Sheila Rothman and David Rothman's The Pursuit of Perfection, David Healy's Let Them Eat Prozac, and the President's Council on Bioethics' Beyond Therapy
Elliott, Carl
IN THE PART OF South Carolina where I grew up, you can't travel too far without seeing a field or a patch of woods covered with a thick, green canopy of kudzu. Kudzu is a crawling vine native...
...But running through the report are signs of deep unease with the commodification of medicine, the erosion of professional values by a consumerist ethic, and the transformation of human identity itself into an instrument for human satisfaction...
...The Pursuit of Perfection shows just how closely the contemporary orthodoxy about genetics, with all its therapeutic promise and explanatory power, was paralleled by an earlier orthodoxy about endocrinology...
...There, kudzu grows like a pole bean on steroids...
...The vines extend themselves by a foot a day and will cover objects up to sters or The Day of the Triffids...
...The pharmaceutical companies have turned the SSRIs into blockbuster drugs, marketing them directly to patients with directtoconsumer ad campaigns, donating heavily to patient support groups, paying for conferences and hospital Grand Rounds, and funding a battery of "key opinion leaders" in psychiatry who unwittingly market the drugs on the lecture circuit by pushing the illnesses that the SSRIs are said to treat...
...He recruited twenty people from the university where he worked...
...The most disturbing part of the story Healy tells is not merely about the risks of SSRIs but about the efforts of the pharmaceutical industry to make sure those risks were not uncovered...
...For all this, Healy is still convinced that SSRIs have a legitimate place in clinical practice...
...IN 1966, Robert Wilson, a Brooklyn gynecologist, published a book called Feminine Forever...
...Both subjects became highly anxious, even aggressive, yet strangely detached from their own actions...
...Estrogen therapy doesn't change a woman," wrote Wilson...
...The largest clinical trial of hormone replacement therapy ever conducted was stopped prematurely, because hormones were proving to be so risky...
...But nobody seriously believes that SSRIs are prescribed only or even largely for serious depression anymore...
...But it does provide ample evidence that many regulators and industry insiders themselves have for years believed that SSRIs increased the risk of suicide...
...Wilson's book and all the magazine articles about estrogen, and they insist that I give them the pills," said one Miami gynecologist...
...Liberals, by contrast, tend to worry about commodification...
...Stem cells will cure untreatable illnesses...
...The skeptics come from both the left and the right...
...Some clinicians called the SSRIs "mood brighteners," but it was the psychiatrist Peter Kramer's term, "cosmetic psychopharmacology," that seemed to catch on...
...This orthodoxy did not so much suppress dissenters as ignore them...
...That offer was rescinded a year later after Healy gave a lecture in Toronto pointing out the link between SSRIs and suicide...
...Sometimes these consequences are simply the unforeseen side effects of a new technology, the way automobile exhaust helped bring about a hole in the ozone layer or kudzu overtook entire farms...
...As the Rothmans put it, "Women's magazines were not lining up to interview them, and medical journals were in no hurry to publish negative results...
...This is not because the issue is new: as Healy points out, the link between SSRIs and suicide has been debated in medical literature since 1990, when a group at Harvard published an article in the American Journal of Psychiatry outlining six cases of patients who became obsessed with suicide or attempted suicide after starting on Prozac...
...The story of Let Them Eat Prozac is yet another story of technology biting back: once a drug becomes this widely prescribed, the problem of rare but dangerous side effects becomes far more serious...
...THESE Two different political strands have come together in a report from the President's Council on Bioethics, Beyond Therapy: Biotechnology and the Pursuit of Happiness...
...Healy writes of journal articles ghostwritten by pharma-funded public relations companies and signed (for a fee) by respectable academics...
...When the merits of new, largely unknown technological advances are being argued— embryonic stem cells and nanotechnology at Harvard, kudzu control and air conditioning in South Carolina— the ethical debate often hinges on an effort to weigh up the potential risks and benefits of the technology...
...Sperling is certainly right about one thing: human enhancement is where the money is...
...Not that it contains anything approaching the kind of critique of industry power that is present in The Pursuit of Perfection, much less the muckraking Let Them Eat Prozac...
...But when the company applied for a patent for a new and improved version of the drug called Sepracor, it wrote that the new drug was needed because "fluoxetine produces a state of inner restlessness (akasthisia...
