The Future of Designer Babies

The idea of the perfect human has been around a long time. From Tao Te Ching to Nietsche and Galton, many great minds have described certain desirable and non-desirable qualities of man.

Until recently, all human reproduction resulted from sexual intercourse, and couples had to be prepared for the luck of the natural lottery. Now powerful new technologies are changing the reproductive landscape and challenging basic notions about procreation, parenthood, family, and children. Recent scientific discoveries within the field of human genetics and reproductive technologies have revitalized many timeless thoughts about human perfection.

designerbabyPreimplantation genetic diagnosis

PGD, or preimplantation genetic diagnosis marries the recent advances in molecular genetics and assisted reproductive technology. Preimplantation genetic diagnosis enables physicians to identify genetic diseases in the embryo, prior to implantation, before the pregnancy is established. PGD obviate the need for screening during a pregnancy and hence prevent the physical and psychological trauma associated with possible termination.

Every person or couple contemplating children wants healthy offspring, yet knows that offspring characteristics cannot be guaranteed in advance. New screening and selection technologies are now changing this situation. Prenatal diagnosis is occurring earlier and for a wider range of conditions. In the future techniques to alter genes for both therapeutic and nontherapeutic purposes will become available. Whether couples may or must use these techniques raises important questions about the scope of procreative liberty.

Selection techniques

Selection techniques now rely on carrier or prenatal screening to identify persons at risk for having handicapped offspring. Today carrier screening mostly occurs in high-risk subgroups, but will eventually touch most couples, as carrier tests for cystic fibrosis and other common conditions become routinely available. Couples aware of their carrier status may then decide not to reproduce, use donor gametes, or adopt. They may also seek prenatal diagnosis and terminate pregnancy if they do conceive. As the ability to diagnose more genetic conditions earlier and less invasively grows, prenatal screening will eventually affect most pregnancies. Chorion villus sampling, which occurs at 10–12 weeks of pregnancy, is replacing amniocentesis at 14–18 weeks as the prenatal diagnostic method of choice for women at risk for chromosomal and genetic conditions.

Sixty-five percent of pregnancies in the United States are now screened for alpha fetal protein, an indicator for neural tube defects such as spina bifida and anencephaly. 1 As tests to identify fetal cells in maternal blood are perfected, the genetic condition of every fetus will be diagnosable at 7–8 weeks by a simple blood test. It is likely that such tests will become a routine part of prenatal care, followed often by pregnancy termination when the test is positive. Genetic diagnosis of preimplantation embryos, now occurring in clinical experiments, will also be available. (See “Children of Choice: Freedom and the New Reproductive Technologies”, Assisted Reproduction.)

Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos in 1968. In humans, PGD was developed in the United Kingdom in the mid 1980s as an alternative to current prenatal diagnoses. PGD is presently the only option available for avoiding a high risk of having a child affected with a genetic disease without facing the dilemma of pregnancy termination following positive prenatal diagnosis. In 1989 in London, Handyside and colleagues reported the first unaffected child born following PGD performed for an X-linked disorder. As of May 2001, more than 3000 PGD clinical cycles have been reported. These cycles were performed at more than 40 centers around the world, and almost 700 children have been born, thus demonstrating the reliability and safety of the procedure.

In Vitro Fertilization (IVF)

Couples who elect to have PGD undergo an in vitro fertilization (IVF) embryos are formed as usual in the laboratory. Embryos are then biopsied with very fine glass needles and tools under microscopic observation and control to obtain one or two sample cells (blastomeres) for genetic analysis using either specialized DNA amplification or fluorescent hybridization systems. Embryos whose biopsy results are normal are then available for immediate transfer into the uterus, with additional embryos (if available) frozen for subsequent transfer. Experiences with PGD in humans have documented the safety and efficacy of this technology for preventing genetic disorders and producing the births of normal children.

PGD was first used in the early 1990s to screen out embryos carrying the mutations that cause inherited diseases such as Duchenne’s muscular dystrophy. The clinics offering it as a way of improving pregnancy rates look instead at whether the right number of chromosomes is present. Having extra chromosomes or fewer than normal is known as aneuploidy, and most aneuploid embryos die early in pregnancy (the notable exception being Down’s syndrome). The older a women, the more likely aneuploidy is: while about one per cent of embryos from women in their 20s and early 30s are aneuploid, in women over 40 the figure is over 50 per cent.

Many of these embryos look normal on visual inspection, which is why in the mid-1990s researchers suggested using PGD to spot aneuploid embryos. In theory, this should increase a woman’s chances of getting pregnant and having a healthy baby, because only normal embryos will be implanted. This is the basis on which a growing number of clinics are offering this form of PGD, and ever more patients are demanding it, despite a price tag of up to ,000 per IVF cycle.

Current uses of PGD range from sex selection (family balancing or as a stem cell source) and ensuring that inherited diseases are avoided. PGD can be offered for 3 major groups of disease, including (1) sex-linked disorders, (2) single gene defects, and (3) chromosomal disorders. Down Syndrome, X-linked diseases (Duchenne Muscular Dystrophy), chromosomal translocation, Spinal Muscular Atrophy, Tay Sachs Disease, Hemophilia, Huntington Disease and Cystic Fibrosis and many other genetic diseases can be avoided using PGD.

Demographic Consequences of Reproductive Technologies

The reasons for selecting the sex of your child vary. The Chineses one-child policy has caused a major market for sex selection services. The effects of such policies on the demographic characteristics of the population cause controversy. Since the male population is associated with higher income and living standards many opt for male children. The resulting male/female imbalanced ratio could cause massive emmigration of Chinese males looking for females elsewhere.

In the West potential parents choose the sex of the children based on so-called “family balancing” rethoric. Ensuring that you have both male and female kids is by many considered vanity. Parents have used sex-selection to produce donor kids for their existing kids with an organ-disorder. Many of these advances become precedent for future applications of reproductive technologies.

People with inherited diseases often learn to live with the disability and accept imperfect genetics as a part of life. Blind parents have chosen to ensure that their offspring also will be blind. Accepting the genetic diversity of mankind is essential to an ethical approach to reproductive technologies. Accepting differences in humans doesn’t bother most people when they try to ensure healthy kids. The slippery slope of reproductive technologies starts where “ensuring healthy kids” ends and “human enhancement” begins.

From the Oneida Community to Transhumanism

John Humphrey Noyes lead the human selective breeding programme taking place in a North American bible communist community, Oneida, between 1869 and 1879. It was probably the first such breeding experiment of the modern era, and for this reason, we might expect it to have been influential for the subsequent eugenics movements. Although it attracted much attention in its day, its longer-term influence seems to have been surprisingly slight, largely because its specific context meant that it was not a model that provided an acceptable way to reach eugenics goals. (See “A Nineteenth-Century Experiment in Human Selective Breeding”, Nature 2004)

The idea of the Oneida Community was to breed superior children by encouraging the mating of the healthiest, most intelligent males and females. After much debate, Noyes had become convinced that “a scientific breeding program could be adapted to the needs of the Oneida community” (Kephart and Zellner, p.84). This practice of stirpiculture, then, can be regarded as a derivation of the principle of eugenics — attempts to improve hereditary qualities; selective breeding. Although no such term was known at the time of the Community, this is exactly the concept that Noyes and his people adopted. Only certain people were allowed to become parents, and these were hand-picked by a special committee. Nearly ninety percent of Community babies born in an eleven-year span were carefully planned by such a committee. During the time of the program, no defective children were born, and no mothers died as a result of childbirth. (See “The Oneida Community”, Religious Movements).

Similar ideas are presented in Galton’s “The University of Kantsaywhere”. Pearson (1930, pp. 411 ff.) has published the surviving fragments of Kantsaywhere, a short utopian novel Galton wrote in 1910, just before he died. In this fantasy, a young Englishman finds himself in “Kantsaywhere,” a country that has instituted highly effective eugenic practices. Preeminent among these are two examinations administered by the local “Eugenic College.” First is a largely medical “Pass Examination” which must be taken by everyone and passed to gain State permission to marry and have children. A sufficiently high pass on this entitles one to compete in the further “Honours Examination,” with four equally weighted parts measuring a) medical fitness; b) ancestral quality; c) anthropometric quality; and d) aesthetic and literary skill. The anthropometric tests in this examination are exactly like those from the South Kensington Laboratory. The “aesthetic and literary” section includes assessment of aesthetic judgment, as well as more standard examination tasks such as essay writing.

