Thursday, July 01, 2004

Bioethics: Is Enhancement Right?

Wondergenes: Genetic Enhancement and the Future of Society

By: Valerie Gray Hardcastle Ph.D.

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By now we all know that the large, red, smooth tomatoes we purchase at the grocery store are genetically enhanced so that the plants from which they came produce tomatoes that are larger, redder, and smoother than before. We read in the newspapers of scientists altering the genes in experimental mice so that they are born with the propensity to develop cancer or some other chronic and debilitating illness, or they are born resistant to these same diseases. In the back of our minds, we hope that the scientists engaged in these sorts of procedures do no harm.

But what if we had the capacity to make similar changes to humans? What if we could alter our own genes so that we could run faster, think better, work more efficiently? Should we make these changes? These questions engage Maxwell J. Mehlman in his book Wondergenes: Genetic Enhancement and the Future of Society. He considers the social and personal implications of potential human genetic engineering, asking after the costs and benefits to our values, our beliefs, and our future. Mehlman concludes that there is a strong possibility genetic engineering will change the very fabric of our society, and he champions significant governmental oversight, regulations, and bans to control all-but-inevitable abuses. 

Is his analysis correct? Is governmental red tape the only thing standing between us and a genetic Armageddon? In the end, I must conclude that, no, it is not. Like Mehlman, I see a host of complex scientific, legal, and ethical challenges ahead of us, but I also see how technical and human realities will preclude the sort of future that Mehlman predicts. 

THE GENETIC CODE

To understand the implications of genetic enhancement, we must first understand how our genetic code works. Balled up in the nuclei of our normal human cells are strands of DNA (deoxyribonucleic acid), which form our chromosomes. Human DNA contains a chain of about three billion base pairs that form the rungs of the double helix “ladder,” and the particular sequence of the base pairs determines our traits. DNA works by constructing various proteins. Some sequences of tiny bits of DNA base pairs contain instructions for building amino acids, the building blocks of proteins. These proteins then make up our tissues and control our biochemical processes. Other sequences of DNA base pairs tell the coding sequences when to turn on or off, while additional sequences seem to sit there with no function at all. 

Sometimes errors creep into our genetic codes. These errors can lead to specific diseases and disorders. For example, people with cystic fibrosis are missing three DNA base pairs that code for one of the amino acids that goes into the protein that helps transport chloride around the body. As a result, their lungs fill with mucus and their pancreas does not function normally. Other diseases that result directly from genetic hitches include Huntington’s disease, Tay-Sachs disease, and sickle cell anemia. But not all genetic disorders are that straightforward. Often a genetic error must work in tandem with other errors and with environmental factors to lead to disease. Many cancers seem to operate this way. In these cases, genetic defects raise the probability of some disorder but do not directly cause it. 

Because scientists now have mapped the human genome sequence almost in its entirety, we are starting to learn more about what our base pairs code for and how they work. This knowledge, in turn, should lead to much better control of our own DNA, control we could use not only to help cure disease but also to enhance otherwise healthy people. 

Mehlman describes four recent advances in genetic science. Each advance brings with it not only potential benefits but troubling ethical questions about the balance between personal liberty and government intervention.

 ADVANCES IN GENETICS

Mehlman describes four recent advances in genetic science. Each advance brings with it not only potential benefits but troubling ethical questions about the balance between personal liberty and government intervention. 

Forensic Genetics

Forensic genetics allows us to identify people by using their DNA. About 10 percent of our DNA varies from person to person, and we can use these differences to distinguish among people, just as we use differences in fingerprints to identify people. Scientists can use the areas of our DNA that do not appear to code for anything— so-called “junk DNA”—to identify kinship relations. If two samples of DNA show the same repeating patterns in these areas, then it is likely that these two segments are from the same person, or a close relative. We now use these techniques to identify unknown bodies, to determine a suspect’s guilt or innocence, and to establish paternity, among other things. The U.S. military, the Federal Bureau of Investigation, and most states have created DNA banks, which store DNA samples taken from military personnel and convicted felons. 

States and organizations follow their own guidelines for collecting DNA. Initially, states only collected DNA from convicted sex offenders. Now, some states collect DNA from all people convicted of misdemeanors and felonies, and three states collect DNA from all people arrested on felony charges. Mehlman sees many questions arising from this use of DNA. How long should these samples be kept? What about DNA from juvenile offenders? Is it acceptable to collect DNA from everyone in the vicinity of a crime? Should we take and store samples from everyone at birth? Could DNA collected for one purpose—testing for a genetic disorder—be used for another— searching for a criminal? In this era of terrorist threats, how much of our right to privacy do we wish to cede in the name of greater security? 

