Up to the Edge of Creation
Who should be born and who should not? What should be private genetic information and what should be held in public trust? Will we be able to choreograph our own evolution? Moreover, should we? Atlantans join the search for answers.
Atlanta Magazine | November 1996
How much do you want to know about the rest of your life? Suppose that tomorrow you were issued a sheet of paper or, say, a computer disk that contained your complete genetic code.
It might reveal, for instance, that you carry a mutation on the X chromosome indicating a 50 percent chance that your first son will be born mentally retarded. Or you might learn that 10 years from now, about the time you are ready to buy a second home, you will likely experience the mental deterioration and ultimate dementia of Huntington’s disease.
On the other hand, genetic tests might reassure you that even though your sister had a child with Down’s syndrome, the likelihood is the baby in your womb is going to be fine. Your genetic summation could state definitively that you did not inherit the gene that gave your mother breast cancer or that you do indeed carry genes “associated” with high IQ, irrepressible happiness or boundless creativity. All deduced from a simple blood sample, hair fiber or dab of saliva. Biologically speaking, the extraction and sequencing of your individual genotype would constitute the greater part of your life’s script.
Your so-called Genetic Report Card.
Almost weekly we hear reports of new genes discovered that account for the panoply of human variation, from disease to temperament. Over the next decade there will inevitably be hundreds of genetic tests flooding the market, confronting us with the secrets of our chemical selves. And just as the present day demands a proficiency in computers, tomorrow will require a new standard of genetic literacy to make sense of a revolution that is already raising mind-bending questions about our individual and collective futures.
Who should be born and who, perhaps, should not? What should be private genetic information and what should be held in the public trust? If genes are shown to be responsible for alcoholism, sexual orientation or violence, what does that suggest about our present concepts of self-determination and responsibility? In the furious race to cash in on the promises of medical genetics, are researchers guided by a moral compass? And, ultimately, if genetics is as powerful as the constant barrage of media reports would suggest, may we even someday be able to choreograph our own evolution? Moreover, should we?
The catalyst for such questions is the Human Genome Project, a government-funded international collaboration of hundreds of private labs—including ones at Atlanta’s Emory University—that are working to identify the estimated 100,000 genes strung along our 23 pairs of chromosomes. The project, initiated in 1990 by the Department of Energy and the National Institutes of Health, will cost an estimated 3 billion taxpayer dollars over 15 years. Variously dubbed The Code of Codes, The Book of Man and The Human Blueprint, it has been heralded as “big science” on the scale of Apollo or the Manhattan Project as well as criticized as bad science, nonscience and junk science.
In any case, scientists are identifying at least a gene a day, and hardly a week passes when they don’t claim to have found a function for one, including genes related to AIDS immunity, Huntington’s disease, cystic fibrosis, Down’s syndrome and a variety of cancers, as well as the genetic components for such phenomena as multiple nipples and chronic bed-wetting.
For physicians, molecular genetics will culminate in techniques by which they may soon diagnose the most crushing diseases with a simple cheek swab, then locate the offending or missing gene and replace it with little more bother than a mechanic takes to change spark plugs. Recombinant DNA—the practice of splicing genes from one organism to another—promises a new generation of drugs that will be more effective and perhaps cheaper than their predecessors.
Genetic engineering has given us plants that produce their own insecticides, tobacco laced with firefly DNA (it actually glowed), sheep spliced to goats (the “geep”), salmon crossed with cows, and mice, sheep and pigs bred with human DNA. Genetics currently has applications in everything from controlling pests to restoring blighted forests, from tracking criminals to tracking ancient human migrations.
Dr. Douglas Wallace, chairman of Emory University’s esteemed department of genetics and molecular medicine, believes that in the not-too-distant future geneticists may even be able to intervene in the aging process. “This won’t happen today or next week,” says Wallace, “but it is happening now, and in the next 25 to 50 years something fundamentally different will have occurred to humans.”
Exactly what that something is, however, nobody seems to know.