To imagine a modern Oneida Community or University of Kantsaywhere is a challenging task. People today are used to genetic tests and family planning. The basis for a new eugenics movemement should be individual freedom of choice. The development of more powerful reproductive technologies speed up the possibilites of human enhancement. If parents were given the option to select for cognitive capabilities, height, hair and eye color, strength and other phenotypical features – do you think they would choose not to use it?

Transhumanists promote the view that human enhancement technologies should be made widely available, and that individuals should have broad discretion over which of these technologies to apply to themselves (morphological freedom), and that parents should normally get to decide which reproductive technologies to use when having children (reproductive freedom). Transhumanists believe that, while there are hazards that need to be identified and avoided, human enhancement technologies will offer enormous potential for deeply valuable and humanly beneficial uses. Ultimately, it is possible that such enhancements may make us, or our descendants, “posthuman”, beings who may have indefinite health-spans, much greater intellectual faculties than any current human being – and perhaps entirely new sensibilities or modalities – as well as the ability to control their own emotions. (See “In Defense of Posthuman Dignity”, Nick Bostrom)

Death as Curable Disease

Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus accumulates. This accumulating damage ultimately drives age-related degeneration. Interventions can be designed at all three stages. However, intervention in metabolism can only modestly postpone pathology, because production of toxins is so intrinsic a property of metabolic processes that greatly reducing that production would entail fundamental redesign of those processes. Similarly, intervention in pathology is a “losing battle” if the damage that drives it is accumulating unabated. By contrast, intervention to remove the accumulating damage would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely. We survey the major categories of such damage and the ways in which, with current or foreseeable biotechnology, they could be reversed. Such ways exist in all cases, implying that indefinite postponement of aging–which we term “engineered negligible senescence”–may be within sight. Given the major demographic consequences if it came about, this possibility merits urgent debate. (See “Critiquing the immutability of human aging”, PubMed)

Understanding and manipulating the genetics of aging would also cause enormous consequences. If aging is caused by a set of genes and these genes were to be found the ability to re-set the “death-clock” would be very tempting. Gene therapy on adults or genetically modified kids with expected life spans of, say, 200 would cause incredible consequences on pensions, insurance and other vital parameters of modern life.

Stem Cells and Gene Therapy

Human stem cell lines from genetically flawed human embryos have been created by US scientists. The team that produced the mutant lines at the Reproductive Genetics Institute in Chicago believes the cell lines will help shed light on genetic diseases and could be used to test new treatments.

The team is the first to announce the creation of human embryonic stem cell (ESC) lines from embryos with specific genetic diseases, However, other groups around the world have also been racing to develop mutant ESCs, one group in the UK has already created a line for cystic fibrosis.

The US cell lines were produced from embryos left over from in-vitro fertilisation procedures. The embryos were discarded after genetic screening revealed they had defects. The immortal lines generated include several for diseases caused by single gene mutations, including some muscle and blood disorders. (See “Mutant human stem cell lines created”, New Scientist)

Establishment of embryonic stem cells derived from mutant embryos provides new opportunities for studying and treatment of human genetic disorders, gene therapy, pharmaceutical development and toxicological screening technologies. Stephen Minger, director of the stem cell biology laboratory at King’s College London, UK, agrees that such mutant ESCs could help scientists better understand certain diseases and test treatments. But he adds each line will have “greater or lesser merit” depending on the disease.

Saving the World with Genetic Enhancement

As biomedical science progresses, ever more effective medical technologies are devised for the treatment of illnesses, and this is, of course, a good thing. But how do we feel about the use of such technologies by people who are healthy to start with in order to become more than healthy? Many such enhancement technologies are already widely available. Cosmetic surgery is used for aesthetic enhancement of the body, beta-blockers such as Propranolol by musicians to block the physical symptoms of performance nerves, thereby enhancing the quality of their playing, and the antidepressant Prozac is used as an agent of what Peter Kramer has called cosmetic psychopharmacology, or alteration of personality, to make people less shy, less compulsive, more confident. We have to assume that with time more enhancement technologies will become available – many more, employing surgery, genetics, pharmacology, and heaven knows what else, directed in particular at cognitive function and longevity. (See “Enhancing human Traits: Ethical and Social Implications”, Nature 1999)

Further advances within biotechnology, gene therapy, genetic engineering, stem cells and PGD will cause massive demographic changes. People would live longer, healthier and more intelligence lives. People would be able to have multiple educations and multiple careers and would thus become more knowledgeable and experienced than contemporary humans. This will lead to better problem solving and more efficient organizations, and subsequently the possibilty of ending war, hunger and diseases. The final reasonable exit left for mankind out of the mess we call earth, is through genetic enhancement.

When the genetics of intelligence (g, or General Intelligence) is understood parents would face the dilemma of choosing to live with a brighter kid than themselves. The difference between “high-investement parenting” and “high-intelligence parenting” could change. Society would have to undergo a dramatic change of the perception of human qualitities. New lines of work would ensue after a generation of high-intelligence parenting. New types of schools and new communities would naturally follow in the wake of widespread genetic enhancement of humans.

A new debate and a subsequent new ethics for the evolution of humans is of critical importance for the survival of modern civilization.

stock-designer-babiesExcerpts from “Redesigning Humans: Choosing our genes, changing our future” by Gregory Stock
Thanks to Matt Nuenke for comments and transcription.

—In the past year, I have debated various aspects of the advanced reproductive technologies Redesigning Humans predicts with those who strongly oppose them. Given my belief that such technologies are inevitable (indeed, the subtitle of the hardcover edition of this book was Our Inevitable Genetic Future), I often wondered whether those who advocated banning them really thought this could stop them. Most such individuals I’ve asked have readily admitted, at least in private, that these innovations will eventually arrive, but they still think it’s important to try to block them.

013—Even the European position against human germline engineering itself may be thawing. In December 2002, building on the September 2000 AAAS meeting mentioned in chapter 8, the International Forum for Biophilosophy met in Brussels to consider the ethics of inheritable genetic modifications (IGM) in humans. The members concluded, “No interpretation of human dignity has been identified that stands in the way of the development of IGM. The so-called right to be born with a human genome that has not been modified by artificial means was not recognized here as being a clear and a compelling right.” They then commented, “Knowing that IGM will provide a variety of possibilities, ranging from purely therapeutic to pure enhancement, an urgent need exists to study the ethical aspects of access.” Such a dramatic and rapid shift from the Council of Europe’s harsh pronouncements in 1997, which opposed the development of IGM altogether, surprised me.

The morality of destroying or modifying embryos is central to discussions of all germinal choice technologies. So far, this issue has surfaced primarily in debates about therapeutic cloning or the use of human embryos for medical research, but neither germline engineering nor IVF can escape this concern, since they, too, destroy embryos. I did not deal with this at length in the hardcover edition, because I felt that the debate so hinged on deeply held philosophical and religious beliefs about the personhood of early-stage embryos — an arcane dispute in which discussion changes few minds. But in the past year I’ve been asked about the issue so often that I will now offer a few thoughts on it.

Critics of embryo research frequently claim that an embryo is a nascent person and that such research must be banned because it is tantamount to human experimentation. Proponents, on the other hand, insist that a mere speck of undifferentiated cells deserves no special protection, regardless of its potential to become a person — or persons, for that matter, since for about two weeks an embryo can split into two or more independent embryos, which is how identical twins arise. In fact, two separate embryos, apparently destined to become fraternal twins, sometimes bump together in the fallopian tubes and fuse into a single embryo, forming one individual with patches of cells from both lineages. In essence, such a person is two genetically distinct people melded into one. To avoid such conundrums, the term “pre-embryo” is used in Britain to describe an embryo during those first two weeks of relative plasticity, and medical research and embryonic stem cell work is allowed only during this period. But to invest either pre-embryos or embryos in a petri dish with personhood, based on their “potential” to develop into a human being, too readily dismisses the realities of the path from conception to birth.

Christian theologians may assert that with the magical meeting of sperm and egg a new human life has been created and infused with a soul, and that after that union, anything we do to interfere with the natural unfolding of an embryo’s potential is wrong — from extracting it from a woman’s womb to pouring it down the drain. But a united sperm and egg are hardly sufficient to create a new life. A third element, one we often take for granted, is needed: a mother. Without attachment to a warm and nurturing womb, no embryo has ever developed into a child. Outside the body, no embryo can develop for more than a few days. Some IVF labs can coax development as far as a tiny dot of a few hundred cells, but beyond that, the signaling and nutritional demands are too complex. Without the mother’s magic, this little fleck of cells will die, just like virtually all eggs and sperm. Someday science may construct an artificial womb capable of taking over the mother’s role, but such a development is far beyond our present understanding of the life-giving dance of mother and developing fetus.