Genetic Information

In addition to learning how to identify people based on their DNA, we have experienced a revolution in our ability to test strands of DNA to learn more about the specific characteristics of people or groups. With the development of high-speed, automated sequencing, we now can uncover a person’s entire genetic profile in fairly short order. We already know, for instance, that people with more than 26 repeats of the genetic segment that makes the protein huntingtin will inevitably develop Huntington’s disease in adulthood. We also have tests that are less definite, but provide indications. For example, certain genetic alterations indicate an increased probability for various cancers. 

The question is what to do with this information. How much information should people get about their own genetic profiles? What information should be available to spouses before making a decision to have children? If a couple learns that their child has a genetic disorder of some sort, Tay-Sachs disease, Down’s syndrome, or merely a cancer marker, is abortion a good option? Should employers or insurance companies have access to this information, and could they use it to require people to take preventive measures to decrease their chances of developing a chronic disorder? 

Genetic Therapies

With our increasing knowledge about genetic profiles and their implications for our personal characteristics, we are developing better genetic therapies. For example, we now know how to synthesize human growth hormone instead of relying on what we can collect from cadavers. In addition, we are starting to insert corrective genes into defective DNA in the hope of curing chronic and debilitating diseases. Thus far, the results are mixed. Altering genetic profiles so that they actually and only promote change for the better turns out to be exceedingly difficult. Altering genetic profiles so that they actually and only promote change for the better turns out to be exceedingly difficult. 

UNETHICAL BEHAVIOR VERSUS UNANSWERABLE QUESTIONS

Before I address the fourth and final recent advance in genetic science described by Mehlman, I should call attention to a problem that seems to run through this book. Mehlman does not distinguish between two types of ethical concerns. Some concerns raised by new medical advances in genetic science are not specific to the gene therapies themselves. For instance, scientists are required by law to report deaths and other difficulties associated with clinical trials to the Food and Drug Administration (FDA). But in at least one case neither the FDA nor the universities who ran the tests reported their results to the public (which was not required) or to the National Institutes of Health (which is only required if federal funds are involved). As a result, the public and other scientists have scant knowledge of what might be going wrong in the trials and, thus, little basis for making informed decisions about whether to continue with any particular therapy. There appear to be cases in which potential financial gains led people to act immorally and irresponsibly. 

Here we have an example of an ethical concern or dilemma that confronts us because good and not-so-good people sometimes behave badly in medical research. Scientists might not report failures in clinical trials because that would mean the end of their funding. Pharmaceutical companies might falsely promise miracle cures to the desperately ill in order to make a profit. We know what is right and how to respond because the ethical concern is not new in principle; it simply arises in a new context or application. 

But there is a different type of ethical concern which arises when new technologies create new possibilities and call for decisions to which we might not know—even in principle—how to respond. The questions raised by forensic genetics and genetic information are representative of this type of concern. It is important that we keep these two types of ethical challenge separate. In one, the technology allows people to act wrongly. In the other, the technology itself raises questions that, no matter how good our intentions, we do not know how to answer. I see the latter as presenting a genuine ethical conflict; the first does not. 

On the one hand, how and whether the government should regulate a new, powerful technology is truly a difficult question, and thoughtful and well-informed folk can genuinely disagree over the right course of action. This is one reason why abortion, stem cell research, and bioengineered foods are so controversial. On the other hand, when the question is how best to protect innocent people from the unscrupulous, while preserving what is good about the scientific research itself, the case is often clearer. Here, thoughtful people generally feel some intervention is necessary, although they might differ over how best to obtain the right outcome, by the government or some other means. Mehlman often conflates the two instances, seeing both as calls for the same sort of analysis and intervention. But an ethical question just is not the same as a policy question, even when both involve the implications of new technologies. 

GENETIC ENHANCEMENT

Genetic enhancement, the final “advance” Mehlman discusses, is still in its infancy. With genetic enhancement, we use what we know about genetic alterations to change healthy people for the better. We are not curing anything, but we are expanding our normal human capacities. 

