Long for This World: The Strange Science of Immortality - Jonathan Weiner (2010)

Notes on Sources and Further Reading

“The subject is really an enormous subject,” William James wrote in 1898, in his essay “Human Immortality.” “At the back of Mr. Alger’s Critical History of the Doctrine of a Future Life there is a bibliography of more than five thousand titles of books in which it is treated.”

On top of that enormous subject, we now have the modern science of longevity. If you search for the keyword “gerontology” in the world’s largest online index of medical literature, Medline, you get a list of more than 25,000 articles, all published since the year 1950.

Of course, longevity and immortality are not the same thing. Even if gerontologists learned to slow, stop, or even reverse the process of aging, they would not make human bodies live forever. They would eliminate only one cause of death. Nevertheless, aging is by far the most common cause of death in this vale of tears. A cure for aging would mean so many centuries or millennia of future life that the prospect looks very much like immortality from here.

Because the science of longevity is so young and turbulent, it’s too soon for critical histories and giant bibliographies. Here are a few notes on some of my sources, chapter by chapter, with suggestions for further reading.

CHAPTER 1: IMMORTAL LONGINGS

In the last decade or so, as their field has heated up, gerontologists have published a whole shelf of books for a general audience. These include:

Austad, S. N. (1999). Why We Age: What Science Is Discovering About the Body’s Journey Through Life. Wiley.

Butler, R. N. (2008). The Longevity Revolution: The Benefits and Challenges of Living a Long Life. PublicAffairs.

Carnes, B. A., and S. J. Olshansky (2002). The Quest for Immortality: Science at the Frontiers of Aging. Norton.

Guarente, L. (2002). Ageless Quest: One Scientist’s Search for the Genes That Prolong Youth. Cold Spring Harbor Laboratory Press.

Hayflick, L. (1994). How and Why We Age. Ballantine.

Kirkwood, T. (1999). Time of Our Lives: The Science of Human Aging. Oxford University Press.

Rose, M. R. (2005). The Long Tomorrow: How Advances in Evolutionary Biology Can Help Us Postpone Aging. Oxford University Press.

West, M. (2003). The Immortal Cell: One Scientist’s Quest to Solve the Mystery of Human Aging. Doubleday.

Aubrey de Grey has published a book about his “Strategies for Negligible Senescence”:

de Grey, A. D. N. J., with Michael Rae (2007). Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. St. Martin’s.

Aubrey de Grey has also published almost one hundred manifestos and scientific articles on the subject. For one of the early, provocative papers in which he rode out to battle against most gerontologists, see de Grey, A. D., B. N. Ames, et al. (2002). “Time to talk SENS: Critiquing the immutability of human aging.” Ann N Y Acad Sci 959: 452–62; discussion 463–65. As de Grey and his coauthors write, “Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus accumulates.” Finding ways to remove the accumulating damage, they argue, “would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely…. Such ways exist in all cases, implying that indefinite postponement of aging—which we term ‘engineered negligible senescence’—may be within sight.”

See also:

de Grey, A. D., J. W. Baynes, et al. (2002). “Is human aging still mysterious enough to be left only to scientists?” Bioessays 24(7): 667–76.

de Grey, A. D. (2003). “An engineer’s approach to the development of real anti-aging medicine.” Sci Aging Knowledge Environ 2003(1): VP1.

de Grey, A. D. (2004). “Biogerontologists’ duty to discuss timescales publicly.” Ann N Y Acad Sci 1019: 542–45.

de Grey, A. D. “Resistance to debate on how to postpone ageing is delaying progress and costing lives.” EMBO Rep 2005; 6:S49–S53.

For an angry counterattack by gerontologists, see:

Warner, H., J. Anderson, et al. (2005). “Science fact and the SENS agenda: What can we reasonably expect from ageing research?” EMBO Rep: 26:1006–8.

For de Grey’s defense, see these papers, and their references: de Grey, A. D. (2006). “Is SENS a farrago?” Rejuvenation Res 9(4): 436–39; de Grey, A. D. (2006). “SENS survives the challenge: Now let’s get to work.” Rejuvenation Res 9(4): 429–30.