In my view, those who argue that personhood resides in some disembodied cluster of cells — outside the unbroken cycle of intimate connection between mother and child extending back to the first glimmerings of human life — are ignoring this biological continuity. To argue that a woman is simply the instrument by which a life is shepherded to its childhood seems an odd assertion, especially for those who hold dear the value of family.

It is reasonable to debate about when a growing embryo nestled in a mother’s womb becomes invested with full individual rights that may trump even the welfare of the mother. Some will maintain that those rights are immediate, others that they come at birth. But to infuse personhood into a speck of cells in a petri dish, cells that by themselves will never be anything more, is largely dogma. In my opinion, to use such an abstract assertion to block biomedical research directed at real people who have real diseases and real suffering shows disregard, not respect, for human life and dignity.

004—Yet the road to our eventual disappearance might be paved not by humanity’s failure but by its success. Progressive self-transformation could change our descendants into something sufficiently different from our present selves to not be human in the sense we use the term now. Such an occurrence would more aptly be termed a pseudoextinction, since it would not end our lineage. Unlike the saber-toothed tiger and other large mammals that left no descendants when our ancestors drove them to extinction, Homo sapiens would spawn its own successors by fast-forwarding its evolution.

005—Many bioethicists do not share my perspective on where we are heading. They imagine that our technology might become potent enough to alter us, but that we will turn away from it and reject human enhancement. But the reshaping of human genetics and biology does not hinge on some cadre of demonic researchers hidden away in a lab in Argentina trying to pick up where Hitler left off. The coming possibilities will be the inadvertent spin-off of mainstream research that virtually everyone supports. Infertility, for example, is a source of deep pain for millions of couples. Researchers and clinicians working on in vitro fertilization (IVF) don’t think much about future human evolution, but nonetheless are building a foundation of expertise in conceiving, handling, testing, and implanting human embryos, and this will one day be the basis for the manipulation of the human species. Already, we are seeing attempts to apply this knowledge in highly controversial ways: as premature as today’s efforts to clone humans may be, they would be the flimsiest of fantasies if they could not draw on decades of work on human IVF.

Similarly, in early 2001 more than five hundred gene-therapy trials were under way or in review throughout the world. The researchers are trying to cure real people suffering from real diseases and are no more interested in the future of human evolution than the IVF researchers. But their progress toward inserting genes into adult cells will be one more piece of the foundation for manipulating human embryos.

008—Professional sports offers a preview of the spread of enhancement technology into other arenas. Sports may carry stronger incentives to cheat, and thus push athletes toward greater health risks, but the non-sporting world is not so different. A person working two jobs feels under pressure to produce, and so does a student taking a test or someone suffering the effects of growing old. When safe, reliable metabolic and physiological enhancers exist, the public will want them, even if they are illegal. To block their use will be far more daunting than today’s war on drugs. An anti-drug commercial proclaiming “Dope is for dopes!” or one showing a frying egg with the caption “Your brain on drugs” would not persuade anyone to stop using a safe memory enhancer.

Aesthetic surgery is another budding field for enhancement. When we try to improve our appearance, the personal stakes are high because our looks are always with us. Knowing that the photographs of beautiful models in magazines are airbrushed does not make us any less self-conscious if we believe we have a smile too gummy, skin too droopy, breasts too small, a nose too big, a head too bald, or any other such “defects.” Surgery to correct these non-medical problems has been growing rapidly and spreading to an ever-younger clientele. Public approval of aesthetic surgery has climbed some 50 percent in the past decade in the United States. We may not be modifying our genes yet, but we are ever more willing to resort to surgery to hold back the most obvious (and superficial) manifestations of aging, or even simply to remodel our bodies. Nor is this only for the wealthy. In 1994, when the median income in the United States was around ,000, two thirds of the 400,000 aesthetic surgeries were performed on those with a family income under ,000, and health insurance rarely covered the procedures. Older women who have subjected themselves to numerous face-lifts but can no longer stave off the signs of aging are not a rarity. But the tragedy is not so much that these women fight so hard to deny the years of visible decline, but that their struggle against life’s natural ebb ultimately must fail. If such a decline were not inevitable, many people would eagerly embrace pharmaceutical or genetic interventions to retard aging.

The desire to triumph over our own mortality is an ancient dream, but it hardly stands alone. Whether we look at today’s manipulations of our bodies by face-lifts, tattoos, pierced ears, or erythropoietin, the same message rings loud and clear: if medicine one day enables us to manipulate our biology in appealing ways, many of us will do so — even if the benefits are dubious and the risks not insignificant. To most people, the earliest adopters of these technologies will seem reckless or crazy, but are they so different from the daredevil test pilots of jet aircraft in the 1950s? Virtually by definition, early users believe that the possible gains from their bravado justify the risks. Otherwise, they would wait for flawed procedures to be discarded, for technical glitches to be worked through, for interventions to become safer and more predictable.

In truth, as long as people compete with one another for money, status, and mates, as long as they look for ways to display their worth and uniqueness, they will look for an edge for themselves and their children.

People will make mistakes with these biological manipulations. People will abuse them. People will worry about them. But as much could be said about any potent new development. No governmental body will wave some legislative wand and make advanced genetic and reproductive technologies go away, and we would be foolish to want this. Our collective challenge is not to figure out how to block these developments, but how best to realize their benefits while minimizing our risks and safeguarding our rights and freedoms. This will not be easy.

Our history is not a tale of self-restraint. Ten thousand years ago, when humans first crossed the Bering Strait to enter the Americas, they found huge herds of mammoths and other large mammals. In short order, these Clovis peoples, named for the archaeological site in New Mexico where their tools were first identified, used their skill and weaponry to drive them to extinction. This was no aberration: the arrival of humans in Australia, New Zealand, Madagascar, Hawaii, and Easter Island brought the same slaughter of wildlife. We may like to believe that primitive peoples lived in balance with nature, but when they entered new lands, they reshaped them in profound, often destructive ways. Jared Diamond, a professor of physiology at the UCLA School of Medicine and an expert on how geography and environment have affected human evolution, has tried to reconcile this typical pattern with the rare instances in which destruction did not occur. He writes that while “small, long-established egalitarian societies can evolve conservationist practices, because they’ve had plenty of time to get to know their local environment and to perceive their own self-interest,” these practices do not occur when a people suddenly colonizes an unfamiliar environment or acquires a potent new technology.

Our technology is evolving so rapidly that by the time we begin to adjust to one development, another is already surpassing it. The answer would seem to be to slow down and devise the best course in advance, but that notion is a mirage.

012—Watson’s simple question, “If we could make better humans . . . why shouldn’t we?” cuts to the heart of the controversy about human genetic enhancement. Worries about the procedure’s feasibility or safety miss the point. No serious scientists advocate manipulating human genetics until such interventions are safe and reliable.

Why all the fuss, then? Opinions may differ about what risks are acceptable, but virtually every physician agrees that any procedure needs to be safe, and that any potential benefit needs to be weighed against the risks. Moreover, few prospective parents would seek even a moderately risky genetic enhancement for their child unless it was extremely beneficial, relatively safe, and unobtainable in an easier way. Actually, some critics, like Leon Kass, a well-known bioethicist at the University of Chicago who has long opposed such potential interventions, aren’t worried that this technology will fail, but that it will succeed, and succeed gloriously.

013—The coming advances will challenge our fundamental notions about the rhythms and meaning of life. Today, the “natural” setting for the vast majority of humans, especially in the economically developed world, bears no resemblance to the stomping grounds of our primitive ancestors, and nothing suggests that we will be any more hesitant about “improving” our own biology than we were about “improving” our environment. The technological powers we have hitherto used so effectively to remake our world are now potent and precise enough for us to turn them on ourselves. Breakthroughs in the matrix-like arrays called DNA chips, which may soon read thirty thousand genes at a pop; in artificial chromosomes, which now divide as stably as their naturally occurring cousins; and in bioinformatics, the use of computer-driven methodologies to decipher our genomes — all are paving the way to human genetic engineering and the beginnings of human biological design.