Of course, as Mehlman points out, it is often unclear what counts as an enhancement as opposed to a therapy. We can inject human growth hormones into abnormally short people and they will grow to within one standard deviation of normal. This is considered therapy. But if we inject the same growth hormone into a normal-sized person hoping to create a basketball player, then clearly we are enhancing. But what if we inject the growth hormone into a slightly short woman so that she grows to be slightly taller than average? Is this therapy or enhancement? The line between therapy and enhancement is blurry and therein lies one difficulty Mehlman sees with our latest genetic advances. He thinks we should support genetic therapies but be wary of genetic enhancements. 

To explain this reaction, we must understand what he sees as the future of genetic enhancements. We already spend a considerable amount of time and money enhancing ourselves in various ways. We educate our young, we work out at the gym, we lift our faces, and we excise our fat. But, says Mehlman, all these changes are relatively small compared with what we could do if we had greater control over our genes. 

Here, I must interject that Mehlman has his facts wrong when he notes that weightlifters who take steroids can improve their bench press by only about 17 pounds. As a competitive weightlifter myself, the difference I see between the top performers in natural competitions and those in untested competitions (where steroids can be used) is about 150 to 200 pounds in the bench press—for both men and women. Thus, the differences we can make by using chemical enhancers actually can be quite remarkable. In addition, as the recent drug scandals indicate, athletes now have access to performance-enhancing drugs that are undetectable by any known blood or urine analyses. 

But, let us suppose that current enhancements change our performance or appearance only a little and that we always can tell when someone has had something enhanced. How might genetic enhancements be regarded? One possibility—the one I favor—is that genetic enhancements would simply be viewed as additional tools in our arsenal of self-improvement to achieve basically the same ends we already seek through other means. 

How might these genetic enhancements be regarded? One possibility —the one I favor—is that genetic enhancements would simply be viewed as additional tools in our arsenal of self-improvement to achieve basically the same ends we already seek through other means.

Mehlman has a different view. He sees a “transformed society,” in which “increases in strength, stamina, and endurance go... beyond world-class athletic norms. Cognitive enhancements could produce virtually unlimited increases in intelligence, memory, and other cognitive abilities...Genetic enhancements might even significantly lengthen one’s lifespan, perhaps even give people eternal youth.” 

Moreover, we could get all these changes at once, and “by permitting individuals to alter dramatically a large number of traits, genetic enhancements could give them enormous, perhaps decisive, advantages over others.” Indeed, Mehlman believes that genetic enhancements “might produce individuals who deviated so substantially from current population norms that the result would be a new species of life on the planet. A species that is far stronger, handsomer, and more intelligent, and that quite possibly would live forever. A species that is no longer human.” 

COMPLICATIONS OF INDEFINITE ENHANCEMENT

Is he right? I think it is easy to get carried away with science fiction notions of infinite change for the better. But it is exceedingly difficult to change one trait without affecting others; at bottom, we really are finely crafted and well-balanced biological machines. 

Let us suppose we want to create a new breed of tall humans. Suppose we isolate the genes that control when our bones stop growing and can turn them on and off at will. Suppose further that we decide to delay turning them off so that we can create a group of super basketball players. Would this work? Nature, of course, has already experimented for us. Humans whose bones continue to grow beyond normal bounds have all sorts of physical difficulties. Not surprisingly, taller-than-average people have more problems with their bones and joints. They are subject to greater physical injuries because their longer bones provide for greater leverage. People with acromegaly, a condition that results from an overabundance of growth hormones, often suffer from high blood pressure and cardiovascular disease, muscle weakness, joint pain, sleep apnea, arthritis, polyps, osteoporosis, diabetes, and vision abnormalities. Larger bones in humans restrict the functioning of the nerves inside the bones and the functioning of the heart, lungs, and other internal organs outside the bones. In short (so to speak), we did not evolve to be much taller than we are now. Our systems interlock and overlap so that if we change one physical characteristic, we disrupt the overall healthy balance of our structure. 

As with many things in life, we can have too much of a good thing. A story currently in the news tells about a young boy in Germany who has a genetic mutation that promotes extreme muscle growth. His DNA blocks production of the protein myostatin, a chemical that limits muscle growth in mammals. Now four years old, this boy can already hold two 7-pound weights with his arms extended, something many adults cannot do. 

Researchers have artificially created similar mutations in mice for several years and are hopeful that knowing the protein behaves the same way in humans will lead to treatments for muscular dystrophy and other muscle-wasting diseases. No doubt some people will also use this knowledge to make muscle-enhancing drugs. But this mutation is not without significant dangers. Increasing muscle size means increasing the size of all muscles, including the cardio and digestive system. Doctors expect that the young boy in Germany will develop heart and other problems as he grows up. We cannot simply take a genetic therapy for some disorder and assume that it will have an unproblematic enhancing effect on people without the disorder. 

