Merchants of Immortality: Chasing the Dream of Human Life Extension
by: Stephen S. Hall
Topics include:
From Publishers Weekly
Drawing on scores of original interviews and contemporary source material, Hall, a contributing writer and editor at the New York Times Magazine (Invisible Frontiers: The Race to Synthesize a Human Gene), gives a timely and engrossing account of the high-stakes science of life extension. The author kicks off with the minence grise of the field, Leonard Hayflick, and his human cell line called WI-38, which opened the gates for biotech research and showed that our cells may have built-in limitations on longevity. His WI-38 strain, taken from aborted fetus cells used to develop a polio vaccine, also became an ethical flash point that, as the author shows, has steered the course of biomedical research in aging, cancer, stem cells and cloning. Here, too, are the repeated rise and fall of entrepreneur Michael West, the idiosyncratic "lapsed creationist, born-again Darwinist," who merges his spiritual belief in immortality with big money science. Hall aims to show how the Clinton administration's decision not to support therapeutic cloning and regenerative medicine represented government held hostage by "heavy-handed, ideological fundamentalism, enforced by anonymous thuggery." The book wraps with President George W. Bush's decision in 2001 to allow stem-cell research to proceed, but only using already existing cell lines. Among Hall's conclusions: distrust of science is the subtext of the debate over embryonic stem cells and research cloning, and regenerative medicine is inevitably yoked to health-care limitations in access, affordability, timeliness and, Hall writes, "simply, good medicine." He says the notion of "victory over mortality" is a canard, but we may be able to slow the aging process. This is top-drawer journalism.
Copyright 2003 Reed Business Information, Inc.
Review
"[C]ompelling . . . Merchants of Immortality is a highly readable and important book." --Shannon Brownlee
About the Author
STEPHEN S. HALL is a contributing writer at the New York Times Magazine. His pieces have also appeared in the New York Times Book Review, the Atlantic Monthly, Smithsonian, Technology Review, Science, and other periodicals. He is the author of three critically acclaimed books about contemporary science.
Prologue
The Never-Ending Life
Several years ago, while spending a
weekend in the country with my family,
I stepped out onto the porch of the
cabin where we were staying one night
and looked up into the sky. It was
unusually clear for a summer night in the
Catskills, and every familiar jot and
scrawl of the firmament was writ large
the Polestar, Little Bear, filaments of
the Milky Way strewn like pulled
cotton right down the middle of the
dome, the entire landscape "apparelled in
celestial light," as Wordsworth put it
in his "Ode: Intimations of Immortality."
A field of tall grass and wildflowers
sloped down from the porch, and
hundreds of fireflies blinked on and off
in the middle distance, so that the
line where our earthly, mortal light
yielded to the celestial became beautifully
blurred in the darkness. As I stood at
the rail, I could hear the uniquely
peaceful sound of untroubled sleep
behind me in the cabin my wife and
two children. I scanned the dark sky for
a shooting star. I even had a wish
ready.
Since I didn"t happen to see a shooting
star that night, I don"t
think it will betray any cosmic
confidences to reveal what my wish would
have been, especially since it was so
predictable. I wished for long, healthy,
productive lives for my family,
especially my children. In doing so, I
know I
was indulging a desire as ancient as our
fascination with the heavens, a
longing as timeless and fierce as the
biological instinct to protect one"s
brood. A desire so old, in fact, that it
is not only about nature, but a part of
human nature, at least for the only
species of life on earth known to be
aware of its own mortality. And as an
amateur student of aging, I also knew,
as I stood at that porch rail, that my
Darwinian warranty was about to run out.
In strictly evolutionary terms, I"d just
about outlived my biological usefulness
to the species and would not much longer
enjoy the built-in genetic
protections crafted by eons of natural
selection. Indeed, those two cherubs
sleeping inside were the agents of my
inevitable demise. Evolution protected
me long enough for me (and my wife) to
have children, but became
biologically (and, in a sense, lethally)
indifferent to us once we reached a
certain age. From paramecia to primates,
from the single-celled denizens of
pond scum to poet laureates, natural
selection stops caring about us once
we have lived long enough to reproduce.
Evolution in that sense is a strange
ship: it moves ever forward through dark
waters, keeping the species alive,
even as it throws each and every member
of the species overboard. I was
nearing fifty years of age. My primary
care physician had retired and I"d been
forced to switch to a new doctor. His
nameno jokewas Dr. Faust. And so
this midsummer night"s wish of mine,
stripped of its conflicted humility and
its faux altruism, revealed itself to be
transparently self-referential. And here
I"m tempted to add "like most of the
wishes of my generation." Because what
I was really saying was: Let us all live
a long time, we"re not quite ready
to . . . to . . . I couldn"t bring
myself to utter the D word, even in a
conversation with myself. I was content
to reiterate the ancient ritual of
submitting a time-honored petition to
indifferent gods on dark, starry nights.
In the same way, I feel that an entire
generationa generation
new to mortality, you might sayhas been
poised to file that same petition
as a kind of generational class-action
suit against the laws of nature. Many
of us have been similarly poised at the
railing of middle age, in the twilight of
something more permanent than a summer
night, launching that same
fervent petition on behalf of our
parents, our children, and, of course,
ourselves. I am speaking in part of the
baby boomers, 75 million strong in
the United States alone, as well as our
similarly entitled postWorld War II
siblings spread throughout the developed
world. This is a generation, it goes
without saying, that thinks of its
petitions as somewhat special, a
generation that is perhaps a little more
insistent about answered prayers.
Or so it appears superficially. If you
think beyond the
demographic clichs, however, it"s hard
to believe with much conviction that
the baby boomers are any more concerned
about their mortality than
previous generations and previous
cultures. Can we possibly experience
more feral emotions than the hunters and
gatherers of 10,000 years ago,
whose very mortality attached to the
success of finding their next meal? Can
we summon more urban angst than the
average citizen of ancient Rome, who
could expect to live only about twenty
or twenty-five years? Can we
honestly argue that we feel a more
exalted fear of death than the soldiers of
the greatest generation, teenage boys
like my father, huddled in foxholes,
dodging bullets? I have a hard time
convincing myself that this is so. What
makes this particular moment so unusual
in the age-old posting of these
timeless wishes is that they might
actually be answered in an altogether
different way, with altogether
unexpected consequences, in the not-too-
distant future. Perhaps I was looking in
the wrong place for my shooting
star, because in a sense the truly
meteoric agency capable of delivering on
these wishes may be found not in the
world of cosmology but biology; the
high priests of our secular age, the
molecular biologists, have begun to
address mortality in a way no group, no
generation, and no society has ever
dreamed of before.