The New Pariahs
A small classroom at the extreme south end of Wheeler High School is hung with banners of encouragement. The teacher’s desk is strewn with childlike artwork and the scribbles of her best students, many of whom arrive each morning on a little yellow bus, often speaking to no one on their way to a place the other kids sometimes refer to as “the retarded class.”
In more than 20 years Ellen Levine has taught every range of special education student. Some have seemed “normal” in every way, but perhaps can’t count change or remember their phone numbers. There have been lives limited by voice synthesizers, keyboards and the awkward rigging of motorized wheel chairs. Lives cursed with flaying limbs or uncontrollable urges to mutilate their own bodies. Lives for which early death may seem only a deliverance. Lives that modern genetics offers to prevent.
“The assumption that these kids ought not come into the world troubles me,” says Levine, as she is cleaning out her desk on the first day of summer vacation. “I mean, where is our problem? Is it with people with disabilities or is it with society’s acceptance of people with disabilities? Are we trying to fix things that aren’t necessarily broken?”
The science of improving the hereditary qualities of a race or breed is called eugenics, and some fear that new insights into how to control the transmission of our genes will lead to a resurgence in official eugenic policies, which in this country once included compulsory sterilization of inmates and the “feebleminded.” Eugenics has enjoyed a long history in Western thought, from George Bernard Shaw to Oliver Wendell Holmes, but reached its most heinous manifestation in the social policies of Nazi Germany.
“Genetic engineering is a very complicated process. This isn’t something that you can do in your garage with a couple of friends,”
Actually, modern genetics shows that although we might prevent the birth of those with a genetic disease, we cannot eliminate the occurrence of the gene itself within the species. Most inherited conditions are recessive, are never manifest as disease in carriers, and the gene mutations are so widespread in the population (1 in 22 Caucasians carry the common mutation for cystic fibrosis, for example) as to be virtually uninfluenced by direct manipulation of the genes themselves.
“The idea that by prenatal diagnosis we are going to change the overall genotype of the society is simply wrong,” says Wallace. “[Homo sapiens] is going to be the same species. It is going to have the same diseases and the same frequencies of mutation. The difference is only whether we are going to deal with the negative repercussions of our genotype.”
But it is exactly words such as negative that confuse the distinction between genetics and eugenics, since the fundamental tenet of eugenics is that it is better to bring certain types of people info the world than others. This notion of better or worse traits also dogs the concepts of genetic screening and testing, terms that by definition suggest the need to guard against something inherently bad.
“There are some diseases that, sure, we want to prevent, and that is the good thing about genetic testing,” says special ed teacher Ellen Levine, who underwent prenatal screening for Tay-Sachs disease. As an Ashkenazi Jew, she is at elevated risk for passing along the Tay-Sachs gene. “But that is a devastating disease,” she says, “and those [Tay-Sachs] children are not going to live, which makes it even worse, because the child starts out normal.”
But as one Emory researcher points out, some parents may consider a life cut mercifully short by Tay-Sachs disease actually less cruel than a life plagued by the pain, embarrassment and frustration of seemingly less severe conditions such as crossed eyes, a clubfoot or cleft palate. Thus, if suffering and the perceived severity of a disease is the deciding factor in who should be born and who should not, where do we draw the line? And who decides?
To Doug Wallace, whose own son was born with an undiagnosed neuromuscular disorder, what matters is simply the right to have genetic information. “I believe very strongly that it needs to be up to the parents how they want to handle their own reproductive potential, based on whatever information they want—which could be none. Nobody is under any obligation. Genetic information is a gift. It is not something that is crammed down anybody’s throat.”
But in many cases there is still a gap between having genetic information and knowing how to use it. Relatively few human traits correlate on a one-to-one basis with the presence of a single gene. Diseases may be influenced by “background” genes, environmental factors, health of the mother during pregnancy, lifestyle and diet. Many of the same genes are “turned off” or “turned on” quite differently in different people. Some tests will inevitably be imperfect, leading to decisions that are based on erroneous information, and the vast majority of genetic tests will be available without any accompanying cure.