...In fact, it echoes the platform of the Green Party, which, for example, says that we must "live in ways that respect the integrity of natural systems...
...These people worry about the way technology frames our world and what it does to our sensibilities...
...Conservatives worry about the erosion of traditional values, human dignity, and BOOKS the "natural" order...
...DISSENT / Summer 2004 n 97 BOOKS Our current preoccupation with medical enhancement may be extreme, but as the Rothmans clearly demonstrate, it is not new...
...Given the effects of estrogen that women were reporting, this was no surprise...
...Synthetic growth hormone was initially introduced as a treatment for short children who were deficient in growth hormone, but last year the FDA approved its use for ordinary short children with no medical problems...
...For years Eli Lilly denied that Prozac had any relationship whatI 00 n DISSENT / Summer 2004 soever with akasthisia...
...Thus the risk of suicide on SSRIs should be compared not to the risk of suicide in hospital depression, suggests Healy, but to the risk of suicide in primary care depression...
...Some, like Botox and baldness drugs, don't masquerade at being anything other than enhancements...
...Grief, obsessiveness, shyness, alienation—all became fair game for medication with a selective serotonin reuptake inhibitor (SSRI) antidepressant...
...The report worries that the same impulses that have led Americans to spend a billion dollars a year on baldness remedies and have made antidepressants the most profitable prescription drugs in America may, if left unchecked, take us even further toward a world where even our children come to be seen as items to be shaped for our own personal fulfillment...
...96 n DISSENT / Summer 2004 When a treatment can be transformed into an enhancement, the task of weighing up risks and benefits becomes more complicated...
...But he alienated many former allies by testifying as an expert witness against the industry in a number of high-profile lawsuits brought by people whose relatives had committed suicide or homicide while taking antidepressants...
...In the case of this report, though, that would be a mistake...
...What is most striking about the study, however, is that it took so long to do it...
...Half of the subjects took Zoloft (sertraline), an SSRI manufactured by Pfizer, and half took another antidepressant with a different chemistry, reboxetine, whose makers had funded the study...
...But those researchers are often accompanied by a giddy crowd of venture capitalists, star-struck science journalists, canny pharmaceutical executives, and admiring bioethicists, many of whom have moved past hope and optimism to a place midway between progressive ideology and utopian fantasy...
...I am stronger, my vision has improved, and I have experienced an orgasm...
...The costly decision to introduce kudzu to the South is a good example of what Edward Tenner, the author of When Things Bite Back, calls "the revenge of unintended consequences...
...Part of this worry comes out of a deep distrust of corporate power...
...It wasn't just that they could help people who were clinically depressed...
...instead, he found two of his subjects having thoughts of suicide...
...For one thing, clinicians have been reporting suicides of patients on SSRIs who were not depressed—who were taking the drugs for other reasons...
...Within a year, it was available in seventeen countries...
...Men were happy, too...
...Many of these cases have wound up in court, sometimes with Healy testifying as an expert witness...
...Today's hype about genetic enhancement, cloning, and stem cells was preceded by a much earlier hype about hormones, secretions, and ductless glands...
...The more the better...
...Never in his life had Wilson held an academic post, but between April 1963 and August 1964 he published thirteen articles in medical journals arguing the benefits of estrogen...
...One began planning to hang herself from a beam in her bedroom...
...Seventy years later, that question about personality enhancement would emerge again—not with a hormone extract, but with a new class of psychoactive drugs...
...Wendell Berry has written that the whole point of the biotech industry is to make every farmer in the world dependent on corporations...
...Yet how those risks and benefits are balanced usually depends on the prediction of some hypothetical future scenario that, in the actual event, often turns out to have been shortsighted, misguided, or wrong...
...Another had a recurring dream where she slit her throat in bed and bled to death beside her partner...
...But over the next twenty years or so, the use of estrogens gradually crept back up...
...A 1974 study in the New England Journal of Medicine suggested that estrogen might be linked to a heightened risk of endometrial cancer...
...Its purpose is interpretive: to figure out exactly what the sources of moral unease with these new interventions might be, and whether we should be paying attention to them...
...The phrase "biotechnology" is a little misleading here...
...A psychopharmacologist by training, he worked closely with the pharmaceutical industry for most of his career...
