Should We Continue to Practice Genetic Engineering

As genetics allows us to turn the tide on human disease, it's also granting the power to engineer desirable traits into humans. What limits should we create as this technology develops?

Genes influence health and disease, as well as human traits and behavior. Researchers are just beginning to use genetic technology to unravel the genomic contributions to these different phenotypes, and as they do so, they are also discovering a variety of other potential applications for this technology. For instance, ongoing advances make it increasingly likely that scientists will someday be able to genetically engineer humans to possess certain desired traits. Of course, the possibility of human genetic engineering raises numerous ethical and legal questions. Although such questions rarely have clear and definite answers, the expertise and research of bioethicists, sociologists, anthropologists, and other social scientists can inform us about how different individuals, cultures, and religions view the ethical boundaries for the uses of genomics. Moreover, such insights can assist in the development of guidelines and policies.

Testing for Traits Unrelated to Disease

Much of what we currently know about the ramifications of genetic self-knowledge comes from testing for diseases. Once disease genes were identified, it became much easier to make a molecular or cytogenetic diagnosis for many genetic conditions. Diagnostic testing supplies the technical ability to test presymptomatic, at-risk individuals and/or carriers to determine whether they will develop a specific condition. This sort of testing is a particularly attractive choice for individuals who are at risk for diseases that have available preventative measures or treatments, as well as people who might carry genes that have significant reproductive recurrence risks. Indeed, thanks to advances in single-cell diagnostics and fertilization technology, embryos can now be created in vitro; then, only those embryos that are not affected by a specific genetic illness can be selected and implanted in a woman's uterus. This process is referred to as preimplantation genetic diagnosis.

For adult-onset conditions, ethical concerns have been raised regarding whether genetic testing should be performed if there is no cure for the disease in question. Many people wonder whether positive diagnosis of an impending untreatable disease will harm the at-risk individual by creating undue stress and anxiety. Interestingly, social science research has demonstrated that the answer to this question is both yes and no. It seems that if genetic testing shows that an individual is a carrier for a recessive disease, such as Tay-Sachs disease or sickle-cell anemia, this knowledge may have a negative impact on the individual's well-being, at least in the short term (Marteau et al., 1992; Woolridge & Murray, 1988). On the other hand, if predictive testing for an adult-onset genetic disorder such as Huntington's disease reveals that an at-risk individual will develop the disorder later in life, most patients report less preoccupation with the disease and a relief from the anxiety of the unknown (Taylor & Myers, 1997). For many people who choose to have predictive testing, gaining a locus of control by having a definitive answer is helpful. Some people are grateful for the opportunity to make life changes—for instance, traveling more, changing jobs, or retiring early—in anticipation of developing a debilitating condition later in their lives.

Of course, as genetic research advances, tests are continually being developed for traits and behaviors that are not related to disease. Most of these traits and behaviors are inherited as complex conditions, meaning that multiple genes and environmental, behavioral, or nutritional factors may contribute to the phenotype. Currently, available tests include those for eye color, handedness, addictive behavior, "nutritional" background, and athleticism. But does knowing whether one has the genetic background for these nondisease traits negatively affect one's self-concept or health perception? Studies are now beginning to address this question. For example, one group of scientists performed genetic testing for muscle traits on a group of volunteers enrolled in a resistance-training program (Gordon et al., 2005). These tests looked for single-nucleotide polymorphisms that would tell whether an individual had a genetic predisposition for muscle strength, size, and performance. The investigators found that if the individuals did not receive affirmative genetic information regarding muscle traits, they credited the positive effects of the exercise program to their own abilities. However, those study participants who did receive positive test results were more likely to view the beneficial changes as out of their control, attributing any such changes to their genetic makeup. Thus, a lack of genetic predisposition for muscle traits actually gave subjects a sense of empowerment.

The results of the aforementioned study may be surprising to many people, as one major concern associated with testing for nondisease traits is the fear that those people who do not possess the genes for a positive trait may develop a negative self-image and/or inferiority complex. Another matter bioethicists often consider is that people may discover that they carry some genes associated with physiological or behavioral traits that are frequently perceived as negative. Moreover, many critics fear that the prevalence of these traits in certain ethnic populations could lead to prejudice and other societal problems. Thus, rigorous social science research by individuals from diverse cultural backgrounds is crucial to understanding people's perceptions and establishing appropriate boundaries.

Building Better Athletes with Gene Doping

© 1997 Nature Publishing Group Grobet, L. et al. A deletion in the bovine myostatin gene cuases the double-mustard phenotype in cattle. Nature Genetics 17, 71 (1997). All rights reserved.

Over the years, the desire for better sports performance has driven many trainers and athletes to abuse scientific research in an attempt to gain an unjust advantage over their competitors. Historically, such efforts have involved the use of performance-enhancing drugs that were originally meant to treat people with disease. This practice is called doping, and it frequently involved such substances as erythropoietin, steroids, and growth hormones (Filipp, 2007). To control this drive for an unfair competitive edge, in 1999, the International Olympic Committee created the World Anti-Doping Agency (WADA), which prohibits the use of performance-enhancing drugs by athletes. WADA also conducts various testing programs in an attempt to catch those athletes who violate the anti-doping rules.

Today, WADA has a new hurdle to overcome—that of gene doping. This practice is defined as the nontherapeutic use of cells, genes, or genetic elements to enhance athletic performance. Gene doping takes advantage of cutting-edge research in gene therapy that involves the transfer of genetic material to human cells to treat or prevent disease (Well, 2008). Because gene doping increases the amount of proteins and hormones that cells normally make, testing for genetic performance enhancers will be very difficult, and a new race is on to develop ways to detect this form of doping (Baoutina et al., 2008).