NEUROETHICS

When we think about enhancing the brain, we run into even more complications. Our brain structure is determined by an intricate interplay between environmental stimuli and genetic development. Our genes contain a rough blueprint for the various structures in our brain, but its final form is shaped almost entirely by environmental stimuli. There simply is no simple gene-trait correlation for anything like intelligence or sociability. To change those traits will require more than just greater control over our genes, and, frankly, we cannot even begin to imagine how to go about such things. 

Our genes contain a rough blueprint for the various structures in our brain, but its final form is shaped almost entirely by environmental stimuli. There simply is no simple gene-trait correlation for anything like intelligence or sociability. To change those traits will require more than just greater control over our genes. 

We humans evolved over many years to function well in our niche. We probably are not the best we can be, nor are we ideally suited to life on Earth. At the same time, we are pretty darn good, and it would be hard to move us outside the developmental limits Nature has already established without wreaking havoc. It is my contention that genetic enhancements, if we get them at all, are not going to work in the way Mehlman envisions, even in the distant future. Technical difficulties in our biologies simply preclude it. Whatever enhancements we will muster in the future will either change us only slightly—within the bounds of normal—or with accompanying unpleasant side effects. Although these side effects might not prevent the determined from enhancing their bodies or brains in some way, they will prevent enhancements from becoming too widespread or integrated into our society. Genetic enhancements in the latter half of the 21st century will not be like liposuction is today. 

ETHICAL DILEMMAS AND POLICY CONCERNS

But suppose I am wrong. I cannot foresee the future any more than Mehlman. Suppose he is right, and we figure out how to harness our genetic code so that we can create all sorts of fantastic enhancements. What should we do then? 

Mehlman is unequivocal in his analysis: Ban what you can and regulate what you cannot. His reasons are several. First and most obvious are concerns about harming the innocent. If we permanently alter our gene line, then our children are doomed to suffer the consequences of the changes. Given the recent demise of Dolly, the first cloned mammal, and our other cloning failures, making genetic changes clearly carries with it unpredictable results. 

Personal autonomy is also a concern. Even if we do not foist enhancement on our children, there might be social pressure to participate. Compare this possibility with breast augmentation surgery. In the entertainment industry, oversized breasts are now the norm, and most starlets must surgically enlarge their breasts to be competitive. What if other industries, either directly or indirectly, pressured their employees into having some particular genetic enhancement? How could one refuse and yet remain competitive? 

For Mehlman, these questions become more pressing once we realize that not everyone will be able to afford enhancements, even if they want them. He thinks we will devolve into a world of haves and have-nots, where the differences between the two groups are extreme (even if they aren’t different species). How can we preserve equal opportunity in a world where only some have all the opportunity? 

At the same time, Mehlman worries about issues of authenticity. Similar worries arise in sports today. Many athletes take performance-enhancing drugs to run faster, swim farther, lift more, or cycle more efficiently. But most of us believe that sporting competitions should take place among so-called natural athletes, using their innate skills and talents, and we judge that chemical enhancements are a form a cheating. Of course, our position here is inconsistent, because we think it is acceptable to use external aids not available to all competitors —faster shoes, lighter bikes, sleeker swimsuits, excellent coaches, and high-tech training facilities. Be that as it may, in the artificial and arbitrary world of sports, we have decided that physical enhancements are okay, but chemical enhancements are not. Similarly, Mehlman believes that just as athletes should not be internally enhanced, neither should we in our daily commerce, for to be enhanced is not to be authentically human. 

Mehlman’s view of the future of unrestrained enhancement is bleak: 

Great rewards will go to those who can afford the most extensive enhancements, rather than to those who earn by determination and hard work. Under relentless pressure from employers and peers, anyone who can afford to become enhanced will have no choice but to do so, and wealthy parents will invariably enhance their children to give them success in life. The genetically enhanced will use their exceptional skills to take advantage of the unenhanced. Equality of opportunity will be replaced by the rule of genobility. Democracy will die. 

But notice that Mehlman’s world happens only if people behave badly. Enhancement technologies themselves would not open new avenues for misbehavior; they would just allow us to do more of what we were doing before. There is no prima facie reason to assume that the genetically enhanced would take advantage of the unenhanced, any more than there is to assume that those with Ivy League educations take advantage of those without. As with most groups, some people behave well and some do not. Some take advantage every chance they get; others would never do so. 