014—Difficult ethical issues about our use of genetic and reproductive technologies have already begun to emerge. It is illegal in much of the world to test fetal gender for the purpose of sex selection, but the practice is commonplace. A study in Bombay reported that an astounding 7,997 out of 8,000 aborted fetuses were female, and in South Korea such abortions have become so widespread that some 65 percent of third-born children are boys, presumably because couples are unwilling to have yet a third girl. Nor is there any consensus among physicians about sex selection. In a recent poll, only 32 percent of doctors in the United States thought the practice should be illegal. Support for a ban ranged from 100 percent in Portugal to 22 percent in China. Although we may be uncomfortable with the idea of a woman aborting her fetus because of its gender, a culture that allows abortion at a woman’s sole discretion would require a major contortion to ban this sex selection.

Clearly, these technologies will be virtually impossible to control. As long as abortion and prenatal tests are available, parents who feel strongly about the sex of their child will use these tools. Such practices are nothing new. In nineteenth-century India, the British tried to stop female infanticide among high-caste Indians and failed. Modern technology, at least in India, may merely have substituted abortion for infanticide.

034—In light of the major differences we have created between poodles and Great Danes in a few thousand years, using the primitive tools of animal breeding, our own self-selection using DNA chips, artificial chromosomes, and IVF will probably change us even more, and soon.

038—…”An amazing thing is that the manipulations to do those kinds of experiments [gene repairs] are actually much simpler in germline than in somatic therapy. If I had to project, I think fifty years from now we will be doing everything through the germline rather than in somatic tissues.”

To understand why germline interventions seem easier, we must look at the fundamental challenge to all gene therapy: making a new gene active in the right place, at the right time, to the right extent. Somatic gene therapy’s success relies on placing a modified gene into the cells of some target tissue and ensuring that the gene is active only there. This is no simple matter for hard-to-reach internal organs like the liver, for dispersed tissue such as muscle, and for diseases in which therapy requires the repair of nearly all afflicted cells.

Early clinical research has focused on particularly accessible tissue such as the lining of the lung and white blood cells. With cystic fibrosis, for example, researchers can use inhalants containing viruses that can carry a gene into the mucosal cells in the lung’s lining. For patients with adenosine deaminase deficiency, an immune disease in which certain white blood cells are unable to function normally, doctors draw a patient’s blood, extract the white cells, alter them, and infuse them back into a vein. With these therapies, the cells are relatively easy to reach, so researchers concentrate on refining the viral vectors and other methods of getting a modified gene into the cells and keeping it active.

044—Unraveling the genetic differences among human populations sharing common ancestries may be difficult, but such differences also exist. Concern is so great about our ability to deal with the potential implications that investigators using data from the primary database on human genetic diversity at the NIH are required to sign a form stating they will not try to determine the ethnicity of the people who donated the samples. Although every one of the world’s top two hundred times in the hundred-meter dash is held by someone of West African ancestry, it is commonly asserted that black athletic dominance of specific sports has nothing to do with genetics. So heightened are our political sensitivities about racial matters that some say the possibility of a genetic link should not even be examined.

Sir Roger Bannister, who broke the four-minute-mile mark in 1954 and is a retired Oxford dean, was sharply criticized when, at the 1995 meeting of the British Association for the Advancement of Science, he said, “As a scientist rather than a sociologist, I am prepared to risk political incorrectness by drawing attention to the seemingly obvious but under-stressed fact that black sprinters and black athletes in general all seem to have certain natural anatomical advantages.” Theresa Marteau, of the Psychology and Genetics Research Unit at Guy’s Hospital in London, responded, “It is potentially racist to look at the biological factors. I don’t need to know whether what Bannister said is correct. And I don’t think there needs to be research.”

Avoidance is no solution. Genetics is clearly a key ingredient in athletic performance, as it is in other areas, and genetic differences among populations long isolated reproductively may cause a shift in the average potential of individuals in those populations. But generalizations about “blacks” and “whites” oversimplify and distort matters by suggesting some underlying unity within these categories. The broad groupings defined by superficial attributes like skin color include many distinct populations, each with its own common ancestry, and many people with mixed lineages. The genetic differences among ten black Africans from different parts of that continent, for instance, are far greater than the differences among ten light-skinned individuals from scattered places around the world.

Such sensitive issues will not remain in limbo much longer. Research will show that the influence of our genes on some human attributes is unclear or too hard to decipher, but other influences may be straightforward. The answers will be just another byproduct of the Human Genome Project. How we respond to this new information will be one of the biggest social and intellectual challenges of coming decades, for we will learn a great deal about ourselves that many people would rather not face. To date, most discussions of genetic information have focused on such issues as genetic privacy and whether to allow genetic testing for untreatable diseases like Huntington’s. This is just the tip of the iceberg. Wait until the price of DNA diagnostic chips drops enough so that comprehensive testing becomes routine.

With the identification of every human gene, as well as the most common variants of each — the so-called single-nucleotide polymorphisms, or SNPs — we will be able to probe our genetics as never before. The key will be the DNA chip. In 1997, the company Affymetrix released the first such device, a dense grid-like array of 50,000 short DNA sequence probes on a glass chip. By mid-2000, when the rough draft of the human genome was completed, 400,000 such probes on a single chip were available for a few thousand dollars, and by early 2002, Affymetrix was selling researchers even better chips for as little as 0 each.

Dozens of large and small companies are working on chips designed to analyze tens of thousands of genes at a time. The result will almost certainly be tests that are fast, comprehensive, cheap, and reliable enough to read DNA sequences from a smear of saliva or blood. With this coming generation of gene chips, today’s efforts to track changing levels of gene expression in tumors and other tissues will expand into broad population studies that bring new insights into our genetic makeup.

There will be technical and computational obstacles to overcome in characterizing our individual genomes cheaply and comprehensively, but emerging technologies do not need to analyze our individual genomes completely. Subtle effects can wait. Tests for the several million already identified common variants of our genes will yield enough information to keep researchers, epidemiologists, and clinicians busy while analytic techniques improve.

The burgeoning computational field of bioinformatics will be critical to this effort. No single human scientist will ever examine more than a tiny portion of our genome directly; it contains too many bases. Without computers to sift through this vast mass of data to find useful correlations between our genes and key aspects of who we are, the Human Genome Project would offer us a book we could never fathom. These computer tools are also essential to sophisticated embryo screening or germline manipulation because without the knowledge emerging from the Human Genome Project, few genetic interventions could be considered.

048—The push toward therapies for adults cannot help but contribute to the development of germline technologies, but pharmaceutical development may prove even more important. While tens of millions of dollars each year go to gene-therapy research, billions will flow into pharmacogenetics — the effort to tailor pharmaceutical interventions to people’s individual genetic constitutions.

Pharmaceutical companies estimate that they spend an average of seven years and 0 million to go from the discovery of a promising compound to an approved drug. The cost is so high because about 80 percent of this expenditure is on drug candidates that never reach market. The 1997 approval of the diabetes drug Rezulin shows what can go wrong. Although the drug initially seemed a big success, when a scattering of patients began to suffer liver damage and some died, calls to withdraw it mounted and Rizulin was doomed. The deaths do not mean that the drug didn’t help anyone. Today, a drug is worthless if it benefits some patients and causes severe reactions in others. If these two groups could be distinguished in advance, however, the story would be different.

The hope of the pharmaceutical industry is that our genes will be the key to such predictions, and that as correlations are found between people’s genetic constitutions and their medical histories and drug reactions, their drugs can be personalized. This and other medical hopes are helping fuel efforts to collect massive amounts of genomic data.

Kari Stefansson, the founder and CEO of deCODE Genetics, in Reykjavik, Iceland, has moved aggressively to uncover what the genes of Icelanders can tell us about disease. Until in-depth genetic surveys become affordable, deCODE must lean heavily on family histories, which makes Iceland an ideal place for prospecting. It has detailed medical records that go back to 1915, century-old genealogical records, and a homogeneous population descended from small bands of tenth-century Norse and Celtic settlers. In December 1998, Stefansson reached an unprecedented agreement with the Icelandic government to link the country’s health-care records with genealogical information about the island’s 275,000 inhabitants, and license the information to deCODE. Three quarters of the population supported the initiative, and many Icelanders have given blood samples to provide detailed genetic information for the studies. The pharmaceutical company Hoffmann–La Roche was impressed enough to sign an agreement specifying research milestone payments totaling up to 0 million.

