived the longest tended to have the smallest families. They bred fruit flies for longevity over a period of many generations and found that the resulting Methuselah flies were less prolific than their wild cousins. They also cite the better-known case of eunuchs, who outlive other men, and of geldings (like Funny Cide, this season’s equine star), which may race long past the age at which stallions are often put out to pasture.

Perhaps the most critical implication of the theory, that aging mechanisms must involve the self-maintenance of somatic cells, has been vindicated by several experiments. In one, skin cells taken from long-lived species did much better under oxidative stress from bleach and other chemicals, than did those from shorter-lived species.

Link to Article

Link: http://www.acumenjournal.com
Date: 09-12-03
Author: Christopher Scott
Source: Acument Journal of Sciences
Title: Ethical Dilemma
Comment: The bioethics of life-extension will be certainly a subject we will talk about in our upcoming discussion. Ethics in biology in general will be a hotly debated issue in the coming years ahead with the new powers we are acquiring through new technology for modification of what it means to be human. Please feel free to read my copy of this article for your own education and research into these globally vital issues.

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Ethical Dilemma

When solutions to biological quandaries stem from moral certitudes instead of give-and-take debate, public discourse suffers.

CHRISTOPHER SCOTT

On a bitterly cold January morning in Washington, D.C., the ninth meeting of the President’s Council on Bioethics comes to order. Presiding is the council’s chairman, Leon Kass, M.D., Ph.D., on sabbatical from his faculty position at the University of Chicago. After acknowledging the designated federal officer whose presence is required to legitimize the meeting, Dr. Kass sets the agenda for the day. It includes discussion of two documents: a council working paper on the ethical aspects of controlling the sex of children and a draft of a paper written by Dr. Kass on the perils of biotechnology’s march toward improving human health. Leading the agenda is a presentation on the biology of human embryonic development by John Marius Opitz, M.D., a professor of pediatrics, genetics, and obstetrics at the University of Utah.

Those giving expert testimony before a presidential council are carefully chosen, and Dr. Opitz is no exception. The avuncular 68-year-old is an internationally recognized authority on human genetics, having been among the first physician-scientists to correlate groupings of developmental anomalies with heredity. His name is associated with the understanding of no fewer than ten genetic syndromes, including pseudohermaphroditism, severe dwarfism, and retardation. For nearly 30 years, he has served as the editor of the peer-reviewed Journal of Medical Genetics. Before introducing Dr. Opitz, Dr. Kass instructs the council that the lecture is central to their deliberations on the moral status of the human embryo, which he calls “this entity”:

“ [W]e . . . owe it to ourselves, and, again, to those who would read what we write, to . . . speak as accurately and as fully as we can about this entity . . . whose true nature is so much in dispute and which is, in fact, somewhat mysterious.

. . . I remind you that the house rules this morning are that we are going to try to learn what we can about the biology. Certain kinds of biophilosophical questions might be in order, but I will try and preside in order to keep this from turning into an opportunity to score some points in the moral debate about the so-called moral status of embryonic life.”1


Both the upcoming biology lesson and the instruction against scoring moral points would seem to be necessary. Of the 12 council members present, in addition to Dr. Kass, all are well-known ethicists or policy advisers, but only 5 have any medical training at all. Among the full council of 17, only University of California, San Francisco’s Elizabeth Blackburn, a biomedical Ph.D., can lay claim to expertise in cell biology, a discipline closely related to Dr. Opitz’s field.

Dr. Opitz begins his presentation by formulating working definitions of life and development. He places sexual reproduction within the context of an organism’s life cycle, before moving on to illustrations of sexual reproduction, fertilization, meiosis, and the conventional stages of human development—familiar images to anyone who recalls high school biology. Then he reaches the central topic of his research career: what happens when genetically regulated developmental pathways go wrong. These are the inborn errors that lead to malformation, dysfunction, or death. The slides come and go with merciful quickness: a picture of a Japanese child with Down syndrome; a child with Turner syndrome, missing a sex chromosome; one with Potter syndrome, missing the kidneys; the profound defects of Siamese twinning; children missing spinal cords, brains, and vital organs; and finally, fetuses so deformed they are not recognizable as human. Dr. Opitz points out that many of these biological wrong turns occur during the natural development of the blastula, the tiny ball of cells that later becomes the human fetus. He believes that in vitro fertilization, a procedure for infertile couples involving an implanted blastula, if performed thousands of times over, may increase the likelihood of certain developmental abnormalities.