Nothing in what Mehlman tells us leads me to conclude that these enhancements would offer us anything other than more of what we have now. The questions are not new—they are not genuine moral dilemmas. Rather, they are the same old questions of how to keep bad people in line while not infringing on personal or civil liberties.

Indeed, looking at how people react to enhancements already available is instructive. Some embrace enhancements for various reasons, whereas others prefer to remain natural. These two groups develop different moral sensibilities. The enhanced are instrumentalists; they believe that enhancements fully justify the ends. The anti-enhanced are more Kantian in their approach; they believe that being “pure” is nobler than being artificial. Mehlman falls squarely into the latter category. I cannot see any logical reason to prefer one way of thinking over the other; it seems more a matter of aesthetics than anything else. I also cannot see why these reactions would not carry over to genetic enhancements; some would embrace them, others would not. 

The possibility of genetic enhancements does raise interesting questions. However, nothing in what Mehlman tells us leads me to conclude that these enhancements would offer us anything other than more of what we have now. The questions are not new— they are not genuine moral dilemmas. Rather, they are the same old questions of how to keep bad people in line while not infringing on personal or civil liberties. This might be an interesting challenge, but it is not one that only genetic enhancements give us.

EXCERPT

From Wondergenes: Genetic Enhancement and the Future of Society by Maxwell J. Mehlman. © Maxwell J. Mehlman. Reprinted with permission of University of Indiana Press.

Genetic enhancement could represent a transcendent evolutionary step in which mankind finally seizes its biological destiny from its former molecular masters, the genes. Hitherto, mankind, along with most other forms of life, has served primarily as a host for genetic parasites, who inhabit the cell nuclei and employ their hosts for reproduction. Having preprogrammed the degradation of its telomeres, they abandon the parent for its more useful offspring, leaving the former to die and be recycled. Genetic enhancement, then, appears as a mighty instrument of deliverance. It allows the host to seize control, to finally turn the tables on the genes and liberate itself from their tyranny. 

Indeed, we have already begun to do this. We are producing forms of life that have never existed before. Bacteria that are engineered to consume and biodegrade oil spills. Chimeras called “geeps” that are half goat and half sheep. A mouse that grows a human ear on its back. Frogs and rabbits with glow-in-the dark pigments. But the full fruition of genetic engineering will not be dumb, single-celled organisms or odd-looking little critters. It will be creatures that are articulate and self-aware, with minds that are highly—indeed fantastically—intelligent. 

They will not be like us. 

But since not everyone will be able to obtain genetic enhancements, some of “us” will still be around. 

So what happens if we wake up someday and discover that the planet is inhabited by more than one sentient species? 

This could be big trouble. 

As the members of the superior species look down on the unenhanced, they may decide that the unenhanced, while clever little creatures, do not deserve the same civil and political rights. Driven by disregard or contempt for their unenhanced forebears, the superior species may become callous, malevolent slave-masters. They may even decide that they have no further use for the unenhanced. Except perhaps to toy with them. 

In short, we could wake up someday and find that we have created a race of monsters. 

The ancient Greeks had a term for this: for exceeding our grasp, for thinking that we could mimic the Olympian deities. They called it hubris… According to the Greeks, hubris, the delusion that one can achieve what is reserved for the gods, causes harmartia, or miscalculation. This in turn leads to nemesis, or catastrophe. 

Obviously, the creation of a race of highly intelligent, genetically enhanced monsters would be folly of a grave sort. It would go far beyond the concern that genetic engineering deprives children of their “natural” genetic destinies, or that germ line manipulation would corrupt the gene pool so that humanity would be too homogenized to be able to confront a new environmental insult. 

But that is not even the greatest folly. Nor is it entirely unfamiliar. After all, the Holocaust stemmed from the Nazis’ belief that they were supermen and that Jews were subhuman. 

No, the ultimate horror of genetic enhancement is not that we will create monsters. It is that we will create gods.



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Carolyn Asbury, Ph.D., consultant

Scientific Advisory Board
Joseph T. Coyle, M.D., Harvard Medical School
Kay Redfield Jamison, Ph.D., The Johns Hopkins University School of Medicine
Pierre J. Magistretti, M.D., Ph.D., University of Lausanne Medical School and Hospital
Robert Malenka, M.D., Ph.D., Stanford University School of Medicine
Bruce S. McEwen, Ph.D., The Rockefeller University
Donald Price, M.D., The Johns Hopkins University School of Medicine

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