Even if we eventually can predict the exact occurrence and severity of diseases, what of those people who have overcome such disabilities? Would society be better off without the eminent theoretical physicist Stephen Hawking, who suffers from Lou Gehrig’s disease? Or without Lou Gehrig? Woody Guthrie, who wrote hundreds of folk songs, died of Huntington’s disease. The neuropsychologist Nancy Wexler, who had a parent die of Huntington’s disease, helped discover the gene that causes it.
Beyond genetic testing, there is also the possibility that we will someday be able to alter or eliminate the transmission of a given gene in a family line. In so-called germ-line therapy, the DNA of a person’s sperm or egg cells—or perhaps even that of a nascent embryo—is altered. Though entirely feasible, most researchers and ethicists agree that germ-line therapy is currently out-of-bounds because the technique is imprecise, fraught with the possibility of negatively affecting a family’s lineage.
“We are a long way from that [germ-line therapy]. But I think somebody might at least make an argument for it,” says Dr. Paul Fernhoff, medical director of the Emory Genetics Laboratory. “I don’t think any of us would say, ‘I prefer [inheriting] a gene that causes cancer.’”
Yet at what point will we have left off curing disease and begun creating people?
The private fertility industry, where many of the emergent genetic technologies are bound to be employed, treats as many as 1 million patients a year, with profits estimated in the billions. There is virtually no regulation of the field. So what’s to prevent America’s obsession with beauty, intellect or athleticism from infiltrating new reproductive technologies?
“That’s why we have ELSI,” says Femhoff, who points out that from the inception of the Human Genome Project, DOE and NIH have devoted three to five percent of their budgets to study the project’s Ethical, Legal and Social Implications. Though ELSI watchdogs have no authority over how genome information will be applied in the private sector, genetic experimentation is still subject to scrutiny from research colleagues, grant review panels, academic review boards and the National Institutes of Health. The American Medical Association recently adopted guidelines rejecting genetic techniques that would seek to enhance or optimize human characteristics.
“Genetic engineering is a very complicated process. This isn’t something that you can do in your garage with a couple of friends,” says Emory researcher Steve Warren, who headed Emory’s early involvement in the genome project. Furthermore, short of germ-line intervention, we still only have the ability to test for disorders rather than make improvements.
Nonetheless, human geneticists and their critics agree that if we transpose the coming technologies over existing prejudices and fears, the result could be a kind of eugenics in which couples prevent the birth of those with whom society is least comfortable, opting against children with genetic markers for intellectual or physical disability, obesity, homosexuality or overaggressiveness.
The huge amounts being spent on research and development of new biotechnologies may also make initial applications unaffordable for many. Thus low-income segments of the population could easily be buried under the weight of “lower-class diseases,” further dividing society into a genetically privileged culture and the culture of deformity, dementia and distress. In short, genetic pariahs.
Even Doug Wallace sees this as a possibility, if not an eventuality. “The technology is going to develop. The question is whether people will be given equal access to it,” he says. “I see quite the contrary.”
The Golden Grail of Medicine
Gail Heyman says hers is just a normal family. She and her husband, Lyons, have a house in the suburbs, a place on Lake Lanier, three children, a dog and a mutation.
The mutation, called fragile X, can lay unexpressed in a family line for generations. In its eventual manifestation, female carriers pass along a gene that leaves the X chromosome looking as if one leg of the X is broken. It is one of the leading causes of hereditary retardation.
Gail’s first son did not receive the gene. He is a high-achieving student and athlete. Her second son, Scott, has an IQ of less than 80, “I use the fragile X diagnosis to inform people so he can be better understood,” says his mom, “because the child that suffers most is the child who is misunderstood.”
Her third child, a daughter of 11, was born before the Heymans had a diagnosis of Scott’s condition, and although his sister, Carly, is not affected by the fragile X mutation, she is a carrier and will likely pass it to her own sons and daughters in an even more amplified state.
But there is hope. Though little can currently be done on the molecular level for her brother, physicians may one day be able to replace the abnormal DNA in Carly’s egg cells with properly functioning genes, forever ending the family inheritance of fragile X. Current experiments in gene replacement therapy are limited to manipulating DNA in human somatic cells, such as those in blood, bone marrow or organ tissue rather than the germ-line sperm and egg cells. But gene replacement remains medicine’s golden grail.
