Margaret R McLean. Science, Religion, and Society: An Encyclopedia of History, Culture, and Controversy. Editor: Arri Eisen & Gary Laderman. Volume 1. Armonk, NY: M.E. Sharpe, 2006.
While cleaning out my mother’s garage, I came across a well-worn Time magazine. On the cover were two people, male and female, each entwined in a red double helix; between them, in yellow, were the words “The New Genetics: Man Into Superman.” The date was April 19, 1971. The associated story speculated about “the promise and peril of the new genetics”—correcting defects, avoiding the ravages of aging, increasing physical and mental ability, shaping Homo futurus. All this had become theoretically possible because of the work of scientists James Watson and Francis Crick, who had deciphered the double helical form of the macromolecule deoxyribonucleic acid (DNA) in 1953. Watson and Crick’s unraveling of the structure of DNA was world-shattering and has been likened to the publication of Charles Darwin’s On the Origin of Species and the smashing of the atom. In the now familiar twisted ladder of DNA resides the so-called “secret of life”—mechanisms of heredity, development, disease, and aging.
Although the “new genetics” described in the magazine merely promised what is now possible—in vitro fertilization, genetic testing, mammalian cloning—the religious and ethical concerns raised three decades ago are hauntingly familiar. Should “gene surgery” be confined to disease prevention and treatment or applied toward increasing the human life span? Should humans be “reengineered” with larger heads to accommodate more brain cells? Who, if anyone, ought to be cloned? Should we clone the FBI’s J. Edgar Hoover or basketball great Lew Alcindor? Such dilemmas, the article claimed, are rooted in the ever-present temptation for humans “to be like God.”
This ancient concern for hubris is a good starting point for a consideration of the Human Genome Project. Its modern incarnation is the frequent warning against “playing God.” Although some insist that we ought not “play God” and “fool with Mother Nature,” it is important to recognize that “Mother Nature” is constantly impacted by human activity. When we cut the grass or build a dam, we “fool” with nature. Genetic technology—like all human action—can be aimed at good or bad ends. Neither blanket acceptance nor outright rejection of genetic discoveries and possibilities is an appropriate or helpful response. Instead, we need to discern the ethical and scientific limits of genetic research and its applications. Of course, people of good will can disagree about how and where to set such limits, but that does not excuse us from the responsibility to try.
The Human Genome Project
In 1988, James Watson and others convinced the U.S. Congress to fund an international research project to decode “the human genome,” the estimated 3.2 billion letters of our genes. Spurred on by competition from Celera Genomics, this publicly funded Human Genome Project was completed in April 2003, surprisingly two years ahead of schedule and $400 million under budget.
The hereditary material of multicellular organisms such as humans is the double helix of DNA, which contains our genes. The double helix is found in chromosomes in the nucleus of a cell. DNA is made up of four chemicals, called bases, that when paired create the rungs of the familiar twisting ladder structure. Each gene is made up of these bases, in different orders and stretching different lengths. The bases—adenine (A), cytosine (C), guanine (G), and thymine (T)—make up the genetic alphabet, which provides information vital to the manufacture of proteins and to passing particular characteristics from generation to generation. Metaphorically, these four letters spell out the code necessary for making and operating a human being. If laid side by side, the letters of the human genome would fill 200,000 phone-book pages. Bases out of place, missing, or incorrectly duplicated can result in a genetic disorder, such as sickle cell anemia, cystic fibrosis, or Huntington’s disease.
Scientists deciphered the human genome by determining the sequence, or order, of all the bases in human DNA. They also made maps showing the location of genes along the chromosomes, much as a highway map shows the location of cities and towns along Interstate 80 from San Francisco to New York.
Somewhat surprisingly, only 2 percent of the human genome contains genes. The remainder—misnamed “junk DNA”—may be important to chromosome structure and regulation. The adjective “junk” should be seen as shorthand for “we don’t exactly know what it does just yet but we are working on it.” The Human Genome Project demonstrated that there are about 30,000 human genes. Taking us down a peg, scientists discovered that we have only twice the number of genes of the roundworm and triple those of the fruit fly. Over 200 genes have come to humans courtesy of bacteria, maintained across the billions of years that separate the two species in evolutionary time.
Human DNA can be likened to a molecular history book of the species that tells us about our origins in Africa and migration into Asia and Europe. Genetically, all humans are 99.9 percent alike. The remaining 0.1 percent—about 3 million out of 3 billion bases—makes us different. This minute genetic variation between people is part of what makes us look different: sex, eye color, and hair color, for example, are genetically determined. It also has a role in our susceptibility to disease and response to medicines. Certain genetic differences can increase our risk of illness. For example, the presence of the gene variant BRCA1 increases a woman’s risk for breast and ovarian cancer (although women may develop these cancers without having this variant). Other genetic variations directly cause diseases such as sickle cell anemia, hemophilia, and Huntington’s disease. Genetic changes, which produce such adverse effects, are called mutations. In some cases, a mutation in only one gene produces disease, as in Huntington’s disease. In many more cases, such as cancer, a disease is polygenic, being associated with multiple mutations in multiple genes at different chromosomal locations. Many variations in DNA occur relatively frequently and have no adverse effect on the individual. The ABO blood groups are an example of such benign variations called polymorphisms.