Such information helps find the genes implicated in various diseases, but if DNA chip technology moves quickly, large-scale genetic surveys that ignore genealogy will largely supersede Stefansson’s approach. Researchers will depend less on finding disease genes in well-studied families and more on comparing genetic test results from tens of thousands of people who have a particular disease. Collaborative Genomics and other companies are already collecting hundreds of thousands of patient histories and tissue to prepare for such efforts. The government of Estonia is preparing to assemble genomics data for research on its 1.4 million citizens; the island nation of Tonga has signed an agreement with an Australian genomics company to compile data on its 100,000 inhabitants; and a company called Lifetree Technologies is collecting genetic samples from funeral homes and cremation societies.

053—In vitro fertilization is now the choice of tens of thousands of couples who would not otherwise be able to have children, and in some clinics, the success rate for women under thirty-five is more than 70 percent per ovulatory cycle, much higher than for natural conception. In the United States in 1998, 28,000 babies were born this way, and doctors performed 80,000 cycles. The biggest complaint is not that IVF is immoral, but that it costs so much and often doesn’t work. An IVF cycle in the United States typically costs about ,000 and is not covered by health insurance.

No matter what methods eventually arise for shaping the genetics of human embryos, IVF procedures — the extraction of eggs, their in vitro fertilization, and the implantation of the resultant embryos — will underlie these methods. So present efforts to refine and enhance IVF procedures are also working toward germline interventions.

056—Three technologies will likely combine to convert IVF into a commonplace reproductive procedure that is suitable for germline interventions. The first will be the maturation of immature eggs retrieved by simple ovarian biopsy. This will raise the number of eggs a woman might use for reproduction and eliminate the need for heavy doses of hormones to stimulate her ovaries. The second will be the freezing and thawing of immature eggs without damaging them. This will allow a young woman to bank healthy eggs without having to decide then and there whose sperm will eventually fertilize them. She could thaw eggs from this external artificial ovary anytime, then mature and fertilize them to make large numbers of embryos. The third technology is comprehensive genetic testing of embryos. Such non-damaging testing would allow couples to make meaningful choices about the embryos they implant.

Genetic testing of embryos is nothing new. Physicians first performed preimplantation genetic diagnosis (PGD) in 1989 at London’s Hammersmith Hospital by teasing a single cell from each of several eight-cell embryos and testing the gender of the cells, so they could implant a female embryo and avoid a sex-linked disorder that occurred only in males. Two years later, the same physicians tested for a genetic mutation that causes cystic fibrosis and enabled a high-risk couple to implant an embryo free of the disease. Today, couples can use PGD to screen for a handful of genetic diseases, including hemophilia, Tay-Sachs, and fragile X syndrome, which can cause severe mental retardation in males. Because of high cost, limited availability, and the small number of conditions that can be tested, the procedure is still rare, but in a decade the landscape will differ. Scientists will have identified associations between constellations of genes and various physical and mental attributes, including the risks for common diseases. Couple this with the future use of PGD to look at many more genes in a single embryo, and we will probably be able to test an embryo and obtain solid information about the child it would become. Parents will then have a choice as to which potential child they’d like to bring into being.

The usefulness of such embryo testing will depend on the extent to which our genes shape us and on the complexity of their influences. Some important aspects of who we are will turn out to be largely independent of our genes; others will have strong genetic contributions. At present, our knowledge of this is only general. Lung cancer, for example, seems to depend mostly on environmental influences, while prostate cancer appears to be more influenced by genetic predisposition. In a decade or so, however, we should have solid, specific answers about many of these relationships.

We are the result of an intricate interplay of genes and environment, and the two are interdependent. Our genetic tendencies can shape our environment by steering our choices, and environmental influences can switch genes on or off. This means that as society ever more successfully eliminates extreme variations in environment — say, by providing basic nutrition and education to all — genes will become more, not less, important influences in shaping us. As we correlate our genetic constitutions with the details of our health, personality, and behavior, we will learn not what our genes determine in some absolute sense, but what possibilities they push us toward within the normal range of environments we encounter. Deciphering the workings of our biology and the influences of experience and environment will give us more control over our lives by offering us more effective ways of diminishing the vulnerabilities and adding to the potentials that our genes bring us.

058—Germline selection and manipulation lie beyond medicine’s present boundaries, but these boundaries may shift rapidly in response to public interest as real opportunities emerge. In a 1993 international poll, Daryl Macer, the director of the Eubios Ethics Institute in Japan, found that a substantial segment of the population of every country polled said they would use genetic engineering both to prevent disease and to improve the physical and mental capacities inherited by their children. The numbers ranged from 22 percent in Israel and 43 percent in the United States to 63 percent in India and 83 percent in Thailand.

Speaking to a pollster about abstract choices is one thing; making concrete decisions about our children’s genes is another. But widespread use of coming reproductive technologies is not hard to imagine. Large numbers of young women would likely bank eggs if they could do so easily. If nothing else, that would calm the angst about their biological clocks running out. Many such women, of course, would never use their banked eggs; they would conceive their children through sex. But other women would choose embryo implantation, seeing it as a trivial procedure too good to pass up. Some couples would find the option of timing the conception and birth of their child compelling. Others would want to screen for worrisome genetic diseases or eliminate the spontaneous abortions caused by genetic abnormalities. Still others would want to select some attribute of their future baby: gender, adult height, hair color, or temperament. The motivations behind such choices would be as personal and varied as the lifestyles and values of the couples.

Women who have banked eggs would not be the only ones to avail themselves of these options. Millions of couples have infertility problems. The numbers of people who use IVF would swell when the procedure became less expensive and onerous, and they too would find such choices enticing. Also, as IVF became easier, many women who never bothered to freeze eggs might decide to use the technology simply for the choices it offered them.

The procedure would be straightforward. Typically, a woman would enter an IVF clinic as she does today, but instead of facing an exhaustive ordeal, she would have an ovarian biopsy to obtain fresh eggs or would just send for her previously frozen eggs. Her partner would deposit sperm as he does today or send for previously frozen sperm. In light of the recently identified risks in conceptions by men over forty, such sperm banking could well become increasingly common. Conception would occur in the laboratory, and the woman would later return to have the growing embryo implanted.

For “natural” conception, the woman would implant one of the embryos at random. For disease screening, she would implant one that had passed a genetic test for chromosomal abnormalities and disease mutations. For embryo selection, she would implant the one whose PGD results best matched the genetic predispositions she and her partner had chosen. For germline intervention, she would also implant a selected embryo, but one whose genes had been modified.

065—Widespread modifications of human genetics will require reliable generalized methods for germline intervention. The human artificial chromosome, pioneered by John Harrington and Huntington Willard in 1997 at Case Western Reserve University, has that potential. This technological descendant of the bacterial artificial chromosome and the yeast artificial chromosome, which have been in use for many years, contains all the essential elements for chromosome functioning. In 2001, two companies were at the vanguard in developing this technology.

Back in 1998, one reported that its synthetic chromosomes had passed stably through more than a hundred cell generations in human tissue culture. And in 1999, the other announced that its artificial chromosomes had been retained by successive generations of mice reproducing normally. The implications of the mouse result for human germline interventions were so clear that the inventors felt compelled to state that they planned to use the technology only for animal transgenic work and human somatic therapy, and would not license the chromosomes for human germline therapy. It is doubtful that this will have any more long-term impact on the use of the technology than statements from the Roslin Institute opposing human cloning.

Adding a new chromosome pair (numbers 47 and 48) to our genome would open up new possibilities for human genetic manipulation. The advantages of putting a new genetic module on a well-characterized artificial chromosome instead of trying to modify the genes on one of our present 46 chromosomes are immense. Not only could geneticists add much larger amounts of genetic material, which would mean far better gene regulation, they could more easily test to ensure that the genes were placed properly and functioning correctly.

Because an artificial chromosome provides a reproducible platform for adding genetic material to cells, it promises to transform gene therapy from the hit-and-miss methods of today into the predictable, reliable procedure that human germline manipulation will demand.

Ideally, an unloaded auxiliary human chromosome would have no functional genes of its own. It would be an inert scaffolding dotted with independent insertion sites where modules of genes and their control sequences could be placed using the various enzymes that splice and clip DNA. With adequately separated sites, the eventual payloads of genetic modules would not interact with one another and could be expressed independently. The auxiliary chromosome would be a universal delivery vehicle for gene modules fashioned by medical geneticists throughout the world. At first, only a few safe and effective modules would exist, primarily those specific constellations of gene variants known to confer clear advantages because they occur naturally and have obvious benefits. Eventually, geneticists might develop hundreds of such modules, each with its own particular benefits and risks.