...In his best-selling book, Listening to Prozac, Kramer worried about the consequences of using psychoactive 98 n DISSENT / Summer 2004 drugs not to make sick people well, but to make well people better than well...
...Estrogen, he predicted, would keep a woman vibrant and desirable into her later years...
...The SSRI antidepressants were first approved as a treatment for clinical depression, but they were soon prescribed to non-depressed people who wanted to be happier, more energetic, and more outgoing...
...But would we feel the same if the technology were intended merely to feed the hunger of the market, creating consumer demand in order to make profits for the biotechnology and pharmaceutical industries...
...Yet within a week after starting on Prozac, Forsyth had stabbed his wife fifteen times before fixing a kitchen knife to a chair and stabbing himself to death...
...These patients are treated by primary care doctors in outpatient clinics...
...The federal government paid farmers to plant it...
...but it is not an idea that should be dismissed out of hand...
...That could be accomplished with older generations of antidepressants...
...What Healy found was alarming...
...genetically modified foods will feed the developing world...
...therapeutic cloning will provide tissue for transplants...
...The result is Let Them Eat Prozac...
...By the end of the decade, the antidepressants had become the best-selling class of drugs in the United States...
...Three new books raise disturbing questions about the rush to bring enhancement drugs to market...
...Wilson became a recognizable figure in the popular media, telling women in magazines like Look and Vogue how estrogen would make them "grow visibly younger day by day...
...But medical orthodoxy about hormone replacement therapy was supported by a vast network of research grants and academic posts as well as an influential public relations industry...
...As long as the SSRIs were being prescribed for serious depression, their benefits clearly outweighed the risks...
...These cases were settled out of court...
...That scientific researchers themselves are narrowly optimistic is no great surprise...
...There is also the weird association between SSRIs and homiDISSENT / Summer 2004 . 99 BOOKS cide...
...It reads like an especially well-written scholarly book...
...Feminine Forever sold a hundred thousand copies in six months...
...Kudzu is a crawling vine native to Japan that was introduced to the South in the 1930s to prevent soil erosion...
...Even the current debate about psychoactive drugs has ample historical precedent...
...This is a lesson that Southern farmers would have done well to remember when they were planting kudzu in the thirties...
...Elizabeth Blackburn, the molecular biologist and council member whose term was not renewed by the Bush administration, has objected that the Council's reports imply that "medical research is not what God intended, that there is something unnatural about it...
...Properly understood, it merely suggests humility before what is given to us by biology: a recognition that the way we are built as human beings is the product of billions of years of evolutionary DISSENT / Summer 2004 0 BOOKS adaptation...
...of smear campaigns orchestrated by the industry to discredit its critics...
...John Sperling, the billionaire founder of the University of Phoenix, has devoted much of his vast fortune to biotech research aimed at radically extending the human lifespan...
...One became uncharacteristically aggressive, at one point jumping out of her car in traffic to manhandle a stranger shouting insults from the side of the road...
...But who could have looked at automobiles in 1915 and anticipatforty feet in height...
...By Healy's calculations, this means that primary care patients with depression would have a tenfold higher risk of suicide during their first month of treatment with an SSRI...
...Joseph Wesbecker was a fortysevenyear-old man with a history of depression who, after starting Prozac in September of 1989, took an AK-47 to the printing press in Kentucky where he worked...
...But they also include the larger social changes that a new technology brings about...
...Although Healy's study (which was published in a minor journal called Primary Care Psychiatry) was far too small to allow any serious conclusions to be drawn, it did add fuel to BOOKS a much larger and more volatile debate about the relationship between SSRIs and suicide...
...What neither the farmers nor the government anticipated was just how hardy kudzu would become in the humid Southern climate, where the soil is rich and kudzu has no natural enemies...
...Mainly a collection of personal stories from Wilson's practice, Feminine Forever reported the remarkable anti-aging effects of estrogen replacement therapy...
...Healy, a psychiatrist at the University of Wales, obtained industry funding to see how healthy volunteers with no history of mental illness would respond to antidepressants...
...And that figure is much lower—less than thirty suicides per one hundred thousand patient years...
...Beyond Therapy is utterly unlike any previous document issued by a presidential commission...