They may not succeed, of course, and
the purpose of this book is
not to conflate promising science with
the wishful thinking of an entire
generation. It is enough to note that in
the last decade the most skilled,
ambitious, and indeed arrogant of our
sciences has lined up to tackle
the "problem" of aging (and its faithful
sidekick, death) in a way
fundamentally different from that of any
previous era of medical intervention.
This is happening at the very same time
that an enormous demographic
bulge in our population is burying
parents and picking out gray hairs in the
mirror. If nothing else, these trends
make for a fascinating convergence of
social desire and scientific ambition;
of deeply personal psychological needs
(and fears) and the shamelessly public
promissory notes that issue from the
lips of biologists, businesspeople, and
other incurable optimists; of the
inevitable decline of the human body (or
soma) and the almost alchemical,
regenerative capabilities of bland cells
in plastic dishes; of the highest
intellectual aspiration for basic
knowledge that contemporary civilization
can
muster, alongside the most common and
infinite capacity for greed and
personal advantage that has ever sullied
the name of human nature. Looking
at this intersection from one
perspective, nothing less is at stake
than a
partial or nearly total repeal of
mortality; from another perspective, we
might
be witnessing a postmodern, molecular
version of the Fountain of Youth tale,
a spectacle of promise and hubris and
failure that will make the Ponce de
Le n story look like bad summer stock.
Medicine, especially in the last
century, has consistently helped
prolong life (or, if you prefer,
forestall death), to the point where
more people
Prologue 3 in developed societies are
living to a greater age than ever before
in human history. Because we"ve done
such a spectacular job of minimizing
the agents of premature deathdiseases,
accidents, poor hygiene, injuries,
not to mention predation, starvation,
and exposurewe are living so long
that aging itself has only recently
emerged as a subdiscipline of medicine. In
a sense, we didn"t even know aging
existed as a biological phenomenon until
we started living well beyond
reproductive age, which is really all that
evolution is interested in protecting.
Now that we know aging exists as a
separate, degradative phenomenon, and
are beginning to understand it, we
naturally want to see if we can tinker
with the process. That is what we do,
and that is what I have set out here to
chronicle: an account of some of the
people who have begun to revolutionize
medicine"s assault on aging, and
the type of science they are doing.
Inevitably, my encounters have also led to
a cultural contemplation of what it
might mean to us, as individuals and as a
society, to repeal, even partially, the
laws of mortality.
For most of the recorded past, humans
could expect to live on
average about twenty years (although
that number is deceptively low
because of the high incidence of infant
and childhood mortality). A century
ago, Americans born in 1900 could expect
to live roughly forty-nine years.
Some lived longer, of course, but many
still perished at a very young age.
Civilization in the form of antiseptic
medicine, sanitation and public
hygiene, vaccination and other
measureshas dramatically increased the
amount of time we can expect to spend on
earth. Indeed, as a prominent
gerontologist, Leonard Hayflick, puts
it, "Aging is an artifact of civilization."
Some of these thoughts were on my mind
on a sunny day in December
2000, when I headed north from San
Francisco in a rented car. It was a
professional pilgrimage, in that I was
setting out to talk to Hayflick, a
scientist well known within the
biological community (indeed, almost
infamous) and yet virtually unknown
outside it. In 1961, Hayflick achieved a
rarely attained degree of academic
celebrity when he discovered that
normal human cells grown in the
laboratory have a finite lifetimethat is,
they are programmed to divide a
more-or-less fixed number of times (known
now as the "Hayflick limit") and then
simply stop replicating and senesce.
Senescence is a word groaning with
metaphoric throw weight in the context
of human gerontology; cellular
senescence begins a process of biological
lassitude and decay that ultimately
leads to cell death. Hayflick"s discovery
brought together a powerful mix of
scientific interests: aging, life span, the
biology of cells, immortality. It put
the biology of agingand therefore the
biology of life and deathsquarely in
the crosshairs of the biologist"s
microscope.
Hayflick had sent me meticulous
instructions on how to reach his
homea map marked with arrows, annotated
directions of key crossroads,
even aesthetic admonishments ("Go slow
on Highway 1 for safety and to
observe the beauty! Careful around blind
curves . . ."). As I headed north on
Highway 101 and cut across Mendocino
County toward the Pacific Ocean,
it was hard not to notice the everyday
auguries of aging and mortality that
color the way in which we view the
world, even from a car window. Outside
Guerneville, the road curved
pastdeferred to, actually a number of
towering redwoods crowding the asphalt.
Some of those massive and long-
lived creatures have lorded over this
landscape for centuries (and yet they
represent a lesson in complexity and
paradox as well as longevity, for as
Hayflick has pointed out in one of his
books, only a tiny fraction of their
cells are actually alive, the rest
inanimate pulp). At another point, within
spitting distance of the Russian River,
several birds that I took to be
buzzardshigh-shouldered, glowering
gatekeepers of the afterlife perched
on a wire, waiting, their patience
seemingly informed by the knowledge that
they never have to wait too long. Even
when you weren"t exactly looking for
them, the signs and symbols of life and
death were everywhere, just as they
are every waking day, gentle but
persistent reminders that mostly blend into
the background of our busy days.
That"s what made this a personal
pilgrimage, too. At the time, I
had just turned forty-nine and was about
to trip an important threshold on
my own actuarial odometer. My parents,
both in their seventies, were alive
and in reasonably good health. I had a
daughter who had just turned five, a
son soon to turn three. Those little
details would normally be irrelevant
intrusions in a scientific narrative; in
this one, however, they form a kind of
background matte to the portrait of
science that occupies the foreground. It is
our children, especially, whose lives
may well be altered by this new science.