Delivering gene modules using synthetic chromosomes would be the safest and least intrusive way to substantially modify our genetics. By not altering a single one of the 3 billion bases on our existing chromosomes, geneticists would minimize the chance of inadvertently stepping on the many yet unappreciated interactions within our genome. Given the limits of our knowledge, however, we would be wise to design any insertion sites to include a mechanism for selectively switching off the expression (that is, the activity) of the genetic module placed there. An injection could provide the chemical signal that would trigger the shutoff.

073—To understand how such targeting would work, we first need to look a little more closely at how genes are regulated. The promoter, a stretch of DNA immediately upstream from a gene’s coding region, is one of the best understood of a gene’s regulatory elements. Promoters serve as attachment sites for special protein factors that enable a promoter’s associated gene to be expressed. Our genome codes for thousands of such factors, and the particular ones a cell makes determine which genes and groups of genes are active in that cell.

088—A successful germline intervention that significantly extended mouse longevity would ignite a huge effort not toward germline interventions in human embryos, but toward clinical interventions in adults. As Aubrey de Grey, the tall, full-bearded, rather eccentric British theorist on aging, who organized the roundtable on reversing age-related decline, said to me, “Germline manipulations on future generations don’t interest me. I already have aging.” So do we all. Researchers are using germline techniques as a tool for understanding aging and figuring out how to combat it directly in adults, not as a prelude to human germline manipulation, though this may prove easier.

Any drug that retards key aspects of aging would have sales that dwarf today’s disease-specific blockbusters. Virtually every adult might take anti-aging medications for life — and a dollar a day from everyone older than forty-five is billion a year in the United States alone. Given such incentives, biomedical science is likely to come up with adult therapies for at least some facets of aging, but ultimately, germline technology may prove a more potent tool for so intrinsic a part of our biology.

095—Whatever our attitudes about biological enhancement, I suspect that most of us would rather be among the first to live an extended lifespan than among the last to live a “natural” one. Yet the idea of striving to extend our lives is somehow discomforting. We celebrate the nobility of self-sacrifice and the heroism of risking death for the common good. We do not applaud those reaching for longevity. Their self-serving actions evoke images of cowards on the deck of the Titanic, pushing aside women and children to clamber into lifeboats, or hypochondriacs counting their every vitamin and avoiding anyone with a cough, or, yes, even vampires sucking the blood of others to buy immortality. It is easy to recoil from those who practice caloric restriction and starve themselves in the pursuit of added years. The travails of their quest are reminiscent of religious ascetics, but their goal seems unworthy and narcissistic.

We should look more closely at the source of our repugnance, however. Today those grasping for longer life seem to be relinquishing life’s richness and focusing solely on themselves and their survival. Small wonder at the disdain they sometimes provoke. But real breakthroughs in the biology of aging would change this. We might not be willing to starve ourselves to buy a few years, but surely we would take a pill. This would be neither selfish nor self-absorbed; it would be common sense.

100—Researchers have run hundreds of studies in numerous countries and examined various traits in various types of twins. The results have been remarkably consistent. Genetic factors generally account for between 35 and 75 percent of the variation among people in traits we think of as significant. Environmental influences and random factors that are unique to each individual account for most of the rest, whereas environmental influences shared by an entire family matter little, at least within the range of environments encountered by a typical child growing up in the developed world.

I have been speaking of genes and environment as though they are independent, but this is not the case. Genes not only affect our minds and bodies directly by shaping our biology, they also do so indirectly, by influencing the environment we experience. A child who excels at sports is more likely to gravitate toward athletic activities, just as one who loves to read philosophy might choose more intellectual pursuits. Both children would be selecting their environments. This happens in less overt ways as well. A reclusive, rigid child almost certainly elicits different treatment from those around him or her than one who is gregarious and easygoing. Thus, self-reinforcing feedback comes into play: our biological predispositions shape our environment, which in turn reinforces our predispositions. Some of the spread that exists in estimates of the heritability of IQ, for instance, may arise because of the dissimilar ages of the subjects in different studies. By late adolescence, twins tend to be closer in IQ than they were in childhood, which may be because of their growing power to align their activities with their underlying predispositions. Similar results show up with qualities such as antisocial behavior.

IQ provides a good example of the difficulties we face in teasing apart the relative contributions of environmental and genetic factors. Many studies have looked at the heritability of intelligence, and although some of them have been challenged as flawed or even fraudulent, the work typically shows that IQ is anywhere from 45 to 75 percent heritable. Moreover, some studies conclude that adopted children living together show no more correlation in their IQs than other unrelated individuals. The households covered in these studies do not include extremes of poverty and environmental disadvantage, but absent this, the influence of living in one home rather than another is small.

Not surprisingly, studies of the biology of intelligence are highly controversial. While almost no one claims that IQ accurately gauges all the dimensions of human talent, people who score higher on these tests clearly tend to apprehend, scan, retrieve, and respond to stimuli more quickly than those with lower scores. Moreover, IQ is one of the most useful predictors of school performance, years of education, job performance, and income. Such correlations are statistical, of course, and cannot tell us what will happen to a particular individual. Some geniuses are too dysfunctional even to hold down a job. But these correlations with IQ are real, they are significant, and they may grow stronger as our society becomes more complex and technology intensive. Deciphering, reading, and manipulating the genes involved in human intelligence are going to be thorny political issues, to say the least.

Long before the genomics revolution, stories of uncanny similarities between identical twins were contributing to the idea that our genes determine much about our personalities. The most publicized such twins were probably the so-called Jim twins, James Springer and James Lewis, whose story broke in 1979 in the Minneapolis Tribune and inspired Thomas Bouchard to launch his famous twin study.

110—I refer to this whole realm, which extends all the way from rudimentary embryo diagnostics to germline enhancement, as germinal choice technology, or GCT. “Germinal” emphasizes that GCT manipulates one or a very few of our germinal cells rather than a fetus and is directed toward creating (or germinating) life rather than terminating it. “Choice” acknowledges that our personal preferences will help determine our children’s genes. “Technology” recognizes the entry of laboratory machinery into human reproduction to externalize the process of conception.

Choosing Genes

Some parents insist that their children study hard and earn good grades. Some push their kids toward sports. Some want outgoing and popular offspring. Whether we guide our children with a heavy hand or are subtle and indirect, the paths we try to choose for them often tell more about us than about them or who they will become.

126—Some nations may hold off the technology for a while, but the longterm impact of such bans will be no greater than previous such efforts. Germany, haunted by its Nazi past, opposed genetic technology for many years and in 1991 enacted an Embryo Protection Law that was the most restrictive in the world. By 1993, however, the realization had sunk in that biotechnology would pass the country by, and Germany moderated its tight restrictions on great swaths of genetic research. In 2000, the nation went further and began to debate the watering down of the 1991 law. Switzerland, home to many pharmaceutical companies, seemed especially unlikely to lead a charge against genetic medicine, but in 1997 it almost did. The Swiss nearly passed a plebiscite to ban such research. They blinked only when the economic costs of driving drug companies abroad became clear, and in 2000, another plebiscite there, this time to ban IVF, lost by a margin of more than 30 percent.

These economic forces operate throughout the developed world. That we will halt the global scientific effort to elucidate human genetics is inconceivable. And we will have no trouble figuring out how to justify using more potent germinal choice technologies as they emerge. Bans in this or that country surely won’t keep them from spreading. When large numbers of people want something that regulators cannot monitor and that small laboratories in any country can provide, people obtain it.

Though the prospect of genetic manipulation disturbs William Gardner, a bioethicist at the University of Pittsburgh, he argues convincingly that no ban can stop it: “Both nations and parents have strong incentives to defect from a ban on human genetic enhancement, because enhancements would help them in competitions with other parents and nations. The ban on enhancement, moreover, is vulnerable to even small defections because the disadvantages of defecting late will increase the incentives for non-defectors to follow suit, causing defections to cascade.”