...The enthusiasm of clinicians for estrogen therapy was matched by a body of research data that, while more cautious than articles in the popular press, appeared to demonstrate that estrogen had a clear medical benefit...
...The question whether the SSRIs can trigger suicide is very difficult to parse because the condition they are often prescribed to treat—clinical depression—is so closely associated with suicide itself...
...The human organism is not something to be tinkered with lightly...
...But as Healy points out, that figure is for patients who were so severely depressed that they had to be hospitalized...
...Some Southerners claim that if you don't keep your windows closed at night, kudzu will swallow up your children while they sleep...
...The Rothmans quote a high school biology text from the 1920s asking students, "Do you think it would be a splendid achievement if someday the scientist could modify our dispositions by simply injecting an extract which contained the desired personal quality...
...and of the cozy relationship between the FDA and industry scientists...
...But none of this press has given us quite the glimpse into the corridors of industry power that Healy's book offers...
...Medical logic said estrogen was not so much a medical treatment as a replacement for what a women's body began failing to produce at menopause...
...One can see this especially in the environmentalist critique of agricultural biotechnology...
...In fact, one of the dangers of an earlier generation of antidepressants, the tricyclics, is that they are dangerous in overdose...
...THERE IS AN OLD debate about technology, which, in a time of dizzying technological change, has taken on new relevance...
...Instead, they felt detached, uninhibited, and impulsive...
...Wallace Laboratories marketed Milprem, a combination of estrogen and Miltown, while Roche produced a combination of estrogen and Librium...
...For example, Leon Kass, chair of the President's Council on Bioethics, has this to say about biotechnology: "If there is a case to be made against these activities—for individuals— we sense that it may have something to do with what is natural, or what is humanly dignified, or with the attitude that is properly respectful of what is naturally and dignifiedly human...
...This neglect was probably not intentional...
...Reboxetine is approved for use in Europe but not in the United States...
...According to Healy, the question of whether people on SSRIs have an increased risk of suicide depends critically on the population to which they are being compared...
...By the 1990s, it was estimated that about a third of post-menopausal women were taking hormone replacement therapy...
...What comes through in the report is not so much the suggestion that medical research is unnatural, but that the natural is something that deserves respect...
...On the other side are people who are skeptical about technology, especially about the way technology is shaping the kinds of human beings that we are becoming or might become...
...Akasthisia is a kind of extreme agitation and inner turmoil that ranges from restlessness and insomnia to anxiety bordering on panic...
...In July 2002 there came a dramatic reversal...
...Healy compares this effect of the drugs to a "medieval devil, something mindless and alien and capable of sucking any good there was out of someone...
...IN THE EARLY nineties, as Prozac and other antidepressants were just making their way into public consciousness, many psychiatrists noticed something a little unusual about these pills...
...The Rothmans also examine the development of synthetic human growth hormone for short children and the use of testosterone in aging men (as well as the strange history of liposuction, which turns out to be a surprisingly dangerous procedure...
...Not only do most herbicides fail to kill kudzu, at least one of them is said to make it grow even faster...
...One subject, looking at the beam from which she planned to hang herself, said she was drawn to it, controlled by it, and could imagine her family finding her body the next day—yet she just didn't care...
...This was the question that David Healy set out to answer in the late nineties...
...As the years passed, Healy transformed himself into the drug industry's worst nightmare: a psychopharmacologist on an ideological mission...
...Manufacturers began combining estrogen with progesterone, and the name was changed from "estrogen replacement therapy" to "hormone replacement therapy...
...If a depressed patient commits suicide while on an SSRI, is it because of the illness or the drug...
...The trial was supposed to run until 2005, but when the data safety and monitoring board analyzed the data in 2002, it found that health outcomes were so poor for women on hormone replacement therapy that the board could not in good conscience allow women in the study to keep taking it...
...It is not uncommon to see large trees, telephone poles, barns, abandoned tractors, or rusting cars completely enveloped by kudzu vines...
...To anyone who has followed that debate, Healy is a familiar figure...
...I am 100 percent for human enhancement," Sperling told Wired magazine in February...
...It offers no guidelines, no regulations, no recommendations...
...They've all read Dr...
...The conventional figure for the risk of suicide in depression is a 15 percent lifetime risk, or six hundred suicides per one hundred thousand patient years...