“It’s very hard to anticipate what might happen .. . say if something was set loose that had been genetically altered, something that has never existed before in nature…”
“The way we treat cancer today—and this doesn’t make my oncology friends very happy—is sort of like using a nuclear bomb to wipe out an anthill,” says Dr. Femhoff, referring to radiation and chemotherapy. “Where we are going to be 25 to 40 years from now … is that we will much more elegantly be able to say, ‘This is the specific gene or protein that has gone wrong.’ We won’t have to wipe out everything else in the process, and this will lead us to what scientists have been looking for for years: the magic bullet.”
For the immediate future, however, the greater promise of genetics lies in the development of new drugs. Recombinant DNA has already given us the first widely available supplies of human insulin, vaccines for hepatitis, blood clotting factors for hemophiliacs, human growth hormones for treating dwarfism and new therapies for cystic fibrosis. Simply understanding the role of DNA in disease will mean more precise diagnosis and better prescription of the drugs we already have.
Most major pharmaceutical companies are hiring geneticists at the top executive levels. Private biotech companies are doing their own sequencing of the human genome, rushing to patent newly discovered genes in the hopes of securing market rights to future genetic tests and therapies.
The stampede has many critics worried that a new generation of genetically engineered drugs will flood the market without proper scrutiny. Safety claims for new drugs will likely be based on genetically engineered animal models, such as mice that are specifically bred to develop human cancers. And those studies may be conducted in laboratory environments that are very different from conditions in the real world.
But it is gene patenting that most disturbs biotech critics. “Human beings are not machines. We are much more like what our religious traditions have maintained, in the sense that living organisms are so complex that the main thing you can say about them is that their essence is a mystery,” says Ronnie Cummins, campaign coordinator with the Washington-based, Foundation on Economic Trends, one of the nation’s most vocal critics of the biotech industry.
Last year, claiming that genetic technology represented “the new Genesis, the new Creation,” the foundation organized clergy from 80 different denominations in a press conference denouncing human and animal gene patenting. While the biotech industry cites a need to secure patents in order to attract private investors who finance the development of new technologies, critics argue that private industry should not be able to patent that which is found in nature—such as a gene or, say, an oak tree—and that doing so for profit degrades life.
To Emory’s Doug Wallace such arguments are overstated. “What I think biomedical technology has done is the converse,” he says. “It has taught us the beauty, the magnificence of the human animal and the human organism and through that given us an appreciation of our fellow persons and shown us that every human being is in fact biologically equal.”
Indeed, genetics shows that we each differ by a tiny, tiny percent of our genotype and that our seemingly huge differences in body type, skin tone or facial structure are in fact far less significant than our fundamental sameness. But it remains to be seen whether such a focus on our tiniest constituent parts—rather than on the whole human being—will prove great for medicine or just great for the medical industry.
Human growth hormone, for example, is a $300 million a year business. Two years ago Genentech, the sole producer of the genetically engineered human growth hormone Protropin, and Caremark, sole distributor of the drug, were named in an indictment concerning a kickback scheme to a Minneapolis physician who prescribed the drug. The Human Growth Foundation, a nonprofit that once had offices in Atlanta, formerly distributed to local elementary schools growth charts against which all children were measured. The shortest five percent were then sent home with notes suggesting that parents might want to consider a medical alternative. Genentech was a contributor to the foundation.
While industry touts potential future benefits from genetically engineered drugs, critics cite the L-tryptophan scare of several years ago in which a batch of the drug caused widespread illness and killed 27 people. It was a new, genetically engineered sleep aid and nutritional supplement from Japan. As for assumptions that to understand our genes is to understand our health, we have known the basic genetic component of sickle-cell anemia for decades, but there still is no cure.
“Genetic research is in its early stages, and one of the shames for those of us in the field is that we are not going to be here to look back and see, where did this all go?” says Dr. Fernhoff. “It’s always interesting to see which of the things that make the evening news had a real impact on society five years later. It’s a very small percentage.”