Even without being crassly
self-interested, it is impossible not to
think
about the science possibly to come in
very personal terms.
In conversations with Hayflick and
other scientists over the next
few days and in subsequent months, I
heard outlined, in sketchy but
tantalizing Prologue 5 detail, a medical
future so bold in its ambitions, so
profound in its potential impact, that
if even a tenth of the promises pan out,
it will fundamentally change how we
think about life and what it means to be
human. There was talk of genes that,
when properly manipulated, might
significantly extend life span. There
was talk of stem cell therapy, a
celebrated new technology that holds the
hope of replacing aging or failing
or diseased organs and other body parts.
I even talked to several people
whose cells were being used to clone
them, in an attempt to create a short-
lived, utilitarian embryo that could be
harvested for stem cells and, perhaps,
immunologically compatible cells and
organs. In almost every instance, a
biotechnology company had been formed,
or was in the works, with dreams
of commercializing a technology that
would extend life or regenerate human
tissues and cells. Indeed, the
catchphrase of the day was "regenerative
medicine," referring to a discipline
that had its own meetings, its own
funding and supportive foundations, its
own ambitious agenda, and its own
little swarm of bioethicists and
journalists flitting around like gnats,
trying to
figure out what was going on and what it
all meant. And it was happening
very fast: on the ride to Hayflick"s
home, the news on the radio had been
dominated by the still-unresolved
Florida vote count in the 2000 presidential
election. I think it is safe to say that
no one, during those weeks of
uncertainty, could have predicted that
the new president"s first major
televised address to the nation would
focus on, of all things, embryonic stem
cells.
As I traveled around and heard these
stories, it was impossible
not to think back to that moment on the
porch, to hear a little voice in my
head say, with all the requisite
self-interest of a baby boomer: What"s
in it
for me? What will this mean in my
lifetime? Will I live longer, or better?
What"s in it for my parents, who have
both survived to about the predicted life
expectancy of people born now (79.5
years for women, 74.1 for men in this
country) but are not without medical
problems that will need addressing
sooner or later? And most of all, what
will it mean for my children, for all
children? When they reach middle age and
beyond, will they indeed avail
themselves of a vastly different
pharmacopoeia, a spectrum of treatments
that could well include cellular
therapies, replacement organs grown from
scratch, enzymes that immortalize cells?
Just how satisfying will that
longer life ultimately be, for myself
and my children? And what will it mean if
our society becomes disproportionately
weighted on the elderly end?
It is too soon to provide any
definitive answers to these questions,
but it"s a good time to begin asking
them. And, as I quickly began to learn,
there are plenty of strong and
conflicting opinions about this future,
beginning
with the man who, in a sense, started it
all.
Early the next morning, I followed the
final instructionsthe last of three
pagesto the Hayflick residence, a
handsome two-story contemporary
home on a little cul-de-sac overlooking
the ocean. The natural wildness of the
site was spectacular, but not nearly as
spectacular as the scientific story
Leonard Hayflick told inside. We spoke
for about seven hours (the fruits of
that conversation form the basis of
chapter 1), but one moment particularly
sticks in my mind.
It was late in the afternoon, after
many hours of talk, and Hayflick
was sitting on an ottoman in his living
room. The silvery light off the Pacific,
muted and dulled by high clouds on this
December day, nonetheless
seemed to ricochet off the white walls
and high ceilings of Hayflick"s home.
As soft and cool as the afternoon light
was, Leonard Hayflick was building up
an indignant head of steam. To those who
know him, including many who
admire his remarkable career in science,
the fact that he can still, at the
age of seventy-two, climb up on his high
horse is no surprise; he"s never
been one to hide his opinions, and for
much of his life he"s expressed those
opinions without reservation and lived
with the consequences. What
provoked his ire on this day was a
question I had asked. I admit to baiting
him a little, because I suspected what
his reaction might be, but I hadn"t
quite expected the magnitude of the
reply. I asked about a single word that
has increasingly crept into routine
scientific discourse, into newspaper
headlines, into New Age wish lists:
immortality.
Hayflick has been a prominent cell
biologist for four decades and
is a former president of the
Gerontological Society of America, so I
naturally
wanted to know what he thought about a
stream of recent public
statements by respectable scientists
regarding the prospects of significantly
extending the human life span through
the related technologies loosely
known as regenerative medicine, and the
increasing use of the I word. (I can"t
claim to have come to this discussion
with entirely clean hands; about a year
earlier I had written an article for the
New York Times Magazine about the
discovery and commercialization of
embryonic stem cells, and the
illustrationsnot my handiwork, I hasten
to adddepicted octogenarians
frolicking on scooters and in
convertibles, accompanied by the words
"Racing
Toward Immortality.")
Several days before I spoke with
Hayflick, for example, the first
annual meeting of the Society for
Regenerative Medicine convened in
Washington, D.C. In his remarks to the
group, William Haseltine, a cigar-smoking and ostentatiously optimistic bio-mogul who serves as chairman of the company Human Genome technologies stem cell therapy, tissue
engineering, and the use of gene-
related proteinswould change the way
medicine is practiced, and would
forever change our expectations of how
long we might live. More to the
point, Haseltine had been quoted several
times as predicting that twenty-first-
century medicine would achieve a kind of
"practical immortality."
Perhaps inevitably, the West Coast
version of this genre of
meeting took the form of the annual
gathering of the Extropy Institute in
Berkeley, a meeting attended by several
excellent hard-core molecular
biologists and later amusingly
chronicled by Brian Alexander in Wired
magazine. Michael Rose, an evolutionary
biologist at the University of
California at Irvine, was quoted as
saying, "I am now working on
immortality . . .Who gives a fuck what
people consider flaky! If it"s the truth,
it"s the truth." Cynthia Kenyon, a
well-respected molecular biologist at the
University of California at San
Francisco, spoke of her work identifying a
"grim-reaper gene" and a "fountain of
youth gene" in nematodes, and was
quoted as predicting that dramatic
life-span extension would become a reality
in the twenty-first century. Michael
West, the head of a company called
Advanced Cell Technology, did not attend
the meeting but was definitely
there in spirit. "We are close to
transferring the immortal
characteristics of
germ cells to our bodies and essentially
eliminating aging," he told
Wired. "That sounds spectacular, but I
believe those are the facts." In what
passed for scientific caution and
restraint, Calvin Harley, head scientist
at the
biotech company Geron, said he believed
it was not inevitable that
our "somas"our bodies are dead-end
carriers. "We are all born young,"
he said. "There is a capacity to have an
immortal propagation of cells. The
way we have evolved is to go from germ
line to germ line, with our somas the
dead-end carriers." "But,"he added,
"that is not inevitable."