Among dozens of recent technical reviews of current gerontology, I found this one particularly useful as a balanced guide to the literature: Vijg, J., and J. Campisi (2008). “Puzzles, promises and a cure for ageing.” Nature454(7208): 1065–71. Vijg and Campisi survey recent discoveries in the science of aging, which seem to show that the life span of yeast, worms, flies, and mice “is plastic and can be manipulated.” The authors caution that we need to understand those studies much more deeply “before we can evaluate if abrogation of human senescence is a realistic prospect.”

On the history of human longevity, I found these books helpful, among others:

Riley, J. C. (2001). Rising Life Expectancy: A Global History. Cambridge University Press.

Anderson, M. (1996). British Population History. Cambridge University Press.

The owners of the Eagle are justly proud of its history, and there are many plaques in the pub. John Chainey’s notes on the RAF graffiti are detailed and extensive.

I also consulted a few books about the town’s history, including:

Darby, H. C. (1977). Medieval Cambridgeshire. Oleander.

Cobban, A. B. (1988). The Medieval English Universities: Oxford and Cambridge to circa 1500. Scholar.

Blair, J. (1984). The Anglo-Saxon Age: A Very Short Introduction. Oxford University Press.

CHAPTER 2: THE PROBLEM OF MORTALITY

These are two good panoramic surveys of the subject’s history:

Gruman, G. J. (1966). A History of Ideas About the Prolongation of Life. Springer.

Hancock, D. B. (2009). Mortal Coil: A Short History of Living Longer. Yale University Press.

For a wise short review, read:

Shapin, S., and C. Martyn (2000). “How to live forever: Lessons of history.” BMJ 321: 1580–82.

An excellent book about Gilgamesh:

Damrosch, D. (2007). The Buried Book: The Loss and Rediscovery of the Great Epic of Gilgamesh. Holt.

On Steinach:

Wyndham, D. (2003). “Versemaking and lovemaking—W. B. Yeats’ ‘Strange Second Puberty’: Norman Haire and the Steinach rejuvenation operation.” Journal of History of the Behavioral Sciences 39(1): 25–50.

I’ve mentioned only a few twentieth-century immortalists in this chapter. If you dig down into any decade, you can find a dozen now forgotten doctors and biologists who hoped to live forever. A few months ago I found an old, slightly pulpy, but entertaining paperback: McGrady, P. M., Jr. (1968). The Youth Doctors. Ace. It is full of names of lost immortalists, including one rebel whose polemics have at least a family resemblance to Aubrey de Grey’s.

See also Comfort, A. The Process of Ageing (1964). Signet Science Library. Dated, but still good reading.

Another readable paperback from that time, also with yellowing pages:

Harrington, A. (1969). The Immortalist: An Approach to the Engineering of Man’s Divinity. Avon. It begins, “Death is an imposition on the human race, and no longer acceptable.”

CHAPTER 3: LIFE AND DEATH OF A CELL

Here are a few books about the beauty of the beginning of the life cycle:

Bonner, J. T. (1993). Life Cycles: Reflections of an Evolutionary Biologist. Princeton University Press. John Tyler Bonner, born in 1920 and still going strong, is one of the best biologist-writers alive. This is a delightful book about the evolution of the life cycle, and the evolution of Bonner.

Gilbert, S. F. (2006). Developmental Biology. Sinauer. The standard textbook.

Wolpert, L. (1991). The Triumph of the Embryo. Oxford University Press.

On the evolution of multicellular life:

Bonner, J. T. (2000). First Signals: The Evolution of Multicellular Development. Princeton University Press.

Buss, L. W. (1987). The Evolution of Individuality. Princeton University Press. A bit old, and difficult, but fascinating.

This monumental work of scholarship helped bring new life to the science of gerontology:

Finch, C. E. (1990). Longevity, Senescence, and the Genome. University of Chicago Press.

On the hydra:

Martinez, D. E. (1998). “Mortality patterns suggest lack of senescence in hydra.” Exp Gerontol 33: 217–25.