Dr. Kass, in spite of his stated intention of not letting the meeting become a “moral debate about the so-called moral status of embryonic life,” allows the following interchange between commission member William Hurlbut, M.D., conservative theologian and professor of human biology at Stanford University, and Dr. Opitz:

Hurlbut: We’ve had to struggle with this question of when there is intrinsic moral value in this developing entity . . . I want to ask you your feeling about the moral meaning . . . in which before, say, 14 days, there is something of different moral meaning than at 14 days.

Opitz: I don’t mean to be a moral coward here, or sidestep that issue, by not . . . expressing my moral feelings about the subject, which I think is slightly beside the point. Because I have a strong suspicion that everybody in this room has their own moral feelings and opinions on the subject.2

Perhaps no one in the room holds a stronger opinion than the nation’s most influential bioethicist, Dr. Kass. He does not scruple to violate the rule of procedure about the moral dangers of cloning humans for reproductive purposes. In his own view, he has a mission.

Link to Article

Link: http://www.acumenjournal.com
Date: 09-12-03
Author: Sherwin B. Nuland
Source: Acumen Journal of Sciences
Title: How to Grow Old
Comment: From the quote below, we can see that Mr. Nuland believes that the quite arguable 'maximum' lifespan our species is capable of should not be increased and instead subscribes to the idea of 'compressed morbidity' or trying to cram all the suffering of old age into as small a space of time as possbile before doing our evolutionary duty and shuttling off only to be replaced by some new and improved version. As with the other articles I have provided links for, please feel free to read my copy so that we may all benefit from his wisdom through discussion and education.

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How to Grow Old

A physician’s prescription for aging.

SHERWIN B. NULAND

Aging is not a disease. It is the condition upon which we have been given life. The aging and eventual death of each of us is as important to the ecosystem of our planet as the changing of the seasons. When William Haseltine, Ph.D., the brilliant biotechnology entrepreneur who is the CEO of Human Genome Sciences, says, “I believe our generation is the first to be able to map a possible route to individual immortality,” we should cringe with distaste and even fear, not only at the hubris of such a statement but also at the danger it poses to the very concept of what it means to be human. The current biomedical campaign against the natural process of aging is but part of a much larger conception of humankind’s future, in which it is thought by some that parents may one day order up the IQ, complexion, and stature of their intended offspring by manipulating their DNA.

These are not the problems American medicine should be struggling with. Its proper task is not the prolongation of life beyond the naturally decreed maximum span of our species (which seems to be in the neighborhood of 120 years), but its betterment. And if anyone’s life needs betterment it is surely the elderly man or woman still living well beyond the years of vigor and productivity because the benisons of public health and biomedicine have made it possible. The percentage of the aged in our population increases with every passing year, and far too many of these people are doddering. The very gradual increase in life expectancy of previous generations has been replaced by a surge forward: the 20th century saw a 33-year gain, an astonishing figure compared to any comparable period in history. Until these recent changes, population size had the general configuration of a pyramid with a wide base of children, the top narrowing with age. It has now taken on somewhat the shape of a rectangle, as more aged individuals reach the upper levels. As disease treatment continues to improve and public health measures reach a larger segment of the population, this trend will only increase.

Link to Article


About The Author:



Sherwin (Shep) Nuland is the author of the National Book Award winning How We Die: Reflections on Life's Final Chapter. He has also written The Wisdom of the Body, The Origins of Anesthesia, Doctors: The Biography of Medicine, Medicine: The Art of Healing, The Mysteries Within and Leonardo da Vinci. He is a clinical professor of surgery at Yale where he teaches bioethics and medical history. Besides being a regular contributor to medical journals he has also written for The New York Times, The New Yorker, The New Republic, The New York Review of Books and Time. Sherwin Nuland also writes "The Uncertain Art," a regular column for The American Scholar. His newest book is Lost In America: A Journey with My Father. Shep Nuland lives in Connecticut with his family and is working on a biography of Moses Maimonides. Reference

Ive read a Nuland-Interview in an old "Stern" Issue (97').
He talked about narzism in the western community, the benefits of mortality and that we will, if we manage to extend human life, reach something like a frontier of knowledge (after 150 years).

Very funny, very useless ;-)

Sherwin B. Nuland says: " These are not the problems American medicine should be struggling with. Its proper task is not the prolongation of life beyond the naturally decreed maximum span of our species ( which seems to be in the neighborhood of 120 years ) but its betterment."

So according to Sherwin B. Nuland the proper task of American medicine is the betterment of life and not the prolongation of life beyond the naturally decreed maximum span of our species. He fails to realize that the prolongation of life beyond the naturally decreed maximum span of our species is a betterment of life. To prolong life would mean people would get old and get the diseases of aging at a higher age and probably spend a smaller percentage of their life suffering from disease. Prolonging life would give American medicine more time to find better treatments, cures and preventions for the diseases of aging so that extra time before poople need the treatments for diseases of aging means people who prolong their life beyond the decreed maximum will sufer less from the diseases of aging than people do today.

