Sunday reflections — perfect bodies
In our quest for the perfect baby and the perfect body, are we losing what makes us human? As genetic tests for disease risks are being created at lightning speed, can we trust that commercial interests in genetic profiling won’t bypass the integrity of the scientific process? Are such concerns justified? Have we considered the ethics of striving to create a genetically elite class?
Ronald M. Green, Ph.D., professor of ethics at
“Building Baby From the Genes Up”
Professor Green begins his article by portraying two young couples who wanted to use genetics in the selection of embryos for in-vitro fertilization that could eradicate breast cancer from their family lines once and for all. The idea sounded entirely reasonable, he said. In fact, on both sides of the Atlantic, embryo screening for serious genetic disorders is commonplace. This amalgamation of reproductive and genetic medicine has been named “reprotgenetics,” but is largely unregulated in the United States. In Britain, all requests for such procedures must be approved by its Human Fertilization and Embryology Authority, as he writes:
... What troubled the Human Fertilization and Embryology Authority was the fact that an embryo carrying the cancer mutation could go on to live for 40 or 50 years before ever developing cancer, and there was a chance it might never develop. Did this warrant selecting and discarding embryos? To its critics, the HFEA, in approving this request, crossed a bright line separating legitimate medical genetics from the quest for "the perfect baby."
Like it or not, that decision is a sign of things to come — and not necessarily a bad sign. Since the completion of the Human Genome Project in 2003, our understanding of the genetic bases of human disease and non-disease traits has been growing almost exponentially. The National Institutes of Health has initiated a quest for the "$1,000 genome," a 10-year program to develop machines that could identify all the genetic letters in anyone's genome at low cost.... With this technology, which some believe may be just four or five years away, we could not only scan an individual's — or embryo's — genome, we could also rapidly compare thousands of people and pinpoint those DNA sequences or combinations that underlie the variations that contribute to our biological differences.
... [W]e can intervene by means of embryo selection to produce a child with a reduced genetic likelihood of getting fat... No child would have to face a lifetime of dieting or experience the health and cosmetic problems associated with obesity. The same is true for cognitive problems such as dyslexia... Why should a child struggle with reading difficulties when we could alter the genes responsible for the problem?
Remember the 1997 science fiction movie, Gattaca? Its title was taken from the first four letters of DNA nucleotides: adenine, cytosine, guanine and thymine. Gattaca was a futuristic vision of a society driven by the new eugenics, where babies were created through genetic engineering to eliminate weaknesses and ensure they had the best hereditary traits. A genetic registry database used biometrics [upcoming post] to identify and classify those babies as Valid, and those who were conceived by traditional means were derisively known as In-valids. While genetic discrimination was illegal, in reality, it was easy to profile someone's genotype [talk about employer screening], resulting in the Valids qualifying for professional employment while the In-valids who were believed susceptible to disease were relegated to menial jobs. It was closer to reality today than might have seemed possible eleven years ago.
As Professor Green wrote today, Gattaca’s world was clean and efficient, but its eugenics obsessions “all but extinguished human love and compassion.” He went on to explain that these fears aren’t limited to science fiction:
Over the past few years, many bioethicists have spoken out against genetic manipulations. The critics tend to voice at least four major concerns. First, they worry about the effect of genetic selection on parenting. Will our ability to choose our children's biological inheritance lead parents to replace unconditional love with a consumerist mentality that seeks perfection? Second, they ask whether gene manipulations will diminish our freedom by making us creatures of our genes or our parents' whims... Third, many critics fear that reproductive genetics will widen our social divisions as the affluent "buy" more competitive abilities for their offspring... Will we re-create the horrors of eugenics that led, in Europe, Asia and the United States, to the sterilization of tens of thousands of people declared to be "unfit" and that in Nazi Germany paved the way for the Holocaust?
Finally, some worry about the religious implications of this technology. Does it amount to a forbidden and prideful "playing God"?
His [full article].