Scientists are building on the results and technological developments of the Human Genome Project to deepen our understanding of the genetic components of human health and disease. Genetics will assume an increasingly vital role in the diagnosis, monitoring, and treatment of disease. Within the next decade, it is likely that predictive genetic tests will allow us to know our individual risk for future disease and possibly to take preventative measures. It is also likely that we will know ahead of time how effective a particular drug will be based on our genetic profile.
All diseases have a genetic component, whether caused by a mutation or by the interaction between an individual’s genome and the environment. The Human Genome Project has pinpointed numerous genes that cause or are associated with disease. Over 4,500 diseases directly involve genetic factors. But having a genetic predisposition for a disease—breast cancer for example—is not the same as having the disease. A positive family history or finding a mutation associated with increased risk is no guarantee of future illness. At most, having a mutation that predisposes one to a certain disease is only one condition that, in association with other factors such as diet, exposure to ultraviolet rays, or cigarette smoke, may result in disease.
The long-term goal of the Human Genome Project is to use genetic information to improve human health by developing new ways to diagnose, treat, cure, and prevent disease. However, the path from diagnosis to treatment to cure is long and winding, and the journey has only begun.
A unique component of the Human Genome Project was the commitment of funds—$76 million through 1999—for ELSI, the “Ethical, Legal, and Social Implications” of this research. The project planners recognized that information gathered about the structure and function of human DNA would have deep implications for individuals, families, and society. Although such information may vastly improve human health, a number of thorny ethical, legal, and social issues surface. How should genetic information be gathered and used? Who should undergo genetic testing? Should testing be voluntary? Who should have access to an individual’s genetic profile? What constitutes misuse of genetic information? The ELSI strategy is extraordinary in that it identifies, analyzes, and discusses the ethical, legal, and social issues associated with genome research at the same time that basic research is being conducted.
Early on, the ELSI working group recognized that genetic diagnosis is not necessarily of benefit if there is nothing to be done, no surgery to undergo, no pill to pop. The completion of the Human Genome Project provides unprecedented opportunity for the development of genetic tests that can confirm or predict disease but can do nothing to treat or to cure. Finding a gene is not the same as finding a cure. Taking a test is not the same as being treated. The ELSI working group predicted that we might spend years living in this “interim phase,” a time when tests and diagnoses are plentiful but treatments and cures are few, a time when the most harmful consequences can occur, such as discrimination in employment or insurance and stigmatization.
The ELSI program focuses on how to make use of genomic information in an ethically, legally, and socially responsible fashion. Areas of concern can be put into three basic categories. The first consists of issues surrounding ownership of the genome, including gene patenting. The second focuses on genetic engineering—including reproductive genetic selection—and gene transfer therapy. The third considers the routine gathering and use of genetic information in research and clinical settings. Because this is where most people will first encounter genomics, two particular medical applications of the Human Genome Project’s findings merit attention here: genetic testing and pharmacogenomics.
The primary product of the Human Genome Project is not a new gizmo, but information—information of a deeply personal nature. Genetic information is increasingly being used to diagnose and predict disease. For example, all fifty states and the District of Columbia screen newborns for phenylketonuria or PKU, a metabolic disorder that causes severe mental retardation if not treated. Over 900 genetic tests are currently available, most of which are being used for newborn screening and in families with a history of a genetic disorder, such as Huntington’s disease or hereditary breast cancer. Nonetheless, it seems quite likely that genetic screening (testing an entire population such as newborns to identify those at high risk for a particular disorder or disorders) and genetic testing (testing a given individual or family) soon will be used to identify predispositions to gene-associated disease irrespective of family history.
But mainstreaming genetic testing raises the question of how this information ought to be used and who should have access to it. Should everyone be required to submit to genetic testing before marriage or starting a family? Should an individual’s genetic profile be used to set life and health insurance eligibility and premiums? Should employers be able to screen out those who are genetically predisposed to carpel tunnel syndrome or depression? In seeking answers to these and other questions, it is important to remember that, in many cases, genetic tests function more like a weather report than a crystal ball: they predict relative risk, not certain outcome.
It seems likely that medical records will soon contain not only cholesterol levels but also complete patient genomes together with a list of small genetic variations called SNPs (single nucleotide polymorphisms) that will be used to predict responses to medications. This genetic information will allow medications to be more precise, less burdensome, and more successful.
People respond to medications in different ways. Each year, over 100,000 Americans die from taking medicines that help most of us. Codeine relieves pain for many people but not for everyone. Scientists believe that creating drugs customized to a patient’s genetic makeup will result in safer drugs that work better. The knowledge gained from the Human Genome Project is being used to identify genes associated with different drug responses in different individuals. The hope is that medicines can be tailored for specific patient populations or individual patients, resulting in better and safer treatments.