Maria Rudzinska was working in a long tradition at Rockefeller University. Not only was Alex Carrel there before her, so was another early eminence there, Jacques Loeb. See, for instance:

Loeb, J., and J. H. Northrup (1917). “On the influence of food and temperature upon the duration of life.” Biological Chem. 32: 103–21.

Two of Rudzinska’s papers on her beloved Tokophrya:

Rudzinska, M. A. (1951). “The influence of amount of food on the reproduction rate and longevity of a suctorian (Tokophrya infusionum).” Science 113: 10–11.

Rudzinska, M. A. (1984). “Cellular and clonal aging in the suctorian protozoan Tokophrya infusionum.” S. J. Karakashian, H. N. Lanners, and M. A. Rudzinska. Mech. Ageing Develop. 26: 217–29.

CHAPTER 4: INTO THE NEST OF THE PHOENIX

A wonderful and authoritative collection of old Jewish legends: The Book of Legends, Sefer Ha-Aggadah: Legends from the Talmud and Midrash (1999). H. N. Bialik, editor; W. Braude, translator. Schocken.

For reviews of Denham Harman’s thinking about aging, see:

Harman, D. (2006). “Free radical theory of aging: an update,” Ann NY Acad Sci 1067: 10–21.

Kitani, K., and G. O. Ivy (2003). “‘I thought, thought, thought for four months in vain and suddenly the idea came.’ Interview with Denham and Helen Harman.” Biogerontology 4: 401–12.

de Grey, A. D. (1997). “A proposed refinement of the mitochondrial free radical theory of aging.” Bioessays 19(2): 161–66.

de Grey, A. D. (2002). “Three detailed hypotheses implicating oxidative damage to mitochondria as a major driving force in homeotherm aging.” Eur J Biochem 269(8): 1995.

CHAPTER 5: THE EVOLUTION OF AGING

Peter Medawar’s key essays about the evolution of aging are reprinted in:

Medawar, P. (1981). The Uniqueness of the Individual. Dover.

He returns to the subject in his quirky autobiography:

Medawar, P. (1988). Memoir of a Thinking Radish. Oxford University Press.

And again in:

Medawar, P. (1990). The Threat and the Glory. HarperCollins.

See also:

Finch, C. E., and E. M. Crimmins (2004). “Inflammatory exposure and historical changes in human life-spans.” Science 305(5691): 1736–39.

Caspari, R., and Lee, S.-H. (2004). “Older age becomes common late in human evolution.” PNAS 101(30): 10895–10900.

Crespi, B. J. (2004). “Vicious circles: Positive feedback in major evolutionary and ecological transitions.” TREE 19(12): 627–33.

Rose, M. R. (1991). Evolutionary Biology of Aging. Oxford University Press.

Stearns, S. C., and J. C. Koella (2008). Evolution in Health and Disease. Oxford University Press.

Platt, R. (1963). “Reflections on ageing and death.” Lancet. 281: 1–6.

CHAPTER 6: THE GARBAGE CATASTROPHE

Holliday, R. (2006). “Aging is no longer an unsolved problem in biology.” Ann NY Acad Sci 1067: 1–9.

de Grey, A. D. (2007). “Alzheimer’s, atherosclerosis, and aggregates: A role for bacterial degradation.” Nutr Rev 65(12 Pt 2): S221–27.

Terman, A., and U. T. Brunk (2006). “Oxidative stress, accumulation of biological ‘garbage,’ and aging.” Antioxid Redox Signal 8(1–2): 197–204.

Stroikin, Y., H. Dalen, et al. (2005). “Testing the ‘garbage’ accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy.” Biogerontology 6(1): 39–47.

CHAPTER 7: THE SEVEN DEADLY THINGS

For a full-length treatment of de Grey’s Strategies for the Engineering of Negligible Senescence, see his book Ending Aging (op cit.).

He’s also published dozens of shorter accounts, including:

de Grey, A. D. (2005). “A strategy for postponing aging indefinitely.” Stud Health Technol Inform 118: 209–19.