Aging is not a disease. It is the condition upon which we have been given life. The aging and eventual death of each of us is as important to the ecosystem of our planet as the changing of the seasons.

Aging is not a disease anymore than sickle cell anemia is. Sickle cell anemia renders the infected individual less vulnerable to malaria. Disease is a semantic variable based on the adaptive benefits traded. Similarly, aging is merely one strategy of evolution. Albeit a strategy that has been adopted by the vast majority of life on this planet (there are exceptions). It is nevertheless, a strategy, a pathway of least resistance for the propagation of the germline.

It is astonishingly arrogant and outright idiotic to presume that aging is a consequence of life. Furthermore it is irresponsible for a physician who is supposedly armed with intimate knowledge of biology to make such a statement when he fully well knows of many species that exhibit negligible senescence.

If I follow his metaphysical allusion that we have been "given" life, I say we earned it! We earned it through millions of years of adversity, pain and death, from the primordial to the primitive from the barbaric to the confused. From every molecule waging eternal war against the threat of entropy and chaos, to the exquisite architecture and beauty of multicellular biological systems. We humans represent the pinnacle of life in that we now stand at the precipice of being able to forever cast aside our constant companion since time immemorial, our friend and enemy, the apathetic and singularly minded, evolution. And we can do this because we are on the verge of being able to control our own genome.

Insofar as the ecosystem is concerned, the ravages that we have inflicted and continue to inflict have to do with selfishness, greed and an inherent inability to view in the long term as individuals constrained by a short lifespan. One of the immediate consequences of the prospect of an extended lifespan will be the planning, accountability and responsibility for an extended future.

When William Haseltine, Ph.D., the brilliant biotechnology entrepreneur who is the CEO of Human Genome Sciences, says, “I believe our generation is the first to be able to map a possible route to individual immortality,” we should cringe with distaste and even fear, not only at the hubris of such a statement but also at the danger it poses to the very concept of what it means to be human.

Why distaste and fear? This is something one normally associates with death and disease, not life and vitality.

What is the concept of what it means to be human anyway? Who knows it? Anyone that claims to know it is merely the holder of an opinion. If there is any such concept it would centre around how we conduct ourselves in respect to each other and our environment. One thing is for sure, we have developed enormous cognitive capacity and as a result revolutionary technology developed great power to change ourselves and our environment. Any concept of humanity should always start with, to quote a famous marvel icon, ".. with great power comes great responsibility..."

These are not the problems American medicine should be struggling with. Its proper task is not the prolongation of life beyond the naturally decreed maximum span of our species (which seems to be in the neighborhood of 120 years), but its betterment. And if anyone’s life needs betterment it is surely the elderly man or woman still living well beyond the years of vigor and productivity because the benisons of public health and biomedicine have made it possible. The percentage of the aged in our population increases with every passing year, and far too many of these people are doddering

American medicine? Since when did medicine wear a flag?

Any solution that seeks to better the aging will inevitably result in the extension of lifespan. These are the biological facts. If you seek to increase quality of life in the aging you must treat aging as a disease. He has contradicted himself here.

Naturally decreed? Here come the metaphysical allusions again. We are decreed nothing. We have what we can, what we can take and what we can make. No-one need be decreed anything except for those who allow themselves to be decreed. If we have been decreed anything it is a huge intellect without a users manual. Like child orphans cast away with no inkling of their heritage nor their potential we have been left to our devices to try to figure out our place and the meaning of existence.

If I follow his metaphysical allusion that we have been "given" life, I say we earned it! We earned it through millions of years of adversity, pain and death, from the primordial to the primitive from the barbaric to the confused. From every molecule waging eternal war against the threat of entropy and chaos, to the exquisite architecture and beauty of multicellular biological systems.

right on man thanks for your passionate response to this conservative, narrowminded sad little man. Damn straight we earned it, one only has to think of the unimaginable suffering, sorrow, and mental anguish that our bretheren before us have gone through, and continue to go through, to realize the truth of your bold statement. Maybe we'll never reach a point in time where we can say 'suffering has now been alieviated', but we can and should reduce the suffering, especially if we have a vehicle and means to do it. This isn't extropian fantasy but merciful reality, now is the time to do the humane thing and save prolong people's lives from the ravages of aging. Conservative bioethicists fear radical change and it will be their gross stupidity that could continue to harm us, the right thing to do is fight against the bioethics council and try to abolish it.

Sherwin and others like him will continue to control our futures if we let them, we simply must not let this happen...

My apologies for the broken link to the article.. Please let me know in the future if there are missing pieces that I have posted here..