Couple Gardner’s argument with the global diversity of attitudes about germline selection and enhancement, and the writing is on the wall. The inevitability of these technologies, however, doesn’t mean that no one will try to block them or that no reasons exist for concern about their possible risks. Although many people believe that the potential benefits of these technologies outweigh their dangers, many do not share this belief. Some assert that we don’t have the wisdom to shape our children in this way, others feel that we are wrong to play God. Some fear that the technology might lead to genetic discrimination, be abused by tyrants, or enable the wealthy to give their children superior talent and leave the rest of us behind. Still others worry that it might corrupt the relationship between parent and child, transform children into mere objects, or burden them with unrealizable parental expectations. In short, many people are uncomfortable with the idea that we might take control of our own evolution, and many of them would like to stop this technology.

130—Most of us would shake our heads in disbelief at anyone who argued that a child had an inherent right to an unaltered biological constitution and should undergo no surgical procedures before adulthood. When we hear the same argument against genetic manipulation, however, we take it seriously, though it is just as out of line with our values. After all, when fetal testing reveals cystic fibrosis, some 90 percent of couples in the United States choose to abort, and even more would probably avoid implanting a seriously afflicted embryo.

The most difficult type of germinal choice technology for people to accept is germline enhancement — the direct manipulation of an embryo’s genome to improve it in some way. Although as embryo screening becomes more sophisticated it will be able to match many of the immediate possibilities of direct enhancement, more complicated enhancements no doubt will require direct interventions, so in this discussion I will focus mainly on these when speaking about germline enhancement. As the ultimate example of GCT, it will no doubt figure in any serious reworking of human biology, and except for cloning, it has been the most criticized future reproductive technology.

Arguments against human germline enhancement rest largely on assertions that it is morally wrong, that it is too dangerous, that it will be badly abused, or that it could bring dire indirect consequences in personal, political, social, environmental, or spiritual ways. Let’s look at each of these.

The most common form of the first assertion, that germline enhancement is morally wrong, is: we should not play God. But there are many secular variations. Along with our “right to unaltered genes” are the ideas that children should not be manufactured, that our gene pool is the common property of all humanity, and that genetic manipulation would assault human dignity.

As for playing God, by the measure of earlier ages, we do just that every time we give our children penicillin, use birth control, fly in an airplane, or telephone a friend. We embrace technologies that tame and harness nature because we think they improve our lives, and we will accept or reject human genetic manipulation on the same grounds.

But perhaps the scale of primitive humans is no longer appropriate, and playing God is a rather hyperbolic way of speaking about any of our tinkering with the natural world. At a 2001 conference on cloning, Rabbi Moses Tendler, a professor of Jewish medical ethics at Yeshiva University, spoke against reproductive cloning, but not because he considered it playing God:

“God gave us molecules. God gave us atoms. We put them together differently. We are not playing God by doing that. We can’t get along without Him . . . God is the source of all science and God is the source of religion, and God is not schizophrenic. He doesn’t fight with Himself. If there is seemingly conflict between the two, it’s based upon one of three possibilities. We don’t understand what God said, we don’t understand the science, or, the usual explanation, we don’t understand either.”

Metaphors about “human manufacturing” are another way of articulating that germline manipulation would somehow violate the natural order. The infusion of conscious human choice into the process of conceiving a child blurs the line between the biological and the technological in the same way that artificial intelligence does, but genetic engineering is not about to turn our children into manufactured products. A freely chosen nine-month pregnancy is nothing like the controlled and optimized assembly-line manufacturing evoked by this metaphor. Moreover, children, whatever their genetic makeup, are far too influenced by the vagaries of individual experience to be anything but unique and highly individual.

Communal ownership of the human gene pool is an even stranger concept. The gene pool is a conceptual abstraction that is simply the sum total of all the genes of the reproducing population. We affect the gene pool every time we save a diabetic who would otherwise die before reproducing, every time we bring a child into the world, every time we inoculate a child, protecting him or her from fatal infectious diseases. Do those who argue for collective control of our gene pool imagine that humanity as a whole should oversee these choices as well? Such invocations of the sanctity of our gene pool are not scientific but religious arguments. John Fletcher, who was the first chief of the bioethics program at the National Institutes of Health and is now professor emeritus of biomedical ethics at the University of Virginia, commented in 1998:

“The idea of natural law is one that I think is not a viable concept when it comes to the gene pool . . . Suppose we really knew how to treat cystic fibrosis or some other very burdensome disease and didn’t do it because of the belief that people had a right to an untampered genetic patrimony. Then, you met a person twenty-five years later and did the Golden Rule thing and said, ‘Well, you know, we could have treated you for this, but we wanted to respect your right to your untampered genetic patrimony. Sorry.’ It doesn’t take a high-falutin ethicist to realize that’s just plain wrong. You violate one of the basic principles of morality, namely that you want to treat a person as you would want to be treated.”

The moral and religious arguments against genetic manipulation are unconvincing to me, but they have significant sway. Beliefs about right and wrong are deep-seated, and I would be astonished if the coming extension of human control into the intimate realm in which life passes from one generation to the next did not provoke strong reactions.

James Watson was instrumental in bringing the Human Genome Project into being. When I asked for his reaction to the idea of the “sanctity” of our genome, he couldn’t have been more blunt. “I just can’t indicate how silly I think it is,” he said. “I mean, sure, we have great respect for the human species. We like each other. We’d like to be better, and we take great pleasure in great achievements by other people. But evolution can be just damn cruel, and to say that we’ve got a perfect genome and there’s some sanctity to it . . . I’d just like to know where that idea comes from. It’s utter silliness.”

156—Almost no one, however, is pushing for these technologies; they are too threatening. I once spoke about these issues with a group of libertarians, who rail about taxes and wholeheartedly embrace global free markets. Even they voiced concerns about unregulated manipulation of human embryos. Clearly, human biological enhancement puts philosophies of individual autonomy and laissez-faire ideology to the test.

Read more about contemporary eugenics and conscious evolution at Matt Nuenke’s NeoEugenics website.

General Scientific Issues
(genes, mapping, genetic manipulation, genetic engineering)

Anderson, W. French, “Gene Therapy.” Scientific American (September 1995), 124-128.

Bowman, James E. and Robert F. Murray Jr., Genetic Variation and Disorders in Peoples of African Origin (Johns Hopkins University Press, 1998).

Davis, J., Mapping the Code: The Human Genome Project and the Choices of Modern Science (New York: John Wiley, 1990).

Gosden, Roger, Designing Babies: The Brave New World of Reproductive Technology (W.H. Freeman and Co., New York, 1999).

Hai, Yan, Kenneth W. Kinzler, Bert Vogelstein. “Genetic Testing– Present and Future”. Science 289: 1890-1892 (2000)

Holtzman, N.A. and M.S. Watson, eds., Promoting Safe and Effective Genetic Testing in the United States. Final Report of the Task Force on Genetic Testing. (Baltimore: Johns Hopkins University Press, 1998).

McFadden, Johnjoe, “Our Genes are doomed,” The Guardian, February 5, 2001. Available at: http://www.guardian.co.uk/Archive/Article/0,4273,4130720,00.html

Plomin, Robert, Michael J. Owen, and Peter McGuffin. “The Genetic Basis of Complex Behaviors.”, Science 264: 1736 (1994).

Time Magazine Special Issue, “The Future of Medicine”, January 11, 1999, Vol. 153, No. 1 (cgi.pathfinder.com/time/magazine/toc/0,3392,1101990111,00.html)

Zallen, Doris T., “Chapter 2: Basics of Genetics and Genetic Testing” in Does It Run in the Family? A Consumer’s Guide to DNA Testing for Genetic Disorders (New Brunswick, NJ: Rutgers University Press, 1997).

Cold Spring Harbor (NY) on-line DNA Learning Center at http://vector.cshl.org/

Ethical, Social and Religious Issues

American Society of Human Genetics/American College of Medical Genetics Report, “Points to Consider: Ethical, Legal, and Psychological Implications of Genetic Testing in Children and Adolescents”, American Journal of Human Genetics 57: 1233-1241 (1995).

Appleyard, Bryan. Brave New Worlds: Staying Human in the Genetic Future (Viking Press, 1998.)

Billings, Paul R., Jonathan Beckwith, and Joseph Alper, “The Genetic Analysis of Human Behavior: A New Era?, Social Science and Medicine 35: 227-238 (1992).

Buchanan, Allen, Norman Daniels, Dan Brock, and Daniel Wikler. From Chance to Choice: Genetics and Justice (Cambridge University Press, 2002).