Dr. Kenneth Offit, M.D., MPH, with the Clinical Genetics Service, Department of Medicine, at Memorial Sloan-Kettering Cancer Center, New York, wrote a poignant Commentary article examining genomic profiling for disease risks in the March 19th issue of the Journal of the American Medical Association. The future benefits of genetic research are clouded by scientists and companies already behaving badly and demonstrating failure to resist the lure of commercial interests over scientific integrity.
Recently, there’s been an explosion of “commercial genomic 'tests' for diseases, conditions, traits and ancestry,” he writes. These companies advertise directly to consumers and claim they can identify genetic risks for various health conditions, including adult-onset diseases.
But the difference between these tests and conventional DNA research, traditionally introduced first to medical professionals before widespread marketing, he said, is that today, the commercialization of genomic profiling begins as a for-profit, direct-to-consumer marketing campaign, meant to bypass health care professionals.
Now, most physicians learn through the media of the availability of “genome scans” that can be ordered for about $1000 by their patients. These tests are touted to predict medical conditions from risk of obesity to risk of cancer, diabetes, and blindness. Health professionals are now faced with the prospect of their patients coming to the office, DNA profile in hand, asking for preventive management tailored to their specific disease risks.
But we have a long way to go until personalized medicine is scientifically supportable. Worse, these genomic tests have not been subject to prospective study and validation, physician education, and monitoring of laboratory quality by academic and regulatory groups, he said:
Direct-to-consumer marketing of genomic disease profiles seems to have escaped the careful vetting that accompanies the introduction of new biomedical technologies.
Professional organizations, such as the American Society of Clinical Oncology, began calling for certain requirements before genetic testing is introduced to medical practice. They identified an extensive list of problems that needed to be addressed before testing, of healthy people without symptoms, for hereditary risks for diseases. As Dr. Offit cautioned: “These requirements included addressing risk of insurance-based discrimination, validation of research data by prospective trials, and regulatory assurance of accuracy of testing.” What isn’t being communicated to the public is that “there remains a fundamental concern about the validity of many of the tests,” he said.
Assessing and comparing genetic testing quality between laboratories is not straightforward. The panels of disease-specific genetic markers used by some laboratories are proprietary and may vary between laboratories. The companies often state that the services offered are not medical tests because they are provided “for informational purposes only.” In some scenarios, the consequences of an incorrect genotype may be modest. For instance, in a widely reported example, one of the pioneers of genetic research underwent full sequencing and learned he had a genotype conferring lactose intolerance when, in fact, he did not have this condition.
The consequences of inaccurate genotyping for adult-onset disorders are enormous, as are the misuses of the information due to lack of understanding or exaggeration of its proven significance. Organizations such as the Institute of Medicine and the Genetics and Public Policy Center have warned of the dangers of introduction of genomic tests on a population-wide basis before regulatory and scientific requirements are met.
But concerns with genotyping errors isn’t just a matter of laboratory methods being inaccurate, as he explained:
Even if technically accurate, a genotype may lack clinical utility. For example, two of the discoverers of single nucleotide polymorphisms associated with macular degeneration do not consider these tests ready for clinical use... Commercial companies have proceeded to market panels of genetic markers, as well as whole genome “health scans,” which have largely been derived from retrospective studies. However, there is an emerging consensus that extensive replication across diverse population subsets is needed to discern true disease associations from the “blizzard of false positives” that is inevitable when hundreds of thousands of genetic markers are probed at the same time.
Despite these concerns, some academic institutions may be influenced by commercial pressures to market as-yet-unvalidated tests based on recent discoveries. The field is already replete with such initially promising but ultimately false-positive associations between genetic markers and schizophrenia, obesity, stroke, and Parkinson disease, for example. The reasons for the failure to replicate such studies include population heterogeneity, lack of statistical power, interactive effects, and technical issues related to genotyping.