As I recited each remark to Hayflick, I
could see him alternately
stiffen and squirm. "How shall I put
it?" he began after a long pause, clearly
offended by the hubris of his
colleagues, several of whom he considers
close friends. "I"ve been in this field
longer than any of the people that you"ve
mentioned, which," he conceded with a
laugh, "probably doesn"t mean a
helluva lot. But I"ll say it anyhow.
Every five years, for the past forty years,
there have been pronouncements made by
people with names other than
those that you mentioned, and with
expectations identical to the ones that
those people made. I"m still waiting.
And I"m afraid I"m going to wait not
only through my lifetime, but probably
forever.
"The problem," he continued, shifting
into second gear of his
dudgeon, "is that there is a failure to
understand the universality of a
phenomenon. If they can show me the
simplest way to prevent aging in
their own automobiles, to have them live
for a hundred years, then there will
be some reason to buy into the biology
argument. But they cannot do the
simple thing, like keep their cars from
aging for a twenty-year period, to say
nothing about biology. And furthermore,
what makes them think that the
molecules that compose living things are
any different from the molecules
that compose inanimate objects, in
respect to deterioration over time? And
finally, and probably the most telling
argument, which will never ever surface
in articles like that, is the stupid
question, Why do you want to do it in the
first place? What is the benefit? People
have this underlying, tacit belief
that increasing human longevity, or
curing aging, or however you want to
characterize it, is a good. They"ve
never asked themselves or never
described what that good is. And I
challenge all of them to provide a single
scenario that makes sense. Any scenario
that they"re liable to describe will
come closer to science fiction than
probable scientific reality."
"But," I replied, "it is in the air now."
"It"s been in the air since human
history has been written in
caves!" Hayflick almost shouted. "It"s
always been in the air. It"s no different
between now and any other period of
time. There just happen to be more
people involved. More people who haven"t
taken the time to understand this
field, unfortunately."
Hayflick had especially unkind words
for the genetics of aging, a
field that has recently exploded with
discoveries both in model organisms
like fruit flies and in human
centenarians. "There are no genes for
aging," he
insisted. "I"ll say that categorically,
and I"ll defend it despite what you have
heard and will hear from Cynthia Kenyon
and others. People like Kenyon
and Leonard Guarente and others are not
working in the field of aging at all.
They"re working in the field of, to be
liberal, longevity determination
Prologue 9 to be more specific,
developmental biology. Aging is a
deteriorative process, as most people
should know, and those folks are not
working with that aspect of the animals
they"re working with that involves
the deteriorative changes that occur
during aging. They"re manipulating
biological development with the
beautiful experiments that they"re
doing, and
there"s no denying that and I"m not
speaking to their experimental design. I"m
speaking to their understanding of what
aging is and what aging isn"t. The
fact is that everything will, whatever
the hell you do. Everything in the
universe ages."
Hayflick has earned the right to
express these opinions, because
he arguably laid the groundwork for the
entire field of molecular gerontology
the notion that aging, its causes as
well as potential remedies, might
fruitfully be attacked at the level of
cell biology and molecular intervention.
And he is well versed in the
demographics and statistics of longevity
determination; in fact, not long after
my visit he became so infuriated by the
reductionist hubris of some of his
fellow biologists that he teamed up with
gerontological demographer S. Jay
Olshansky and dozens of other prominent
aging experts to prepare a manifesto
decrying the misguided messages
imparted to the public about antiaging
research.
The would-be practitioners of
"practical immortality" were spinning
out a far more optimistic, revolutionary
view of the future. A couple of days
after visiting Hayflick, I paid a visit
to the laboratory of Cynthia Kenyon at
UCSF. Kenyon looks younger than her
forty-six years and, despite
locutions that sometimes flirt with
Valley Girl diction, possesses a breadth
and depth of knowledge that is
immediately apparent and instantly
intimidating. She cut her teeth working
under several of the most celebrated
molecular biologists of the last
half-century, including Sydney Brenner at
Cambridge and Mark Ptashne at Harvard,
and has narrowed her focus to
several intriguing genes in a small worm
known as Caenorhabditis elegans.
These tiny nematodes, when viewed
through a microscope, appear to have
no other purpose in life but to
endlessly carve sinuous arabesques in their
growth media, their movements
mesmerizing and beautiful. Whatever their
purpose in life, Kenyon and her
colleagues have found a way to extend that
lifequadruple it, in some casesby
altering a single gene. She is
unapologetically exuberant about the
possibilities this might hold for human
biology and human medicine.
"You know, if you look at an old worm
under a microscope, it has
all these tissues, and the tissues have
all our genes in themyou know,
myosin or transmitters, whateverand the
worm looks awful. And then you
change one gene and the whole worm, all
the tissues, looks good. So you"d
never think you could do that with one
gene. And once you see it happening
in a wormthe impossible has already
happened. What you would think
would be absolutely impossible is not
impossible. You can do that. Now,
whether you can do it in a human and
blah-blah-blah? Well, the big jump
has been taken. You can do it in an
animal. That"s the main thing. Whether
or not you can do it in a human? Maybe,
sure, I could see maybe you
couldn"t for some reason," she said,
pausing to give this possibility its
due. "But I doubt it." Although she
hedged her words scientifically during our
conversation, she has not hedged her
bets entrepreneurially. In the fall of
2000, she formed a company with MIT
scientist Leonard Guarente that has
as its ultimate goal the creation of
medicines that would extend the human
life span. One venture capitalist with
whom I spoke called it "the hottest
technology around right now."