...But could the SSRIs really do what Kramer and others had suggested...
...But in 2001, a Wyoming court returned a guilty verdict against Glaxo SmithKline in the case of Donald Schell, a sixty-year-old man taking Paxil who shot his wife, his daughter, and his granddaughter before shooting himself...
...In fact, the term "report" is misleading as well...
...Yet it does not quite hit the mark...
...The problem is one of rare but very dangerous side effects...
...It is worth remembering that the current council has no apparent ties to the pharmaceutical or biotech industries, whereas its predecessor, appointed by the Clinton administration, was chaired by a member of the Dow Chemicals advisory board and included the co-founder of NeuralStem Biopharmaceuticals Ltd, the scientific director of Perlagen Sciences, and the chief business officer of Millenium Pharmaceuticals...
...They are not concerned about social change per se but rather about social change guided solely by the market...
...If we alter the human genome or the way humans reproduce, they argue, we will alter something essential to what humans are...
...often these are enthusiasts who see technology as the solution to every imaginable problem, including the fact that every human life has to end...
...IT IS AN alarming book...
...She said that she had decided to throw herself in front of a car, and it was only by virtue of a chance phone call that she was stopped...
...He had expected to find some ordinary people becoming better than well...
...However, most enhancement technologies begin as treatments for real medical problems and are later transformed into enhancements by the market...
...of industry executives suppressing research data and withholding crucial information from regulators...
...The SSRIs are now prescribed for a much wider range of patients, most of whom do not have severe depression...
...William Forsyth, a prosperous businessman in his sixties who had retired to Hawaii, had never been hospitalized for depression in his life...
...Another said, "It is a miracle to find myself at the age of 71 enjoying better health after several years of misery...
...I)t keeps her from changing, that is, from suffering 'living decay...
...For many on the left, the fact that the President's Council on Bioethics was appointed by George W. Bush is enough to discredit it (and given Bush's record on science policy, it is hard to blame them...
...Many women began asking their gynecoloBOOKS gists for estrogen...
...Ayerst ran ads with the tag line, "He is suffering from menopause because of her...
...One described the drug she was taking as a "chill pill...
...Wilson had given estrogen to more than five thousand women to protect them from withering away at menopause, a period of life that, as he put it, turns a woman into a "dull-minded but sharptongued caricature of her former self...
...In fact, the council has bent over backward to emphasize the therapeutic value of most of the interventions it discusses...
...When this study was followed by a warning from the Food and Drug Administration, the number of prescriptions for estrogen replacement therapy dropped from twentyseven million in 1975 to fourteen million in 1980...
...One early series of case histories from Yale reported children being treated for obsessive compulsive disorder who became suicidal on SSRIs...
...Since that time there have been dozens of journal articles arguing both sides of the issue, two FDA hearings (one cleared the SSRIs, the other is still ongoing), a number of muckraking journalistic investigations, and perhaps most controversially, a series of highprofile court cases...
...Two years earlier the makers of Premarin, Enovid, and Provera had given Wilson a $31,350 "research grant" to establish an anti-aging foundation...
...As the Rothmans summarize the trial: "Over one year, 10,000 women taking estrogen plus progestin compared to placebo would experience 7 more coronary artery disease events, 8 more strokes, 8 more pulmonary blood clots, and 8 more invasive breast cancers . . . " The study stunned many doctors and was widely reported in the popular press, including cover stories in Time and Newsweek...
...He killed eight people and wounded twelve more before killing himself...
...Many of us would be willing to risk a radical new technology if it might cure a dangerous illness or feed hungry people in the developing world...
...According to a 2001 study by the National Institutes of Health Care Management and Research, the antidepressants were the best-selling class of drugs in America...
...On one side of the debate are people who are impressed by the possibilities of human advance...
...Humility before what is naturally given to us is not the sole province of the political right...
...In 1999, he was offered a post as director of the Mood and Anxiety Disorders Program at the Center for Addiction and Mental Health, an academic hospital at the University of Toronto...
...The manufacturers of estrogen replacement therapy were fully aware of how valuable a commodity Wilson was, as Sheila and David Rothman note in their perceptive and accessible history of medical enhancement, The Pursuit of Perfection...
...Menrium treats the menopausal symptoms that bother him the most," said the advertisements from Roche...