Cranor, Carl F., ed., Are Genes Us? The Social Consequences of the New Genetics (New Brunswick, NJ: Rutgers University Press, 1994).

Deenen, Sally, “Designer People: Are We Changing the Nature of Nature?” E-Magazine, Jan-Feb 2001. Available at: http://www.emagazine.com/january-february_2001/0101feat1.html

Gardner, William, “Can Human Genetic Enhancement be Prohibited?”, Journal of Medicine and Philosophy 20: 65-84 (1995).

Glover, Jonathan. What Sort of People Should There Be? (New York: Penguin Books, 1992).

Hubbard, Ruth and Elijah Wald. Exploding the Gene Myth (Boston: Beacon Press, 1997).

Juengst, Eric T. and LeRoy Walters. “Gene Therapy: II. Ethical and Social Issues,” in Warren T. Reich, ed., Encyclopedia of Bioethics (revised ed.; 5 vols.; New York: Simon & Schuster Macmillan, 1995), II, 914-922.

Kevles, Daniel J. and Leroy Hood, eds., The Code of Codes: Scientific and Social Issues in the Human Genome Project. (Cambridge, MA: Harvard University Press, 1992).

Kimbrell, Andrew, The Human Body Shop: The Cloning, Engineering, and Marketing of Life (Regnery Publishing, Inc, 1998).

Kohlenberg, Leah. “Designer Babies?” Salon. Oct. 5, 2000. http://archive.salon.com/health/feature/2000/10/05/bone_marrow/index.html

Lantos, John, “Ethical Issues in Growth Hormone Therapy”, Journal of the American Medical Association 261: 1020-1024 (1989).

Lomax, Elizabeth M.R., Jerome Kagan, and Barbara G. Rosenkrantz, Science and Patterns of Child Care (San Francisco: W.H. Freeman, 1978)

McGee, Glenn, The Perfect Baby (Lanham, MD: Rowman and Littlefield Publishers, 1997).

Murray, Thomas H., The Worth of a Child (Berkeley: University of California Press, 1996)

Murray, Thomas H., Mark A. Rothstein, and Robert F. Murray Jr., eds., The Human Genome Project and the Future of Health Care (Medical Ethics Series). (Indiana University Press, 1996).

Nelson, J. Robert. On the New Frontiers of Genetics and Religion (Grand Rapids, MI: William B. Eerdmans Publishing Company, 1994).

Parens, Erik, ed., Enhancing Human Traits: Ethical and Social Implications (Washington, D.C.: Georgetown University Press, 1998)

Parens, Erik, “Is Better Always Good? The Enhancement Project” (A Special Supplement to the Hastings Center Report, 28: S1-S18, January-February 1998)

Rifkin, Jeremy. The Biotech Century: Harnessing the Gene and Remaking the World (J.P. Archer: May 1998).

Sears, R.R., “Your Ancients Revisited: A History of Child Development”, in E. M. Hetherington, ed., Review of Child Development Research, volume 5 (Chicago: University of Chicago Press, 1975)

Singer, Peter and Deane Wells, “Genetic Engineering”, in Erwin Edward, Sideny Gendin, and Lowell Kleiman, eds., Ethical Issues in Scientific Research: An Anthology (New York: Garland Publishing Co, 1994).

Stock, Gregory. Redesigning Humans: Our Inevitable Genetic Future ( Houghton Mifflin Company, 2002).

Walters, LeRoy and Julie Gage Palmer, The Ethics of Human Gene Therapy (New York: Oxford University Press, 1997).

Weiss, Michael J. Improving Nature? The Science and Ethics of Genetic Engineering (Cambridge Univ Press, 1996).

Wivel, Nelson A. and LeRoy Walters. “Germ-Line Gene Modification and Disease Prevention: Some Medical and Ethical Perspectives.” Science 262: 533-538 (1993).

History: The Nature/Nurture Debate and the Eugenics Movement

Baumrind, D. “The average expectable environment is not good enough.” Child Development, 1993, 64, 1299-1317.

Duster, Troy, Backdoor to Eugenics (New York: Routledge, 1990).

Gallagher, Winifred. Just the Way You Are: How Heredity and Experience Create the Individual (Random House, 1997)

Lewontin, R.C., Stephen Rose, and Leon J. Kamin, Not in Our Genes: Biology, Ideology, and Human Nature (New York: Pantheon, 1984).

Paul, Diane B. Controlling Human Heredity: 1865 to the Present (Atlantic Highlands, NJ: Prometheus Books, 1995).

Paul, Diane. The Politics of Heredity : Essays on Eugenics, Biomedicine, and the Nature-Nurture Debate (SUNY Series, Philosophy and Biology) (State Univ of New York Press, 1998)

Rothman, Barbara Katz. Genetic Maps and Human Imaginations: The Limits of Science in Understanding Who We Are (New York/London: W.W. Norton & Co., 1998).

Rutter, M. et al.. “Integrating nature and nurture: Implications of person-environment correlations and interactions for developmental psychopathology.”

Development and Psychopathology, 1997, 9 (2), 225-364.

Skodak, M. & Skeels, H. “A final follow-up study of 100 adopted children.” Journal of Genetic Psychology, 1949, 75, 85-125.

Steen, R. Grant. DNA and Destiny : Nature and Nurture in Human Behavior (Plenum Press, 1996).

Sternberg, Robert J., and Elena Grigorenko. Intelligence, Heredity, and Environment (Cambridge University Press, 1997).

Thomas, A. & Chess, S. Temperament and Development. New York: Brunner/Mazel, 1977

Public Policy Issues

Ad Hoc Committee on Genetic Testing/Insurance Issues, “Background Statement: Genetic Testing and Insurance.” American Journal of Human Genetics 56: 327-331 (1995).

Aldhous, P. “Who Needs a Genome Ethics Treaty?” Nature 351: 507 (1991).

Andrews, Lori B., Jane E. Fullarton, Neil A. Holtzman, and Arno G. Motulsky, eds. Assessing Genetic Risks: Implications for Health and Social Policy (Washington, D.C.: National Academy Press, 1994).

Annas, George J. and Sherman Elias, eds., Gene Mapping: Using Law and Ethics as Guides (New York: Oxford University Press, 1992).

Buchanan, Allen, Norman Daniels, Dan Brock, and Daniel Wikler. From Chance to Choice: Genetics and Justice (Cambridge University Press, 2002).

Cohen, Sherrill and Nadine Taub, eds. Reproductive Laws for the 1990s (Clifton, NJ: Human Press, 1989).

Gardner, William, “Can Human Genetic Enhancement Be Prohibited? Journal of Medicine and Philosophy 20: 65-84 (1995)

Nowlan, William. “A Rational View of Insurance and Genetic Discrimination”. Science 297: 195-106 (2002). http://www.sciencemag.org/cgi/content/full/297/5579/195

Silvers, Anita, David Wasserman, and Mary Briody Mahowald. Disability, Difference, Discrimination : Perspectives on Justice in Bioethics and Public Policy (Point/ Counterpoint) (Rowman & Littlefield, 1998).

Stock, Gregory. Redesigning Humans: Our Inevitable Genetic Future ( Houghton Mifflin Company, 2002).

Walters, LeRoy. “Human Gene Therapy: Ethics and Public Policy,” Human Gene Therapy 2: 115-122.(1991).

Weiss, R. “Predisposition and Prejudice: As Scientists Crack the Code of Inherited Imbalances, Policy Makers Confront the Specter of Genetic Discrimination”, Science News 135: 40-42 (1989)

The Policy News and Information Service website at url:

http://www.policy.com/issuewk/1998/1130_45/detail150.html

Genetic Explorations in Science Fiction, Theatre, and Films

Aldiss, Brian W., Trillion Year Spree (Avon, 1988)

Bear, Greg, Blood Music (Paperback reprinted: Ace Books, 1996)

Cherryh, C.J., Cyteen (Warner Books, 1995)

Dick, Philip K. Do Androids Dream of Electric Sheep? (Del Rey, 1996)

“Gattaca – There is no Gene for the Human Spirit” (Movie from 1997)

Huxley, Aldous, Brave New World (Harper Perennial Library, 1998)

Shelley, Mary W., Frankenstein: Or, the Modern Prometheus (W.W. Norton & Company, 1996)

Sterling, Bruce, Holy Fire (Bantam Spectra, 1996)

Wells, H.G., The Island of Dr. Moreau (Bantam Books, 1994)

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