For Michael Hecht’s experiments with beta-amyloid:

Kim, W., Y. Kim, et al. (2006). “A high-throughput screen for compounds that inhibit aggregation of the Alzheimer’s peptide.” ACS Chem Biol 1(7): 461–69.

Kim, W., and M. H. Hecht (2008). “Mutations enhance the aggregation propensity of the Alzheimer’s A beta peptide.” J Mol Biol 377(2): 565–74.

de Grey, A. D., P. J. Alvarez, et al. (2005). “Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases.” Ageing Res Rev 4(3): 315–38.

CHAPTER 8: THE METHUSELAH WARS

For a meticulously detailed contemporary history, see Hall, S. (2003). Merchants of Immortality: Chasing the Dream of Human Life Extension. Houghton Mifflin.

Klass, M. R. (1983). “A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results.” Mech Ageing Dev 22(3–4): 279–86.

Klass, M., and D. Hirsh (1976). “Non-ageing developmental variant of Caenorhabditis elegans.” Nature 260(5551): 523–25.

Kenyon, C., J. Chang, et al. (1993). “A C. elegans mutant that lives twice as long as wild type.” Nature 366(6454): 461–64.

Kenyon, C. (2005). “The Plasticity of Aging: Insights from Long-Lived Mutants.” Cell 120: 449–60.

Song, S., and T. Finkel (2007). “GAPDH and the search for alternative energy.” Nature Cell Biology 9(8): 869–70.

Zhang C., and A. M. Cuervo (2008). “Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function.” Nat Med 14(9): 959–65.

Kaushik S., and A. M. Cuervo (2008). “Chaperone-mediated autophagy.” Methods Mol Biol 445:227–44.

Cuervo, A. M. (2008). “Autophagy and aging: Keeping that old broom working.” Trends Genet 24: 604–12.

Cuervo, A. M., L. Stefanis, et al. (2004). “Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy.” Science 305: 1292–95.

Mizushima N., B. Levine, et al. (2008). “Autophagy fights disease through cellular self-digestion.” Nature 451:1069–75.

Hansen, M., A. Chandra, et al. (2008). “A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.” PLoS Genet 4(2): e24.

Rubinsztein, D. C., J. E. Gestwicki, et al. (2007). “Potential therapeutic applications of autophagy.” Nat Rev Drug Discov 6(4): 304–12.

Sarkar, S., E. O. Perlstein, et al. (2007). “Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models.” Nat Chem Biol 3(6): 331–38.

Sarkar, S., B. Ravikumar, et al. (2009). “Autophagic clearance of aggregate-prone proteins associated with neurodegeneration.” Methods Enzymol 453: 83–110.

CHAPTER 9: THE WEAKEST LINK

Aubrey de Grey introduced his cancer cure in these papers:

de Grey, A. D. (2005). “Whole-body interdiction of lengthening of telomeres: a proposal for cancer prevention.” Front Biosci 10: 2420–29.

de Grey, A. D., F. C. Campbell, et al. (2004). “Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers.” Ann N Y Acad Sci 1019: 147–70.

De Grey writes about his hopes for the Singularity in Edge.com, January 2, 2009. http://ieet.org/index.php/IEEET/more/2781.

See also de Grey, A. D. (2009). “The singularity and the Methuselarity: Similarities and differences.” Stud Health Technol Inform 149: 195–202. Here he writes, “Aging, being a composite of innumerable types of molecular and cellular decay, will be defeated incrementally. I have for some time predicted that this succession of advances will feature a threshold, which I here christen the ‘Methuselarity….’” As he says, that threshold is very close to the Singularity.

For a massive defense of the Singularity idea, see Kurzweil, R. (2005). The Singularity Is Near: When Humans Transcend Biology. Viking.

CHAPTER 10: LONG FOR THIS WORLD

For an excellent collection of papers on aspects of the great questions “can we” and “should we,” see:

Post, S. G., and R. H. Binstock, eds. (2004). The Fountain of Youth: Cultural, Scientific, and Ethical Perspectives on a Biomedical Goal. Oxford University Press.

For John Cheever’s envy of Saul Bellow’s immortality, see Atlas, J. (2000). Bellow: A Biography. Random House.