The commercial companies are not unaware of the standards set by academic bodies; these standards are even cited in various “white papers” listed on some of the company websites. Nonetheless, the implicit marketing strategy of these companies is to involve the consumer in a “voyage of genetic self-discovery,” even if some of the initial paths charted lead nowhere. In the worse-case scenario, the paths may lead to unnecessary medical interventions or false reassurances and missed diagnoses.
The incentive for financial profit in such a journey is at fundamental odds with the skeptical nature of scientific inquiry and the conservative nature of clinical translation of new biomedical technologies.
Dr. Offit goes on to give examples of recent whole-genome studies of breast and prostate cancer risks where large studies had tested hundreds of thousands of single nucleotide polymorphisms in thousands of families and people with cancers not linked to known genes. The SNPs identified were associated with the most minuscule increased risk compared to the general population, raising questions of any real validity as a clinical measure for intervention or concern.
“The extent to which academic institutions will enforce existing ‘protective patents’ or will license newly discovered ‘risk SNPs’ for commercial use remains unclear,” he said. “As disease association tests have appeared, another industry has emerged: genomic testing of maternal and paternal DNA to learn of geographic ancestry. Such tests, however, provide a snapshot of only a tiny percentage of an individual’s genomic complement. Not surprisingly, the accuracy of these genealogic predictions is variable."
But currently, regulations of the genetic testing labs and the usage of genetic material are scarce. “All told, 25 states and the District of Columbia permit direct-to-consumer laboratory testing without restriction,” he said. Only 13 categorically prohibit it. But in states without regulations, there are few federal protections. Companies currently are under no requirement to support any of their claims about the accuracy or validity of their tests or conclusions.They are currently not reviewed by the FDA. [See consumer warnings about genetic tests issued by the FDA, FTC and CDC here.]
When breast cancer genetic testing was being debated a decade ago, the National Human Genome Research Institute and other agencies called for and supported prospective clinical trials to assess the psychosocial and medical effects of genetic testing for cancer risk. “Physicians and other health professionals in the field of genetic testing for cancer risk proceeded cautiously and, most would generally agree, responsibly,” wrote Dr. Offit. That responsibility is needed today with genomic testing for other disease risks to ensure the tests are reliable, accurate, clinically meaningful and safe, he said
Adding some of the most unsettling and thoughtful commentary in this issue of JAMA was Dr. Tony Miksanek, M.D., a medical author from Benton, Illinois, who reviewed Dr. Greene’s book, Babies by Design.
While hopeful about the future opportunities that might be made available in the burgeoning field of reprogenetics, he said, Dr. Green is not naive about the many qualms about how we can best ensure these new developments “are used humanely and do not escape our control.” Genetic engineering being used to cure diseases might be appropriate, but what about modifying risks or enhancing the human body?
Should improvement— boosting memory, augmenting physical prowess, and extending longevity—of already healthy people be tolerated, given the ethical and economic concerns? Already, attractiveness is the primary trait coveted by infertile individuals relying on egg and sperm donations to have children...
Genetic intervention has to focus on what is reasonably construed as being in the best interests of the child. Who can be trusted to determine what is reasonable? Even the role of parents in the setting of genetic modification is potentially problematic. Given the opportunity, what mother and father would not elect to have a child with an athletic build, excellent vision, strong teeth, and superior intelligence? Why not add a great complexion and nice hair, too? Genetic perfection can be thorny, though. How might a parent’s love and family relationships be affected if the designer child does not meet expectations? ... In the context of genetic engineering, does not such an attitude threaten a child’s freedom and curb his or her future identity?
Forthcoming genetic technologies will provide an opportunity to control human evolution. The possibilities and challenges are staggering. What exactly is it that makes individuals human? Is society willing to risk the formation of a genetically elite class—a genobility? Does society possess the humility, solidarity, and responsibility to handle genetic enhancements?
For heart-stopping considerations about the potential costs and a look at what society might have lost had the Human Genome Project been acted on years ago, watch this alternate ending to Gattaca.