In all the years she spent doing
elegant experiments on the
genetics of nematodes, Kenyon told me,
hardly anyone outside the
scientific community paid any attention
to what she had accomplished. But
as soon as she began to tackle the
molecular biology of aging, she was
inundated with requests for interviews.
"Night and day," she said, "night and
day. The public is absolutely fascinated
by aging. They don"t want to get old.
And you can seeread Shakespeare. Read
the sonnets. They"re all about
aging. A lot of people have an interest
in biology that really doesn"t extend
much further than their desire to cure a
disease, I think. But no one likes to
get old, and no one likes to see their
parents get old, or their
grandparents . . .You know, it"s just .
. ."and she reached for the right
sentiment"it"s a very, very powerful
human desire, I think, not to get old.
And you really feel that in a big way
when you study aging." That emotion
has become tethered to the
most sophisticated science of our time.
Longevity genes, replacement body
parts, stem cells,
immortalizing enzymesyou won"t find
reference to any of them in the
sonnets of Shakespeare. But Kenyon"s
remark inspired me to go back and
read the sonnets; I found that she was
right. There in abundance you will
find the timeless, anticipatory human
sadness about aging, about "winter"s
ragged hand" and "that churl death,"
that, four hundred years later, fires our
social fascination with the topic. We
prick our ears at any breakthrough,
whether marketed by clairvoyants or
molecular biologists, that purports to
arrest or Prologue 11 reverse the
inevitable process of aging, or even to
extend the human life span in such a way
that it no longer seems
preposterous to speak of a certain,
practical immortality.
But as Hayflick"s exasperation
suggests, there is an abiding
division and tension, even among
biologists, on whether the human life span
can be extended through better biology.
It is a debate that is going to be
played out before an extremely attentive
audience over the next decade or
so.
In my journey up to Sea Ranch, I later
realized, I had unintentionally
followed an earlier pilgrim, someone who
has perhaps understood the link
between the emotional, cultural longings
for an extended life span and the
science that might deliver it better
than anyone else in this story.
In the summer of 1992, a young man
named Michael West drove
those same roads, took those same
cliff-hugging turns past Monterey pine
and Douglas fir, passed that same wild
and ravishing seascape on the way
to visit Leonard Hayflick. For West,
this truly was a pilgrimage, a journey to
pay homage to a master, for Hayflick was
the scientist whose work had
prepared the bed in which all of West"s
dreams had begun to take root. A few
months earlier, in the fall of 1991,West
had blown away a roomful of jaded
West Coast venture capitalists with his
vision of creating a business to
develop medicines that would treat the
process of aging, based on several
cutting- edge molecular technologies
just then coming out of academic labs.
The money people had watered the seeds
of West"s ambitious ideas with
millions of dollars, and by March 1992,
he had a company on paper. It was
called Geron, and it was the first
biotechnology company explicitly devoted to
the molecular biology of aging.
West had much on his mind in those
dayshiring scientists,
finding lab space, riding herd on
research, scouting out new technologies.
But one of the first things he did was
drive up to see Hayflick. And Hayflick
was thrilled to have him. "He spent the
weekend up here," Hayflick
recalled, "and stayed in the guest room.
He was so riveted by this concept.
I took him out to dinner and he hardly
touched his food, he was so busy
talking about what he wanted to do. It
was very refreshing to see somebody
who I"ve known a few scientists who
burn with a white-hot flame, and
Mike is one of them."
They talked all weekend longboth are
excellent talkers and
storytellers. They talked about aging
research. They talked about
personalities in the field. They even
talked about some of the classic
medical textbooks in the field of aging,
and exchanged copies of first editions
of these seminal books. Hayflick showed
West the famous letter he had
received from a Nobel laureate,
rejecting for publication a 1961 paper that
subsequently became one of the most
widely cited in twentieth-century
science. "He was really one of the first
young people to enter the field who
had a sincere interest in the history of
aging research, and that was
extremely impressive," Hayflick told me.
"I thought to myself, "Here"s a fellow
to be cultivated."
"It"s immodest of me to say it,"
Hayflick continued, "but he knew
the history of the field, and he was
fascinated by my discovery of the limits
on cell replication in culture"the
discovery, that is, that cells grown in a
lab dish don"t, and can"t, live forever.
"And he just wanted to talk to me about
that. How did I discover it? What went
through my mind? What were my
views on the company, on its direction,
on people who might be hired? I
think that weekend stimulated him,
because he knew he could rely on me to
provide help, suggest people to contact,
and so on." Hayflick paused here,
then added, in a speculation rife with
implications, that he might also have
served as "kind of a father figure,
maybe" for West.
That speculation may actually get
closer to the reality of things,
not least because it hints at the way in
which that relationship may have
influenced a pitched public-policy
debate nearly a decade later. While there
is no question about the crucial role
Leonard Hayflick played in the early
days of molecular biology"s attack on
aging, and how his early experiments
have inspired a fabulously productive
area of contemporary science, what"s
far less appreciated is how he also
served as a role model and inspiration
for Michael Westnot simply for his
science, although that was important,
but for his attitude, his temperamental
readiness to defy authority, and his
willingness to pay a price, an enormous
and almost unconscionable price,
to do something he believed was right,
even when everyone else in the world
believed he was wrong. And it"s quite
possible that after his weekend at
Sea Ranch, West appreciatedas does
almost anyone who speaks at
length with Hayflicka deeper moral to
Hayflick"s story. Although he can be
stubborn and antagonistic and even
bombastic, perhaps Leonard Hayflick"s
greatest sin and scientific
transgression was that he was way ahead
of his
time. It was a lesson that West, who
shares many of the same qualities,
took to heart.
Copyright 2003 by Stephen S. Hall.
Reprinted by permission of Houghton
Mifflin Company.
Reviews:
smoking and ostentatiously optimistic
bio-mogul who serves as chairman of
the company Human Genome Sciences,
predicted that several emerging
technologies stem cell therapy, tissue
engineering, and the use of gene-
related proteinswould change the way
medicine is practiced, and would
forever change our expectations of how
long we might live. More to the
point, Haseltine had been quoted several
times as predicting that twenty-first-
century medicine would achieve a kind of
"practical immortality."