There probably is no better metaphor for society’s latent anxieties about genetic engineering than the plain garden tomato—subservient plant, sandwich lover’s rite of summer, inspiration for amusing sci-fi parodies starring vengeful killer fruit.
Two years ago the FDA approved the first genetically engineered food to be sold to consumers—the Flavr Savr tomato. The tomatoes don’t have to be sprayed with chemicals to extend shelf life. They can be enjoyed all year long and taste pretty good.
Nonetheless, consumer groups have railed about the FDA’s failure to require the labeling of genetically engineered tomatoes and other altered food products. Critics also have rallied opposition to such “transgenic” plants and animals around the argument that crossing a tomato with, say, a flounder to promote cold-climate tolerance is somewhat less than tasteful.
Scientists counter that genetic engineering is only shortcutting what agrarians and animal husbandry have been doing for hundreds, perhaps thousands, of years. However, traditional crossbreeding, hybridization and grafting are limited to closely related species.
“Genetic engineering is a totally different process, and the consequences and ethical ramifications are historically unprecedented,” says Dr. Michael W. Fox, vice president of The Humane Society of the United States and author of the book Superpigs and Wondercorn.
“If people are looking to science for their answers, if people are grounding themselves in science, then they are on a fast track.”
The first patent for a genetically altered animal was granted in 1988 for the “Harvard oncomouse,” a rodent researchers had genetically engineered with a predisposition for cancer. Since then, recombinant techniques have been used to create literally thousands of chimeric species (of diverse genetic constitution) for use in agriculture, forestry, environmental cleanup and biomedical research.
One such animal regarded with special dismay by critics is the transgenic pig, created by splicing human DNA into swine embryos. But pig organs, notably heart valves, have long been used in human transplant situations, and researchers hope that these genetically altered swine will produce organs that are more compatible with human transplant patients. The chimeric pigs have already proven viable enough to pass their altered genes to offspring, and the biotech industry hopes to have the first genetically engineered human/pig organs ready for harvest and transplanting by the end of the decade.
But what science can do may not always be what it should do.
For instance, does anyone really want to eat another organism that contains human DNA, an experiment that has already been tried in the lab? Genetic engineering can also transfer allergens from one species of plant to another, potentially presenting allergy sufferers with a whole new landscape of irritations. And what impact will the proliferation of chimeric plants and animals have on the integrity of nature’s wild species when they inevitably reproduce and migrate?
“It’s sort of like kids playing with matches,” says Atlanta author Lewis Regenstein, who has written several books on environmental contamination. “Some of these big chemical companies are very proud of their genetically engineered crops that they have designed to be resistant to their herbicides. Well, one of the things that restricts herbicide use is the killing power of the herbicide itself. It kills the crops, too. So now they can spray more herbicides on these herbicide-resistant crops, and the result is further contamination of the food chain and waterways with carcinogens.”
With herbicide-resistant plants, fish genetically better suited to acid lakes, microbes engineered to gobble up toxins, gene replacement therapy for cancers, and with the Department of Energy’s initial involvement in genome research because of its interest in the effects of radiation on humans, some wonder whether we will ever really clean the environment up or simply use genetic technologies to re-engineer life for survival on an increasingly poisonous planet.
“It’s very hard to anticipate what might happen … say if something was set loose that had been genetically altered, something that has never existed before in nature and for which there is no natural predator, and it started killing wheat and grain supplies around the world,” says Regenstein.
Few scientists totally discount such global what-ifs, but they insist that the possibility is remote. “There was a concern on the part of the scientists, not society, that we should look at this technology carefully and its implications. But after about 28 years, in fact, none of those concerns have proven to be a reality,” says Wallace. “Is genetic information inherently dangerous? Do we need to control it because we might be affecting our biological future?” he asks. “People are more likely to have read Mary Shelley’s Frankenstein than my paper on mitochondrial evolution. Our society is more concerned about imagined fears but has not been well versed in the reality.”