Pharmacogenomics is a form of genetic testing that examines how individual genetic variations affect our responses to drugs. Such differences often occur in genes responsible for metabolizing a drug and can render a medicine ineffective or harmful. Certain genetic variations can speed up drug breakdown, resulting in undertreatment; others can slow down the process, leading to potential overdose.
Currently, if a medication is ineffective or not well tolerated, the dose is changed or a new drug is prescribed until the patient does better. Pharmacogenomics may allow prescriptions matched to an individual patient’s genetic identity, or genotype, minimizing adverse reactions and maximizing effectiveness. Genetically designed therapies promise more accurate dosing, shorter recovery times, and less risky drugs and vaccines.
Pharmacogenomics also has the potential to make more medications available to patients. Many drugs never make it to the pharmacy shelf because they work for only some people or they are lethal to some patients. With the ability to tailor drugs to a patient’s genetic profile, such medications establish a niche and reach only those patients who would benefit from and not be harmed by them.
The completion of the Human Genome Project has fueled hope for these “designer drugs.” Indeed, being handed a prescription specifically tailored to your drug metabolism genetic profile may be your first direct contact with the fruits of the Human Genome Project. Some have claimed that personalized medicine—“the right medicine, for the right patient, at the right dose”—is merely a matter of clearing a few scientific and regulatory hurdles. However, both pharmacogenomic research and its clinical applications raise ethical issues that deserve careful consideration.
Genetic testing for disease status or drug design in both research and clinical settings will require long-term storage and extensive use of genetic information, raising questions about privacy, consent, and confidentiality. During clinical trials, pharmaceutical companies and researchers collect and store genetic samples and data from participants. Is the storage of information for test development or pharmacogenomic research different from the storage of other medical information, genetic or not? Should research testing be done anonymously, thereby protecting participants’ privacy but denying them access to potentially important information about themselves?
When disease and pharmacogenomic testing moves into the physician’s office, there are additional concerns. Certain patients might find it more expensive or more difficult to obtain health, life, or disability insurance because they are predisposed to a disease such as Alzheimer’s or are “difficult to treat,” requiring, for example, a brand-name pain reliever rather than a generic. Should health insurance underwriters have access to genetic and pharmacogenomic test results? Ought drug response profiles and other genetic information be treated differently from other medical information such as lipid profiles or blood counts? Careful consideration of the costs and benefits to stakeholders —from individual patients to pharmaceutical companies to local and global communities—is needed.
It is known that disease prevalence varies within and among racial and ethnic groups. In the United States, for example, sickle cell anemia predominantly affects African Americans, while cystic fibrosis predominantly affects European Americans. According to geneticists, race is meaningless on the molecular level. Race and ethnicity are largely nonbiological ideas confounded in the United States by a history of prejudice. But scientists and physicians find it helpful to classify patients by age, sex, and race. Despite significant genetic variation within and between racial groups, there is good evidence that members of different races respond differently to some drugs. An example is the genetic variant CYP2D6, which renders 7 percent of European Americans immune to the pain-killing effects of codeine but affects only 1 percent of Asians.
Practically speaking, the likelihood of finding some genetic variant within one racial group but not within another can influence the design of clinical trials and drug development. Designing medicines or developing tests for a particular racial group while denying diagnosis and treatment to another is problematic from both scientific and ethical points of view. In addition, care must be taken to avoid using race or ethnicity as an excuse not to test. It could be wrongly assumed that every member of a particular racial or ethnic group would have the same genetic variants and thus the same predisposition to a disease, or that all members of the group would react to a given drug in an identical manner. Even greater care must be taken to treat people fairly. Genetic insights should not be allowed to prop up erroneous views of genes and race and to violate human dignity by deepening patterns of stigmatization and discrimination.
As genetic research continues and genetics enters routine medical practice, religiously and ethically informed views are important for raising concerns and shaping public policy. Religious points of view, informed by long traditions of ethical reflection, can sharpen moral vision by raising questions of meaning and purpose often overlooked by secular ethics. When people of faith express concerns about treating people with respect, about potential misuse of technology, or about the effects on the poor and marginalized, they speak for many. Religious traditions and ethical systems emphasize over-arching values such as human dignity, justice, and the common good, and thus have a great deal to offer our private conversations and public debates about genetic technology.
We have only just begun the age of “the new genetics” promised in that 1971 Time magazine, and we are not so much in an era of genetic revolution as genetic evolution. Scientists are building on the Human Genome Project to learn more about human health and disease. But as exciting and compelling as the genomic future appears, that future must include attention to domestic and global health disparities. While considering a future resplendent with “designer drugs” and “personalized medicine,” it is important to remember that health is a social responsibility. It is not only about me and mine, but also about us and ours. It is a matter of human dignity, justice, and the common good. Access to and distribution of basic health care are ethical challenges worthy of the same intensity of purpose and support as the Human Genome Project.