[Paleopsych] NYTBR: 'Radical Evolution' and 'More Than Human': The Incredibles

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'Radical Evolution' and 'More Than Human': The Incredibles
New York Times Book Review, 5.7.3
[First chapter of More than Human appended.]

The Promise and Peril of Enhancing Our Minds, Our Bodies -- and What It Means 
to Be Human.
By Joel Garreau.
384 pp. Doubleday. $26.

Embracing the Promise of Biological Enhancement.
By Ramez Naam.
276 pp. Broadway Books. $24.95.


    ''This book can't begin with the tale of the telekinetic monkey.'' So
    opens Joel Garreau's captivating, occasionally brilliant and often
    exasperating ''Radical Evolution.'' Garreau, a reporter and editor at
    The Washington Post and the author of the influential work of social
    demography ''Edge City,'' acknowledges his authorial choice is a
    sacrifice. After all, ''how often does someone writing nonfiction get
    to lead with a monkey who can move objects with her thoughts?'' But to
    begin his book about the technological enhancement of the human mind
    and body with this kind of gee-whiz gimmick would send a misleading
    signal. Garreau makes it clear he's more interested in people than in

    Readers will be grateful, since an airless sterility often creeps into
    books like ''Radical Evolution,'' which is focused on the near future.
    In the next generation or two, Garreau writes, advances in genetics,
    robotics, information technology and nanotechnology (the science that
    permits the construction of infinitesimally tiny devices) may allow us
    to raise our intelligence, refine our bodies and even become immortal
    -- or they could lead to a ruinous disruption of our individual
    identities and shared institutions, and if things go really wrong, to
    the total destruction of humanity.

    Unless you've cultivated a taste for the hypothetical, the situations
    mapped out here, in which computers take over, can become so much
    numbing science fiction. Wisely, Garreau devotes himself to embedding
    these unfamiliar technologies in a human context. We meet researchers
    from the federal government's mysterious Defense Advanced Research
    Projects Agency, now engineering soldiers who don't need sleep and who
    can stop a wound from bleeding just by thinking about it. We spend
    time with scientists at a biotechnology firm called Functional
    Genetics, engaged in research on ''anti-infectives'' that could one
    day make humans invulnerable to AIDS, Alzheimer's and cancer.

    Garreau focuses on three camps of thinkers who have paused to
    contemplate the future. The first espouse what Garreau terms the
    ''Heaven Scenario.'' They believe enhancement technology will allow us
    to live forever in perfect happiness without pain, more or less. The
    most vigorous advocate of what one skeptic calls ''techno-exuberance''
    is Ray Kurzweil, an inventor and futurist. ''I'm not planning to
    die,'' Kurzweil announces. Instead, he speculates that humans will one
    day upload the contents of their brains to a computer and shed their
    physical bodies altogether.

    Set opposite Kurzweil and his buoyancy is Bill Joy, a founder of Sun
    Microsystems, whose musings tend toward the apocalyptic. Well known
    for his dire warnings about the growing power of technology, the
    misnamed Joy represents what Garreau calls the ''Hell Scenario.'' Joy
    speculates that we may meet an undignified end in ''gray goo,'' a
    scenario in which self-replicating devices designed to improve our
    bodies and minds instead take on a life of their own, becoming ''too
    tough, too small and too rapidly spreading to stop.'' They may, Joy
    continues, eventually ''suck everything vital out of all living
    things, reducing their husks to ashy mud in a matter of days.''

    Things really get interesting when Garreau meets up with Jaron Lanier,
    a computer scientist and originator of the concept of virtual reality.
    Lanier foresees neither nirvana nor apocalypse, but a future in which
    every technological crisis is met and matched by our own ingenuity and
    resilience. Garreau christens this the ''Prevail Scenario,'' and
    confesses his personal preference for this vision animated by what he
    calls his ''faith in human cussedness.'' Heaven and hell share the
    same story line, he writes: ''We are in for revolutionary change;
    there's not much we can do about it; hang on tight; the end. The
    Prevail Scenario, if nothing else, has better literary qualities.''