In that realm of imagination versus reality is the renewed interest in how genes influence human behavior. Countless media reports cite studies “linking” genes to a variety of traits such as homosexuality, criminality, obesity, alcoholism, intellect, novelty seeking, religiosity, political orientation, job satisfaction, leisure time interests and even propensity to divorce. An editor of Science, the nation’s leading peer-reviewed scientific journal, even declared in an editorial that the nature/nurture debate was now “basically over,” won by our genes.
“That’s garbage. We know the extremes of what’s nature and what’s nurture,” says Dr. Fernhoff, citing blood type and political orientation as two examples. “The rest of the stuff—personality and some diseases—are in the middle.”
Two of the most widely publicized areas of study have been the search for the so-called “gay gene” and research on a possible genetic component for violence. Criminal theorists speak of international DNA databases out of which society’s most violent criminals will be plucked like wilted pansies. A 1995 Harris poll shows that 56 percent of Americans surveyed would support such databases on a statewide level, which would contain genetic fingerprints of all newborn babies.
Gay researchers have asserted that evidence of a genetic component for homosexuality could foster understanding from others in society. Ironically, many in the gay community oppose such inquiries because of concern over the inevitable prenatal test and the fear that heterosexual parents would abort “gay” fetuses. Homosexual men and women might then retaliate by conceiving and discarding nongay embryos. Others wonder what an extremist government would do with knowledge of an individual’s sexual orientation, were it so easily acquired. And even if a gay gene were found, would it really change anyone’s mind about other people’s sexual practices?
To many the value of such research seems limited.
Similarly, in 1992 the National Institutes of Health was pressured by civil rights groups and others to withdraw funding from a proposed conference called “Genetic Factors in Crime.” Since blacks in the U.S. have a proportionally higher arrest rate for violent crimes, the implication, opponents argued, would be that blacks have a genetic predisposition to crime.
During a 1995 conference on the subject that brought together researchers and their critics, researchers themselves stated that finding something so simple as a crime gene would be absurd. The effects of poverty, a violent environment and the prejudices of legal and judicial system are also influences on criminal patterns. Rather, they said, behavioral genetics is simply a part of the overall quest for insight into human behavior.
“Personality traits are going to be tough because of the way they permeate society,” says Emory geneticist Steve Warren, co-discoverer of the fragile X mutation. “If you sought to eliminate manic-depression from society, would you somehow be affecting creativity, too? A lot of poets and artists suffer from manic-depression.”
But even if genes can be located for certain behavioral traits, it is still highly subjective as to how one defines the trait itself. In other words, what exactly constitutes mental illness, alcoholism, violence or an eating disorder? Sexuality is less likely to be an either hetero- or homosexual preference than it is to be a vast continuum of preferences.
So is this important science or a substitute for the harder task of eradicating societal influences on human behavior? Can genetics bring us closer together under the new light of our overwhelming similarities or drive people farther apart as we are shown our fundamental differences? Will genetics give us a better explanation of ourselves and others or an excuse for the way we already are?
“I think geneticists are beginning to realize that they can’t oversell themselves,” says Dr. Fernhoff. “If we oversell ourselves and the expectations, we are going to turn off our constituents. . . . And we can’t come up with some positive things if being able to test for a gene causes more problems than it solves. I think you are going to see a backlash, and I think in some areas you are already seeing that.”
For Janet Schatten, sister of Gail Heyman and co-director, with Heyman, of the Fragile X Association of Georgia, the issue isn’t what genetics bring to us so much as what we bring to it. “I don’t see any controversy with science providing information. If there is any controversy, it’s where are you relative to the universe. What is your grounding?” says Schatten, who is earning her master’s in Jewish studies. She has two boys with fragile X. “If people are looking to science for their answers, if people are grounding themselves in science, then they are on a fast track.”
To researchers like Doug Wallace genetics is, if not a fast track, then at least the straightest and steadiest one toward answering some of the most aggravating predicaments of the human condition. “The things that we are learning about human genetics now are the answers, the answers, the final answers to the problems that have plagued our species from its beginning. And they are the same problems that will plague people in the future. So, what is extraordinary about biomedical technology and specifically the Human Genome Project is that it is one of the few things that humans have ever had the opportunity to do where we are going to come to closure. We are going to get the answers,” he says. “And the answers will stand.” ✦