Perhaps inevitably, the West Coast
version of this genre of
meeting took the form of the annual
gathering of the Extropy Institute in
Berkeley, a meeting attended by several
excellent hard-core molecular
biologists and later amusingly
chronicled by Brian Alexander in Wired
magazine. Michael Rose, an evolutionary
biologist at the University of
California at Irvine, was quoted as
saying, "I am now working on
immortality . . .Who gives a fuck what
people consider flaky! If it"s the truth,
it"s the truth." Cynthia Kenyon, a
well-respected molecular biologist at the
University of California at San
Francisco, spoke of her work identifying a
"grim-reaper gene" and a "fountain of
youth gene" in nematodes, and was
quoted as predicting that dramatic
life-span extension would become a reality
in the twenty-first century. Michael
West, the head of a company called
Advanced Cell Technology, did not attend
the meeting but was definitely
there in spirit. "We are close to
transferring the immortal
characteristics of
germ cells to our bodies and essentially
eliminating aging," he told
Wired. "That sounds spectacular, but I
believe those are the facts." In what
passed for scientific caution and
restraint, Calvin Harley, head scientist
at the
biotech company Geron, said he believed
it was not inevitable that
our "somas"our bodies are dead-end
carriers. "We are all born young,"
he said. "There is a capacity to have an
immortal propagation of cells. The
way we have evolved is to go from germ
line to germ line, with our somas the
dead-end carriers." "But,"he added,
"that is not inevitable."
As I recited each remark to Hayflick, I
could see him alternately
stiffen and squirm. "How shall I put
it?" he began after a long pause, clearly
offended by the hubris of his
colleagues, several of whom he considers
close friends. "I"ve been in this field
longer than any of the people that you"ve
mentioned, which," he conceded with a
laugh, "probably doesn"t mean a
helluva lot. But I"ll say it anyhow.
Every five years, for the past forty years,
there have been pronouncements made by
people with names other than
those that you mentioned, and with
expectations identical to the ones that
those people made. I"m still waiting.
And I"m afraid I"m going to wait not
only through my lifetime, but probably
forever.
"The problem," he continued, shifting
into second gear of his
dudgeon, "is that there is a failure to
understand the universality of a
phenomenon. If they can show me the
simplest way to prevent aging in
their own automobiles, to have them live
for a hundred years, then there will
be some reason to buy into the biology
argument. But they cannot do the
simple thing, like keep their cars from
aging for a twenty-year period, to say
nothing about biology. And furthermore,
what makes them think that the
molecules that compose living things are
any different from the molecules
that compose inanimate objects, in
respect to deterioration over time? And
finally, and probably the most telling
argument, which will never ever surface
in articles like that, is the stupid
question, Why do you want to do it in the
first place? What is the benefit? People
have this underlying, tacit belief
that increasing human longevity, or
curing aging, or however you want to
characterize it, is a good. They"ve
never asked themselves or never
described what that good is. And I
challenge all of them to provide a single
scenario that makes sense. Any scenario
that they"re liable to describe will
come closer to science fiction than
probable scientific reality."
"But," I replied, "it is in the air now."
"It"s been in the air since human
history has been written in
caves!" Hayflick almost shouted. "It"s
always been in the air. It"s no different
between now and any other period of
time. There just happen to be more
people involved. More people who haven"t
taken the time to understand this
field, unfortunately."
Hayflick had especially unkind words
for the genetics of aging, a
field that has recently exploded with
discoveries both in model organisms
like fruit flies and in human
centenarians. "There are no genes for
aging," he
insisted. "I"ll say that categorically,
and I"ll defend it despite what you have
heard and will hear from Cynthia Kenyon
and others. People like Kenyon
and Leonard Guarente and others are not
working in the field of aging at all.
They"re working in the field of, to be
liberal, longevity determination
Prologue 9 to be more specific,
developmental biology. Aging is a
deteriorative process, as most people
should know, and those folks are not
working with that aspect of the animals
they"re working with that involves
the deteriorative changes that occur
during aging. They"re manipulating
biological development with the
beautiful experiments that they"re
doing, and
there"s no denying that and I"m not
speaking to their experimental design. I"m
speaking to their understanding of what
aging is and what aging isn"t. The
fact is that everything will, whatever
the hell you do. Everything in the
universe ages."
Hayflick has earned the right to
express these opinions, because
he arguably laid the groundwork for the
entire field of molecular gerontology
the notion that aging, its causes as
well as potential remedies, might
fruitfully be attacked at the level of
cell biology and molecular intervention.
And he is well versed in the
demographics and statistics of longevity
determination; in fact, not long after
my visit he became so infuriated by the
reductionist hubris of some of his
fellow biologists that he teamed up with
gerontological demographer S. Jay
Olshansky and dozens of other prominent
aging experts to prepare a manifesto
decrying the misguided messages
imparted to the public about antiaging
research.
The would-be practitioners of
"practical immortality" were spinning
out a far more optimistic, revolutionary
view of the future. A couple of days
after visiting Hayflick, I paid a visit
to the laboratory of Cynthia Kenyon at
UCSF. Kenyon looks younger than her
forty-six years and, despite
locutions that sometimes flirt with
Valley Girl diction, possesses a breadth
and depth of knowledge that is
immediately apparent and instantly
intimidating. She cut her teeth working
under several of the most celebrated
molecular biologists of the last
half-century, including Sydney Brenner at
Cambridge and Mark Ptashne at Harvard,
and has narrowed her focus to
several intriguing genes in a small worm
known as Caenorhabditis elegans.
These tiny nematodes, when viewed
through a microscope, appear to have
no other purpose in life but to
endlessly carve sinuous arabesques in their
growth media, their movements
mesmerizing and beautiful. Whatever their
purpose in life, Kenyon and her
colleagues have found a way to extend that
lifequadruple it, in some casesby
altering a single gene. She is
unapologetically exuberant about the
possibilities this might hold for human
biology and human medicine.