The potential to alter genes to build better athletes was immediately realized with the invention of so-called "Schwarzenegger mice" in the late 1990s. These mice were given this nickname because they were genetically engineered to have increased muscle growth and strength (McPherron et al., 1997; Barton-Davis et al., 1998). The goal in developing these mice was to study muscle disease and reverse the decreased muscle mass that occurs with aging. Interestingly, the Schwarzenegger mice were not the first animals of their kind; that title belongs to Belgian Blue cattle (Figure 1), an exceptional breed known for its enormous muscle mass. These animals, which arose via selective breeding, have a mutated and nonfunctional copy of the myostatin gene, which normally controls muscular development. Without this control, the cows' muscles never stop growing (Grobet et al., 1997). In fact, Belgian Blue cattle get so large that most females of the breed cannot give natural birth, so their offspring have to be delivered by cesarean section. Schwarzenegger mice differ from these cattle in that they highlight scientists' newfound ability to induce muscle development through genetic engineering, which brings up the evident advantages for athletes. But does conferring one desirable trait create other, more harmful consequences? Are gene doping and other forms of genetic engineering something worth exploring, or should we, as a society, decide that manipulation of genes for nondisease purposes is unethical?

Creating Designer Babies

Genetic testing also harbors the potential for yet another scientific strategy to be applied in the area of eugenics, or the social philosophy of promoting the improvement of inherited human traits through intervention. In the past, eugenics was used to justify practices including involuntary sterilization and euthanasia. Today, many people fear that preimplantation genetic diagnosis may be perfected and could technically be applied to select specific nondisease traits (rather than eliminate severe disease, as it is currently used) in implanted embryos, thus amounting to a form of eugenics. In the media, this possibility has been sensationalized and is frequently referred to as creation of so-called "designer babies," an expression that has even been included in the Oxford English Dictionary. Although possible, this genetic technology has not yet been implemented; nonetheless, it continues to bring up many heated ethical issues.

Trait selection and enhancement in embryos raises moral issues involving both individuals and society. First, does selecting for particular traits pose health risks that would not have existed otherwise? The safety of the procedures used for preimplantation genetic diagnosis is currently under investigation, and because this is a relatively new form of reproductive technology, there is by nature a lack of long-term data and adequate numbers of research subjects. Still, one safety concern often raised involves the fact that most genes have more than one effect. For example, in the late 1990s, scientists discovered a gene that is linked to memory (Tang et al., 1999). Modifying this gene in mice greatly improved learning and memory, but it also caused increased sensitivity to pain (Wei et al., 2001), which is obviously not a desirable trait. Beyond questions of safety, issues of individual liberties also arise. For instance, should parents be allowed to manipulate the genes of their children to select for certain traits when the children themselves cannot give consent? Suppose a mother and father select an embryo based on its supposed genetic predisposition to musicality, but the child grows up to dislike music. Will this alter the way the child feels about its parents, and vice versa? Finally, in terms of society, it is not feasible for everyone to have access to this type of expensive technology. Thus, perhaps only the most privileged members of society will be able to have "designer children" that possess greater intelligence or physical attractiveness. This may create a genetic aristocracy and lead to new forms of inequality.

At present, these questions and conjectures are purely hypothetical, because the technology needed for trait selection is not yet available. In fact, such technology may be impossible, considering that most traits are complex and involve numerous genes. Still, contemplation of these and other issues related to genetic engineering is important should the ability to create genetically enhanced humans ever arise.

References and Recommended Reading

---

Baoutina, A., et al. Developing strategies for detection of gene doping. Journal of Gene Medicine 10, 3–20 (2008)

Barton-Davis, E. R., et al. Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proceedings of the National Academy of Sciences 95, 15603–15607 (1998)

Filipp, F. Is science killing sport? European Molecular Biology Organization Reports 8, 433–435 (2007)

Gordon, E. S., et al. Nondisease genetic testing: Reporting of muscle SNPs shows effects on self-concept and health orientation scales. European Journal of Human Genetics 13, 1047–1054 (2005) doi:10.1038/sj.ejhg.5201449

Grobet, L., et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nature Genetics 17, 71-74 (1997) (link to article)

Marteau, T. M., Van Duijn, M., & Ellis, I. Effects of genetic screening on perceptions of health: A pilot study. Journal of Medical Genetics 29, 24–26 (1992)

McPherron, A. C., et al. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387, 83–90 (1997) doi:10.1038/387083a0 (link to article)

Tang, Y. P., et al. Genetic enhancement of learning and memory in mice. Nature 401, 63–69 (1999) doi:10.1038/43432 (link to article)

Taylor, C. A., & Myers, R. Long-term impact of Huntington disease linkage testing. American Journal of Medical Genetics 70, 365–370 (1997)

Wei, F., et al. Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Nature Neurosci ence 4, 164–169 (2001) doi:10.1038/83993

Well, D. J. Gene doping: The hype and the reality. British Journal of Pharmacology 154, 623–631 (2008) doi:10.1038/bjp.2008.144

Woolridge, E. Q., & Murray, R. The health orientation scale: A measure of feeling about sickle cell trait. Social Biology 35, 123–136 (1988)

ericksonsorece.blogspot.com

Source: http://www.nature.com/scitable/topicpage/genetic-inequality-human-genetic-engineering-768

Share this post