    Garreau's style often takes the form of a notebook dump, in which he
    deposits his assorted jottings directly onto the page. Sometimes the
    results are stultifying, but when the subject has a mind as original
    as Lanier's, they're enthralling. Lanier's reflections are at once
    whimsical and serious: What if we could project our thoughts and
    feelings so that they were instantly visible to others? What if our
    superintelligent machines are felled by a Windows crash, just as
    they're about to take over?

    To read Garreau's dazzling, disorderly book is to be thrust into a
    bewildering new world, where ambiguity rules and familiar signposts
    are few. As he observes, ''by the time the future has all its wires
    carefully tucked away in a nice metal box where you can no longer see
    the gaffer tape, it is no longer the future.''

    Whereas Garreau's portraits make it clear that ideas about the future
    are always idiosyncratic and subjective, rooted as much in emotional
    need as in rational analysis, there's no such nuance in Ramez Naam's
    ''More Than Human.'' Naam, a professional technologist who helped
    develop Microsoft Outlook and Microsoft Internet Explorer, is a
    relentlessly positive pitchman, unburdened by doubt or complexity. But
    his conception of our enhanced future looks less like Kurzweil's sunny
    utopia and more like a fluorescent-lighted superstore, in which we
    roam the aisles selecting from displays of brain implants and
    anti-aging pills.

    To Naam, the technological augmentation of our minds and bodies is not
    an ethical or philosophical question but just one more consumer
    choice. Accordingly, his main concern is with governmental
    interference in the free market for such devices. People should be
    allowed to make up their own minds about enhancements, Naam argues,
    since ''millions of individuals weighing costs and benefits have a
    greater collective intelligence, better collective judgment, than a
    small number of centralized regulators and controllers.'' Never mind
    that we don't allow citizens' ''collective judgment'' to decide which
    drugs are safe; that's why we have the F.D.A. Expert guidance, based
    on long-term, large-scale research, would seem even more essential in
    the case of activities like germline genetic engineering, which
    permanently changes the genetic code of an individual and all his or
    her descendants.

    Naam's other targets are those who seek to slow or even arrest
    research on biotechnology. Though these objectors span the ideological
    spectrum -- from Bill McKibben, the liberal author of ''Enough,'' to
    Leon R. Kass, the conservative chairman of the President's Council on
    Bioethics -- Naam lumps them all together as curmudgeonly sticks in
    the mud, ''advocates of the biological status quo.'' Yet just one page
    earlier Naam talks up the wonders of ''keeping people young longer''
    through science. He seems not to notice that eternal youth -- along
    with faultless functioning, perpetual fertility and unfailingly
    pleasant mood -- is its own kind of frozen status quo.

    In fact, there's something peculiarly adolescent about the blend of
    narcissism, self-indulgence and lust for control that appears to
    motivate this quest to become ''more than human.'' Naam's book fails
    to grapple adequately with the consequences that may follow if,
    through technology, some of these limits are lifted. In hailing a drug
    that makes long-married couples feel like newlyweds again, or a neural
    prosthesis that allows you to ''turn down the volume'' on your brain's
    ''empathy centers,'' or gene therapy that bulks up your muscles
    ''while you're watching television,'' Naam and his fellow enhancement
    boosters seem unwilling to reckon with the fact that the same limits
    that make life difficult also give it meaning.

    Annie Murphy Paul is the author of ''The Cult of Personality: How
    Personality Tests Are Leading Us to Miseducate Our Children, Mismanage
    Our Companies, and Misunderstand Ourselves.''


First chapter of 'More Than Human'


    In 1989, Raj and Van DeSilva were desperate. Their daughter Ashanti,
    just four, was dying. She was born with a crippled immune system, a
    consequence of a problem in her genes.

    Every human being has around thirty thousand genes. In fact, we have
    two copies of each of those genes-one inherited from our mother, the
    other from our father. Our genes tell our cells what proteins to make,
    and when. Each protein is a tiny molecular machine. Every cell in your
    body is built out of millions of these little machines, working
    together in precise ways. Proteins break down food, ferry energy to
    the right places, and form scaffoldings that maintain cell health and
    structure. Some proteins synthesize messenger molecules to pass
    signals in the brain, and other proteins form receptors to receive
    those signals. Even the machines inside each of your cells that build
    new proteins-called ribosomes-are themselves made up of other

    Ashanti DeSilva inherited two broken copies of the gene that contains
    the instructions for manufacturing a protein called adenoside
    deaminase (ADA). If she had had just one broken copy, she would have
    been fine. The other copy of the gene would have made up the
    difference. With two broken copies, her body didn't have the right
    instructions to manufacture ADA at all.