...Their fear is that the market will bring us a world where we are preoccupied with efficiency and sales and value-added products, where everything has been transformed into an item for our consumption or entertainment...
...It took no great feat of imagination to see that automobiles could cause pollution...
...Not that there weren't occasional warning signs...
...CARL Ewan- teaches in the Center for Bioethics at the University of Minnesota and is the author of Better Than Well: American Medicine Meets the American Dream...
...Advertising shifted away from hormones as anti-aging therapy and toward hormones as preventive medicine, based on data suggesting that hormones helped prevent cardiovascular disease and osteoporosis...
...Beyond Therapy is the product of a conservative council, but this may be a kind of conservatism that many liberals can live with...
...In fact, the pharmaceutical industry often advertised estrogen to doctors in a way that emphasized its benefits for men...
...Because menopause was thought to be associated with depression and anxiety, some pharmaceutical companies bundled estrogen into a single pill alongside a "minor tranquilizer...
...They object to some varieties of biotechnology on grounds of human nature...
...The new antidepressants seemed to help people with conditions that, by most definitions, would not have counted as any kind of mental disorder at all...
...Much of today's enthusiasm for biotechnology depends upon a narrow, highly optimistic view of what it will eventually accomplish...
...Here is an internal memo from Lilly, the manufacturer of Prozac, on the comparison of fluoxetine (Prozac) with imipramine, a tricyclic antidepressant: "The incidence rate [of suicidal acts] under fluoxetine . . . is 5.6 times higher than under the other active medication imipramine...
...it is written in a graceful style that could hardly be more different from the bureaucratic jargon of a government document...
...Unfortunately, although Let Them Eat Prozac includes complicated discussions of the data on suicide, it does little to reduce the complexity...
...There have been signs from the start that the SSRIs were different from earlier antidepressants...
...His "Wilson Research Foundation" arranged lectures and distributed pamphlets promoting estrogen therapy, and even kept a list of doctors who prescribed estrogen...
...Healy believes that at least some of the suicide and homicide can be explained by a side effect of SSRIs termed "akasthisia...
...Neither felt any concern for the family members they would leave behind if they killed themselves...
...After two and a half weeks, I awoke one morning with a sense of well-being I'd never experienced before," said one...
...While it will never be mistaken for an endorsement of medical enhancement, neither is it a straightforward condemnation...
...It all made perfect sense...
...Psychiatrists were often reluctant to give patients too large a supply, for fear that they would kill themselves with the drugs...
...Enhancement technologies are among the most profitable medical interventions available...
...That suggestion can be employed for dangerous purposes, of course, for many well-rehearsed reasons...
...Hormone replacement therapy is only one example...
...Plastic surgery was initially developed as a way of reconstructing tissue damage from trauma or illness, but surgeons soon began applying the same techniques for cosmetic purposes...
...The plan was to recruit sixty-five thousand women to take hormone therapies and compare them to a hundred thousand controls...
...His participation in lawsuits has given him unprecedented access to internal industry data, unpublished clinical trials, and confidential executive memos...
...the report is not so much about biotechnology as about medical enhancements, from performance-enhancing drugs and cosmetic psychopharmacology to anti-aging therapies and stimulants for children...
...In 1993 the National Institutes of Health had started the Women's Health Initiative (WHI), one piece of which was a large study of hormone replacement therapy...
...When German regulators rejected Lilly's application to market Prozac in Germany in the 1980s, they pointed especially to akasthisia, saying that "an increase in agitating effects occurs earlier than mood elevating effect and therefore an increased risk of suicide exists...
...Yet, oddly enough for patients who were suicidal, neither patient was clinically depressed...
...Enterprising Southerners sometimes say that if you could just harness kudzu for a commercial purpose you could make a mint, but the fact is that you'd be more likely to make a B-grade horror movie, like The Monolith MonDISSENT / Summer 2004 • 95 BOOKS ed NASCAR dads, the Mall of America, and drive-through liquor stores...
...That argument has been echoed by other critics...
...Whether the WHI findings will stand up to further scrutiny remains to be seen...
...In a market-driven health care system, making sick people well is often not as profitable as making well people taller, stronger, happier, and better looking...
Vol. 51 • July 2004 • No. 3