Updike’s last book of poems is one of his finest: Endpoint and Other Poems (2009). Alfred A. Knopf.

Because life expectancy has lengthened within the lifetimes of baby boomers, they may find the approach of old age even more disturbing, in some ways, than generations past. What if their ship is sinking within sight of land? Shakespeare speaks of the “double death”: “’Tis double death to drown in ken of shore.”

For an insightful essay on baby boomers’ competition for more years, see Kinsley, M. (2008). “Mine is longer than yours.” New Yorker (April 7).

On the psychology of time—our own private expectations of how much or little time lies ahead—see Carstensen, L. L. (2006). “The influence of a sense of time on human development.” Science 312(5782): 1913–15.

There is a large and growing literature on twenty-first-century demography. In this chapter, I cite Christensen, K., G. Doblhammer, et al. (2009). “Ageing populations: the challenges ahead.” Lancet 374(9696): 1196–208. Christensen, K., A. M. Herskind, et al. (2006). “Why Danes are smug: comparative study of life satisfaction in the European Union.” Bmj 333(7582): 1289–91.

For Aubrey de Grey’s rejection of demographers’ forecasts:

de Grey, A. D. (2006). “Extrapolaholics anonymous: Why demographers’ rejections of a huge rise in cohort life expectancy in this century are overconfident.” Ann N Y Acad Sci 1067: 83–93.

Terman, A., and U. T. Brunk (2005). “Is aging the price for memory?” Biogerontology 6:205–10.

CHAPTER 11: THE TROUBLE WITH IMMORTALITY

For the story of Luz, I consulted The Book of Legends, Bialik and Braude (op cit.).

This book is still worth reading, although it is dated by its conviction that Freud and his disciples had us figured out: Becker, E. (1973). The Denial of Death. Free Press.

For a wonderful new book exploring some of the same emotional territory, read Barnes, J. (2008). Nothing to Be Frightened Of. Alfred A. Knopf.

Veatch, R. M. (2009). “The evolution of death and dying controversies.” Hastings Center Report 39(3): 16–19.

Haeckel, E. (1900). The Riddle of the Universe. Harper & Brothers.

imageapek, K. (1925). The Makropulos Secret. International Pocket Library.

Bernard Williams’s paper about imageapek’s play is reprinted here:

Williams, B. (1973). Problems of the Self. Cambridge University Press.

Someday soon, neurophilosophers may be able to explore Joshua Lederberg’s point about remembering and forgetting. See, for instance:

Shuai, Y., B. Lu, et al. (2010). “Forgetting is regulated through Rac activity in Drosophila.” Cell 140(4): 579–89.

And see Bhanoo, S. N. (2010). “Forgetting, with a purpose.” New York Times.

If we ever do stop aging, what will become of the wisdom of the ages? Everything ever written about childhood, youth, middle and old age will seem incredibly dated. For the time being, at least, this is still a valuable anthology:

Sampson, A., and S. Sampson (1985). The Oxford Book of Ages. Oxford University Press.

CHAPTER 12: THE EVERLASTING YES AND NO

Robert Butler writes about the “longevity dividend” in his book The Longevity Revolution (op cit.). See also Butler, R. N., R. A. Miller, et al. (2008). “New model of health promotion and disease prevention for the 21st century.” BMJ 337: a399.

Two attacks from the center against the fringes of antiaging medicine:

Olshansky, S. J., L. Hayflick, et al. (2002). “Position statement on human aging.” J Gerontol A Biol Sci Med Sci 57(8): B292–97.

Olshansky, S. J., L. Hayflick, et al. (2002). “No truth to the fountain of youth.” Sci Am 286(6): 92–95.

Vijg, J. (2007). Aging of the Genome: The Dual Role of DNA in Life and Death. Oxford University Press.

Houellebecq, M. (2001). The Elementary Particles. New York, Vintage.

Graham, A. C., trans. (2008). Poems of the Late T’ang. NYRB Classics.

William Butler Yeats composed beautiful translations of the Upanishads. Yeats, W. B., and Swami Shree, trans. (1975). The Ten Principal Upanishads. Macmillan.