    ADA plays a crucial role in our resistance to disease. Without it,
    special white blood cells called T cells die off. Without T cells,
    ADA-deficient children are wide open to the attacks of viruses and
    bacteria. These children have what's called severe combined immune
    deficiency (SCID) disorder, more commonly known as bubble boy disease.

    To a person with a weak immune system, the outside world is
    threatening. Everyone you touch, share a glass with, or share the same
    air with is a potential source of dangerous pathogens. Lacking the
    ability to defend herself, Ashanti was largely confined to her home.

    The standard treatment for ADA deficiency is frequent injections of
    PEG-ADA, a synthetic form of the ADA enzyme. PEG-ADA can mean the
    difference between life and death for an ADA-deficient child.
    Unfortunately, although it usually produces a rapid improvement when
    first used, children tend to respond less and less to the drug each
    time they receive a dose. Ashanti DeSilva started receiving PEG-ADA
    injections at the age of two, and initially she responded well. Her
    T-cell count rose sharply and she developed some resistance to
    disease. But by the age of four, she was slipping away, no longer
    responding strongly to her injections. If she was to live, she'd need
    something more than PEG-ADA. The only other option at the time, a
    bone-marrow transplant, was ruled out by the lack of matching donors.

    In early 1990, while Ashanti's parents were searching frantically for
    help, French Anderson, a geneticist at the National Institutes of
    Health, was seeking permission to perform the first gene-therapy
    trials on humans. Anderson, an intense fifth-degree blackbelt in tae
    kwon do and respected researcher in the field of genetics, wanted to
    show that he could treat genetic diseases caused by faulty copies of
    genes by inserting new, working copies of the same gene.

    Scientists had already shown that it was possible to insert new genes
    into plants and animals. Genetic engineering got its start in 1972,
    when geneticists Stanley Cohen and Herbert Boyer first met at a
    scientific conference in Hawaii on plasmids, small circular loops of
    extra chromosomal DNA in which bacteria carry their genes. Cohen, then
    a professor at Stanford, had been working on ways to insert new
    plasmids into bacteria. Researchers in Boyer's lab at the University
    of California in San Francisco had recently discovered restriction
    enzymes, molecular tools that could be used to slice and dice DNA at
    specific points.

    Over hot pastrami and corned-beef sandwiches, the two Californian
    researchers concluded that their technologies complemented one
    another. Boyer's restriction enzymes could isolate specific genes, and
    Cohen's techniques could then deliver them to bacteria. Using both
    techniques researchers could alter the genes of bacteria. In 1973,
    just four months after meeting each other, Cohen and Boyer inserted a
    new gene into the Escherichia coli bacterium (a regular resident of
    the human intestine).

    For the first time, humans were tinkering directly with the genes of
    another species. The field of genetic engineering was born. Boyer
    would go on to found Genentech, the world's first biotechnology
    company. Cohen would go on to win the Nobel Prize in 1986 for his work
    on cell growth factors.

    Building on Cohen and Boyer's work with bacteria, hundreds of
    scientists went on to find ways to insert new genes into plants and
    animals. The hard work of genetically engineering these higher
    organisms lies in getting the new gene into the cells. To do this, one
    needs a gene vector-a way to get the gene to the right place. Most
    researchers use gene vectors provided by nature: viruses. In some
    ways, viruses are an ideal tool for ferrying genes into a cell,
    because penetrating cell walls is already one of their main abilities.
    Viruses are cellular parasites. Unlike plant or animal cells, or even
    bacteria, viruses can't reproduce themselves. Instead, they penetrate
    cells and implant their viral genes; these genes then instruct the
    cell to make more of the virus, one protein at a time.