"You know, if you look at an old worm
under a microscope, it has
all these tissues, and the tissues have
all our genes in themyou know,
myosin or transmitters, whateverand the
worm looks awful. And then you
change one gene and the whole worm, all
the tissues, looks good. So you"d
never think you could do that with one
gene. And once you see it happening
in a wormthe impossible has already
happened. What you would think
would be absolutely impossible is not
impossible. You can do that. Now,
whether you can do it in a human and
blah-blah-blah? Well, the big jump
has been taken. You can do it in an
animal. That"s the main thing. Whether
or not you can do it in a human? Maybe,
sure, I could see maybe you
couldn"t for some reason," she said,
pausing to give this possibility its
due. "But I doubt it." Although she
hedged her words scientifically during our
conversation, she has not hedged her
bets entrepreneurially. In the fall of
2000, she formed a company with MIT
scientist Leonard Guarente that has
as its ultimate goal the creation of
medicines that would extend the human
life span. One venture capitalist with
whom I spoke called it "the hottest
technology around right now."
In all the years she spent doing
elegant experiments on the
genetics of nematodes, Kenyon told me,
hardly anyone outside the
scientific community paid any attention
to what she had accomplished. But
as soon as she began to tackle the
molecular biology of aging, she was
inundated with requests for interviews.
"Night and day," she said, "night and
day. The public is absolutely fascinated by aging. They don"t want to get old. And you can seeread Shakespeare. Read
the sonnets. They"re all about
aging. A lot of people have an interest
in biology that really doesn"t extend
much further than their desire to cure a
disease, I think. But no one likes to
get old, and no one likes to see their
parents get old, or their
grandparents . . .You know, it"s just .
. ."and she reached for the right
sentiment"it"s a very, very powerful
human desire, I think, not to get old.
And you really feel that in a big way
when you study aging." That emotion
has become tethered to the
most sophisticated science of our time.
Longevity genes, replacement body
parts, stem cells,
immortalizing enzymesyou won"t find
reference to any of them in the
sonnets of Shakespeare. But Kenyon"s
remark inspired me to go back and
read the sonnets; I found that she was
right. There in abundance you will
find the timeless, anticipatory human
sadness about aging, about "winter"s
ragged hand" and "that churl death,"
that, four hundred years later, fires our
social fascination with the topic. We
prick our ears at any breakthrough,
whether marketed by clairvoyants or
molecular biologists, that purports to
arrest or Prologue 11 reverse the
inevitable process of aging, or even to
extend the human life span in such a way
that it no longer seems
preposterous to speak of a certain,
practical immortality.
But as Hayflick"s exasperation
suggests, there is an abiding
division and tension, even among
biologists, on whether the human life span
can be extended through better biology.
It is a debate that is going to be
played out before an extremely attentive
audience over the next decade or
so.
In my journey up to Sea Ranch, I later
realized, I had unintentionally
followed an earlier pilgrim, someone who
has perhaps understood the link
between the emotional, cultural longings
for an extended life span and the
science that might deliver it better
than anyone else in this story.
In the summer of 1992, a young man
named Michael West drove
those same roads, took those same
cliff-hugging turns past Monterey pine
and Douglas fir, passed that same wild
and ravishing seascape on the way
to visit Leonard Hayflick. For West,
this truly was a pilgrimage, a journey to
pay homage to a master, for Hayflick was
the scientist whose work had
prepared the bed in which all of West"s
dreams had begun to take root. A few
months earlier, in the fall of 1991,West
had blown away a roomful of jaded
West Coast venture capitalists with his
vision of creating a business to
develop medicines that would treat the
process of aging, based on several
cutting- edge molecular technologies
just then coming out of academic labs.
The money people had watered the seeds
of West"s ambitious ideas with
millions of dollars, and by March 1992,
he had a company on paper. It was
called Geron, and it was the first
biotechnology company explicitly devoted to
the molecular biology of aging.
West had much on his mind in those
dayshiring scientists,
finding lab space, riding herd on
research, scouting out new technologies.
But one of the first things he did was
drive up to see Hayflick. And Hayflick
was thrilled to have him. "He spent the
weekend up here," Hayflick
recalled, "and stayed in the guest room.
He was so riveted by this concept.
I took him out to dinner and he hardly
touched his food, he was so busy
talking about what he wanted to do. It
was very refreshing to see somebody
who I"ve known a few scientists who
burn with a white-hot flame, and
Mike is one of them."
They talked all weekend longboth are
excellent talkers and
storytellers. They talked about aging
research. They talked about
personalities in the field. They even
talked about some of the classic
medical textbooks in the field of aging,
and exchanged copies of first editions
of these seminal books. Hayflick showed
West the famous letter he had
received from a Nobel laureate,
rejecting for publication a 1961 paper that
subsequently became one of the most
widely cited in twentieth-century
science. "He was really one of the first
young people to enter the field who
had a sincere interest in the history of
aging research, and that was
extremely impressive," Hayflick told me.
"I thought to myself, "Here"s a fellow
to be cultivated."
"It"s immodest of me to say it,"
Hayflick continued, "but he knew
the history of the field, and he was
fascinated by my discovery of the limits
on cell replication in culture"the
discovery, that is, that cells grown in a
lab dish don"t, and can"t, live forever.
"And he just wanted to talk to me about
that. How did I discover it? What went
through my mind? What were my
views on the company, on its direction,
on people who might be hired? I
think that weekend stimulated him,
because he knew he could rely on me to
provide help, suggest people to contact,
and so on." Hayflick paused here,
then added, in a speculation rife with
implications, that he might also have
served as "kind of a father figure,
maybe" for West.
That speculation may actually get
closer to the reality of things,
not least because it hints at the way in
which that relationship may have
influenced a pitched public-policy
debate nearly a decade later. While there
is no question about the crucial role
Leonard Hayflick played in the early
days of molecular biology"s attack on
aging, and how his early experiments
have inspired a fabulously productive
area of contemporary science, what"s
far less appreciated is how he also
served as a role model and inspiration
for Michael Westnot simply for his
science, although that was important,
but for his attitude, his temperamental
readiness to defy authority, and his
willingness to pay a price, an enormous
and almost unconscionable price,
to do something he believed was right,
even when everyone else in the world
believed he was wrong. And it"s quite
possible that after his weekend at
Sea Ranch, West appreciatedas does
almost anyone who speaks at
length with Hayflicka deeper moral to
Hayflick"s story. Although he can be
stubborn and antagonistic and even
bombastic, perhaps Leonard Hayflick"s
greatest sin and scientific
transgression was that he was way ahead
of his
time. It was a lesson that West, who
shares many of the same qualities,
took to heart.