    Early genetic engineers realized that they could use viruses to
    deliver whatever genes they wanted. Instead of delivering the genes to
    create more virus, a virus could be modified to deliver a different
    gene chosen by a scientist. Modified viruses were pressed into service
    as genetic "trucks," carrying a payload of genes loaded onto them by
    researchers; these viruses don't spread from cell to cell, because
    they don't carry the genes necessary for the cell to make new copies
    of the virus.

    By the late 1980s, researchers had used this technique to alter the
    genes of dozens of species of plants and animals-tobacco plants that
    glow, tomatoes that could survive freezing, corn resistant to
    pesticides. French Anderson and his colleagues reasoned that one could
    do the same in a human being. Given a patient who lacked a gene
    crucial to health, one ought to be able to give that person copies of
    the missing gene. This is what Anderson proposed to do for Ashanti.

    Starting in June of 1988, Anderson's proposed clinical protocols, or
    treatment plans, went through intense scrutiny and generated more than
    a little hostility. His first protocol was reviewed by both the
    National Institutes of Health (NIH) and the Food and Drug
    Administration (FDA). Over a period of seven months, seven regulatory
    committees conducted fifteen meetings and twenty hours of public
    hearings to assess the proposal.

    In early 1990, Anderson and his collaborators received the final
    approval from the NIH's Recombinant DNA Advisory Committee and had
    cleared all legal hurdles. By spring, they had identified Ashanti as a
    potential patient. Would her parents consent to an experimental
    treatment? Of course there were risks to the therapy, yet without it
    Ashanti would face a life of seclusion and probably death in the next
    few years. Given these odds, her parents opted to try the therapy. As
    Raj DeSilva told the Houston Chronicle, "What choice did we have?"

    Ashanti and her parents flew to the NIH Clinical Center at Bethesda,
    Maryland. There, over the course of twelve days, Anderson and his
    colleagues Michael Blaese and Kenneth Culver slowly extracted some of
    Ashanti's blood cells. Safely outside the body, the cells had new,
    working copies of the ADA gene inserted into them by a hollowed-out
    virus. Finally, starting on the afternoon of September 14, Culver
    injected the cells back into Ashanti's body.

    The gene therapy had roughly the same goal as a bone-marrow
    transplant-to give Ashanti a supply of her own cells that could
    produce ADA. Unlike a bone-marrow transplant, gene therapy carries no
    risk of rejection. The cells Culver injected back into Ashanti's
    bloodstream were her own, so her body recognized them as such.

    The impact of the gene therapy on Ashanti was striking. Within six
    months, her T-cell count rose to normal levels. Over the next two
    years, her health continued to improve, allowing her to enroll in
    school, venture out of the house, and lead a fairly normal childhood.

    Ashanti is not completely cured-she still takes a low dose of PEG-ADA.
    Normally the dose size would increase with the patient's age, but her
    doses have remained fixed at her four-year-old level. It's possible
    that she could be taken off the PEG-ADA therapy entirely, but her
    doctors don't think it's yet worth the risk. The fact that she's alive
    today-let alone healthy and active-is due to her gene therapy, and
    also helps prove a crucial point: genes can be inserted into humans to
    cure genetic diseases.

    From Healing to Enhancing

    After Ashanti's treatment, the field of gene therapy blossomed. Since
    1990, hundreds of labs have begun experimenting with gene therapy as a
    technique to cure disease, and more than five hundred human trials
    involving over four thousand patients have been launched. Researchers
    have shown that it may be possible to use gene therapy to cure
    diabetes, sickle-cell anemia, several kinds of cancer, Huntington's
    disease and even to open blocked arteries.

    While the goal of gene therapy researchers is to cure disease, gene
    therapy could also be used to boost human athletic performance. In
    many cases, the same research that is focused on saving lives has also
    shown that it can enhance the abilities of animals, with the
    suggestion that it could enhance men and women as well.

    Consider the use of gene therapy to combat anemia. Circulating through
    your veins are trillions of red blood cells. Pumped by your heart,
    they serve to deliver oxygen from the lungs to the rest of your
    tissues, and carry carbon dioxide from the tissues back out to the
    lungs and out of the body. Without enough red blood cells, you can't
    function. Your muscles can't get enough oxygen to produce force, and
    your brain can't get enough oxygen to think clearly. Anemia is the
    name of the condition of insufficient red blood cells. Hundreds of
    thousands of people worldwide live with anemia, and with the lethargy
    and weakness that are its symptoms. In the United States, at least
    eighty-five thousand patients are severely anemic as a result of
    kidney failure. Another fifty thousand AIDS patients are anemic due to
    side effects of the HIV drug AZT.

    In 1985, researchers at Amgen, a biotech company based in Thousand
    Oaks, California, looking for a way to treat anemia isolated the gene
    responsible for producing the growth hormone erythropoietin (EPO).
    Your kidneys produce EPO in response to low levels of oxygen in the
    blood. EPO in turn causes your body to produce more red blood cells.
    For a patient whose kidneys have failed, injections of Amgen's
    synthetic EPO can take up some of the slack. The drug is a lifesaver,
    so popular that the worldwide market for it is as high as $5 billion
    per year, and therein lies the problem: the cost of therapy is
    prohibitive. Three injections of EPO a week is a standard treatment,
    and patients who need this kind of therapy end up paying $7,000 to
    $9,000 a year. In poor countries struggling even to pay for HIV drugs
    like AZT, the added burden of paying for EPO to offset the side
    effects just isn't feasible.

    What if there was another way? What if the body could be instructed to
    produce more EPO on its own, to make up for that lost to kidney
    failure or AZT? That's the question University of Chicago professor
    Jeffrey Leiden asked himself in the mid-1990s. In 1997, Leiden and his
    colleagues performed the first animal study of EPO gene therapy,
    injecting lab monkeys and mice with a virus carrying an extra copy of
    the EPO gene. The virus penetrated a tiny proportion of the cells in
    the mice and monkeys and unloaded the gene copies in them. The cells
    began to produce extra EPO, causing the animals' bodies to create more
    red blood cells. In principle, this was no different from injecting
    extra copies of the ADA gene into Ashanti, except in this case the
    animals already had two working copies of the EPO gene. The one being
    inserted into some of their cells was a third copy; if the experiment
    worked, the animals' levels of EPO production would be boosted beyond
    the norm for their species.

    That's just what happened. After just a single injection, the animals
    began producing more EPO, and their red-blood-cell counts soared. The
    mice went from a hematocrit of 49 percent (meaning that 49 percent of
    their blood volume was red blood cells) to 81 percent. The monkeys
    went from 40 percent to 70 percent. At least two other biotech
    companies, Chiron and Ariad Gene Therapies, have produced similar
    results in baboons and monkeys, respectively.

    The increase in red-blood-cell count is impressive, but the real
    advantage of gene therapy is in the long-lasting effects. Doctors can
    produce an increase in red-blood-cell production in patients with
    injections of EPO itself-but the EPO injections have to be repeated
    three times a week. EPO gene therapy, on the other hand, could be
    administered just every few months, or even just once for the
    patient's entire lifetime.

    The research bears this out. In Leiden's original experiment, the mice
    each received just one shot, but showed higher red-blood-cell counts
    for a year. In the monkeys, the effects lasted for twelve weeks. The
    monkeys in the Ariad trial, which went through gene therapy more than
    four years ago, still show higher red-blood-cell counts today.

    This is a key difference between drug therapy and gene therapy. Drugs
    sent into the body have an effect for a while, but eventually are
    broken up or passed out. Gene therapy, on the other hand, gives the
    body the ability to manufacture the needed protein or enzyme or other
    chemical itself. The new genes can last for a few weeks or can become
    a permanent part of the patient's genome.

    The duration of the effect depends on the kind of gene vector used and
    where it delivers its payload of DNA. Almost all of the DNA you carry
    is located on twenty-three pairs of chromosomes that are inside the
    nuclei of your cells. The nucleus forms a protective barrier that
    shields your chromosomes from damage. It also contains sophisticated
    DNA repair mechanisms that patch up most of the damage that does

    Insertional gene vectors penetrate all the way into the nucleus of the
    cell and splice the genes they carry into the chromosomes. From that
    point on, the new genes get all the benefits your other genes enjoy.
    The new genes are shielded from most of the damage that can happen
    inside your cells. If the cell divides, the new genes get copied to
    the daughter cells, just like the rest of your DNA. Insertional
    vectors make more or less permanent changes to your genome. . . .

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