Copyright 2003 by Stephen S. Hall.
Reprinted by permission of Houghton
Mifflin Company.
Revolution in Progress
So, when will stem cells come into widespread medical use? If you answer twenty years from now, you'd be wrong by about 60 years--they first became widely used in the 1960's! Only they were called "bone marrow transplants." Today thousands of them are done every year.
Hall has written a dozen so excellent books on medicine, biotechnology and molecular biology, and this is one of the best. Here he recounts the development of the idea that aging in humans can be scientifically understood and modified. He starts off with the wonderful story of the Hayflick limit with an account of his first interview with him and brings this maverick character to life. How often are the big ideas discovered by rogues and rebels--fearless men?
He covers a very wide swath of current developments in the cutting edge of biology and medicine--telomeres, stem cells, transplants, cloning, and aging--all told in enough depth that you can't help but learn something, even if you are pretty well informed. The history, the personalities, and the ideas are all here.
One thing I appreciated is that Hall makes no pretense about being disinterested in the subject--he takes some of it personally, and is not afraid to relate what his gut is telling him. He is partisan in the best sense of the word. He unflinchingly challenges the idealistic "bioethicists" who have lately ejected such nonsense into the public space, pretending to a certainty only a bishop could appreciate.
Hall also relates in some detail the evolution of the stem cell/cloning debate that has resulted in the policy that federal money can go to research only on the 70 embryonic stem cell lines already in existence, now known to be more like 6. And none of them suitable for therapeutic for humans because they are grown on a substrate of mouse cells and their viruses. The yokels and theologians have managed to set back this important avenue for improving human health by who knows how many decades... Sad to think we'll be looking for progress to the South Koreans, who recently generated human embryonic cell lines by nuclear transfer. Americans have yet to duplicate this
The quality of Hall's prose, and the nature of the subject itself, conspire to produce a book that I found very hard to put down. A terrific read!
Meet the masters of biohope and biohype
Stephen Hall has chosen a title that represents his book very well. What he sets forth, in supple, thoughtful, smoothly readable prose, is the saga of recent advances in "life extension" - both longevity research and research into the healing and regeneration of tissues with the aid of stem cells. As his title suggests, the emphasis is on the scientists involved, and on the public face of that science.
Along the way, he clarifies a good deal of the science itself: the discovery of the Hayflick limit, the finite limit to the number of times a normal cell can divide; the connection of that limit to the telomeres, the shoelace-tips on the ends of chromosomes; the chimerical enzyme telomerase, two parts protein and one part RNA, which repairs the telomeres and helps make cancer cells immortal; the sir-1 gene and its congeners which can double or sextuple your lifespan, if you happen to be a roundworm. And so on. Little of this will be news to those laymen who follow the science pages closely, but even for us it's good to have the timeline neatly laid out.
The bulk of Hall's attention, though, goes to the rivalries between laboratories to be first to publish and patent each of these breakthroughs; to the lineages of the biotech startups bankrolling the races; to the contrast between the solid if limited gains made by the biologists and the fairy dust sprinkled on investors; and to the enormous ferment surrounding all these new technologies as they began to impinge on embryonic stem cells and thereapeutic cloning.
Wandering through the scene from chapter to chapter, popping up repeatedly whenever the action gets hot, is the energetic true believer Michael West, the ousted founder of the premiere telomere outfit Geron, and the leading light of Advanced Cell Technology, which set the country on its ear two years ago with a premature announcement that it had cloned a human embryo. In his infectious zeal for abolishing the tyranny of old age, West serves not only as a central figure in the unfolding commercial and political saga, but as a stand-in for the insistent voice in all of us, whispering that all men may be mortal, but hey, maybe *you* can beat the rap.
Hall's conclusion, offered with a full appreciation of the fact that "It's hard to predict things, especially the future," is that a dramatic cure for aging is not likely to be in the cards. Just as cancer turned out to be a whole class of diseases with a host of different causes, so aging is turning out to be more complex than the discipline's pioneers imagined. What we can reasonably expect is a steady advancement of the average life span over the coming century, by another decade or two. How long we have to wait for breakthroughs in tissue regeneration in particular will likely depend less on science than on politics.
Two intriguing lines of lifespan research, the one tracking the sir family of genes, and the one investigating the effects of free radicals, are not ignored but, perhaps because they haven't caught the public fancy sharply, get relatively short shrift. Less than halfway through the book, the spotlight shifts from the study of aging to the study of stem cells. Because the U.S. for the last quarter century has enjoyed an effective moratorium on experimentation with aborted fetuses or discarded IVC embryos, American scientists' attention has focused more and more on the other theoretical way of obtaining human embryos: inserting the nucleus of an adult cell into an enucleated human egg.
If anyone were to succeed in doing that, and coaxing the result to divide until it reached the blastocyst stage - that would be "therapeutic cloning." So far, no one's done it, or at any rate no one who's done it has felt like advertising it. In a political squaring of the circle, President Bush managed to permit NIH to fund limited therapeutic cloning in a way that ended up outlawing funding in practical terms. As a result, scientists in the field face the classic NRA nightmare: when federal stem cells are outlawed, only maverick venture capitalists will have stem cells. At press time, no one knows what's really happening, what kind of ethical oversight private companies are bothering to put in place, or how restricted access to resulting medical breakthroughs will be when it's all proprietary, with no NIH ownership at all. For the moment, the U.S. is stuck with the worst of the "pro-life" and the "mad scientist" worlds, while the rest of the world does its research in the sunlight and steals a technical march on us.
All the players on both sides of that circle-squaring, and the principal shakers, movers and move-blockers in the relevant research, are profiled here, some in full screen 3-d and some in fetching thumbnails. The field is unlikely to be surveyed by a more complete or more even handed chronicler for some while.