Just five years into the projected 20-year Human Genome Project, remarkable discoveries have already been made about human genetics. We can link flawed genes to particular illnesses, including some forms of cancer. It is likely that we are on the verge of a brave new era in medicine, where serious disease will be cured by rebuilding our intricate genetic engines.
With this giant leap in knowledge comes a host of complex ethical, legal, and social questions that we will also have to answer to use this information wisely. Recognizing this, the U.S. government is devoting about 4 percent of the Project budget to examining these issues. And already, problems have begun to arise.
Testing for flaws in our intricate genetic engines
A few years
from now, a routine first visit to a doctor will probably include a blood sample. Not much is needed; a pinprick on the finger will be enough. Before leaving the office, a nurse hands you a consent form. You scribble your name on the dotted line without a second thought.
You might want to think twice: in that tiny droplet of blood is your genetic fingerprint, unique to you alone. But the 100,000 different genes you possess also reveal much about your children, your parents, and the ethnic group to which you belong. How should this information be used, and who should have access to it?
Dr. Kenneth Goodman, director of the Forum for Bioethics and Philosophy at the University of Miami, explains some of the not-so-hypothetical problems: "Suppose we discover an epidemiological correlation betwen a gene and a particular disease. Should we report back to the individual, or to a relative who might get the disease? That raises serious questions about confidentiality."
Personal medical privacy is likely to be ensured in the United States, protected by Constitutional guarantee. But for medical science to move forward, other information about you must become available for research; with that comes other risks.
"Even if a scientist promises to keep [your name and other personal] information secret, he still know where you live, your race or ethnic group, and other important demographic information," Goodman says. "What if science discovers that an entire group is at risk for a malady? Individuals could be redlined just because they belong to that group. [No one would sign] consent forms that state that a study could result in your race being discriminated against, or your demographic group stigmatized."
At present, cystic fibrosis is one of the few diseases that can be positively be linked to genetics. This illness demonstrates the complexity of such testing in most instances. About 70 percent of the cases are caused by a single mutation, and another 20 percent are the result of a handful of other genes. More than 200 different genes are believed responsible for the small percentage of remaining cases. And this is only for people of certain white, European descent; should a test for all these genetic mutations become available, it would be useless for Asians or African-Americans.
Even if a cystic fibrosis test were developed tomorrow and show that both parents carry the gene, it wouldn't guarantee that their baby would suffer from the disease. "In cases of clearly-defined genetic traits such as cystic fibrosis or phneylketonuria, it is often very difficult to predict whether the child or children of a couple will necessarily carry or show the condition," says Washington University Biologist Garland Allen.
Some exceptions exist; it appears likely that everyone with the Huntington's Disease gene will eventually develop the illness. But such cases are the exception, and generalizations can easily mislead. One newspaper headline proclaimed that a deafness gene had been discovered; only by close reading did it become clear that the gene was found among the members of one extended family in Costa Rica.
What is "normal?"
genetic information becomes available, Allen and others are concerned about the effects it might have on society. Every parent wants a perfect baby; will they choose abortion if genetic risks are found in prenatal testing? In one study, 22 percent of the population said, "a woman should have an abortion if the baby has a serious genetic defect."
Deciding what is genetically "serious" opens a Pandora's Box of unanswerable questions. "There are no definitions of 'health' and 'disease,' hence all the ethical conflict," explains Karen Greif, chair of the biology department at Bryn Mawr. "Some parents think that being short constitutes a disease state, and demand treatment of their child with growth hormone -- which is of questionable value. The U.S. public, with its obsession with physical perfection and general intolerance of disability, might be particularly vulnerable to stretching the bounds of what is 'disease.'"
This debate first flared on the national scene in 1993, when news stories reported that a researcher had discovered a "gay gene." Although these reports were wrong, much of the public didn't understand why geneticists vowed to keep a sex-orientation gene secret, if it were ever found.
"If the trait is a source of discrimination, should parents abort the fetus?" Asks Ronald Green, Director of the Dartmouth Ethics Institute. "If we permit parents to select out [fetuses carrying a gene for homosexuality], does it foster attitudes of exclusion for gays and lesbians? We're not going to be more tolerant of homosexuals because there's fewer of them."
Such questions plunge deeply into an ethically grey area, with no clear guidelines defining what is "normal." Ethicists like Green emphasize that they do not want to restrict research, but rather to use the knowledge well. And any information about genetic "defects" must be carefully balanced against the potential of what it will mean to that person's future. Green, for example, believes congenitally deaf parents should abort a fetus only because it does not carry the deafness gene, if they wish.
But even attempting to define "normal" is worrisome. Says Garland Allen, "We are all genetic defects in some ways, yet can lead very healthy and productive lives. For example, all human beings lack the ability to synthesize certain vitamins (B-1, for example), yet we get it by attending to a proper diet. Many forms of poor eyesight or poor teeth are genetic in origin, yet we wear glasses or get dental care, to compensate. Genetic forms of diabetes have been treated successfully with insulin injections. There are many possible solutions to bona fide genetic disorders. 'Genetic' does not mean inalterable."
Some of those solutions will probably within the lifespan of people whose genetic defects express themselves late. The woman with the rare BRCA1 gene has an 85 percent higher risk of developing breast cancer, but not until she reaches middle age. Alzheimer disease has been linked to several genes, but typically appears around age 70. Today's newborn might have gene therapies available by the time the disease appears.
"Today, the average age of death for cystic fibrosis is 29," says Green. "But a few years ago, it was adolescence. Do we select against this? If BRCA1 expresses itself at age 35 or 40, do you abort the child because you worry that somewhere down the line it will develop the problem?"
Also, warns Allen, "Many behavior defects claimed to be genetic have never been shown to have any significant genetic component whatsoever. It is important to first of all distinguish between those traits that have pretty conclusively shown to be genetic, and those that have not."
The risk of a new eugenics movement
a particular gene to a trait is difficult, particularly with mental illnesses. Twice researchers believed they had found genes associated with manic-depression, but subsequent investigation proved their results wrong, or at best inconclusive. Similar genetic associations with schizophrenia, alcoholism, and other clinically-recognized disorders have also failed. While genes likely play some role in mental illness, their contribution remains unclear.
"One of the problems with current studies in the area of behavior genetics is that human behavioral traits cannot be easily defined," Allen says. "Is schizophrenia or manic-depression a single behavior or a well-defined disorder? Many psychiatrists think the two many be different manifestations of the same problem. And what about criminality or homosexuality? None of these are single entities, like eye color, that can be unambiguously recognized by just about any observer. If we cannot properly define or identify a trait, we certainly cannot study its genetics in a rigorous or scientific way."
The need for conclusive proof of linkage is an important lesson from history. Deciding what is normal sketches a hazy line between disease and socially-unacceptable behavior. In the last century, genetics were thought to be responsible for social and economic problems such as criminality. Even poverty was believed to be the result of "pauperism," and that a "feeble inhibition" gene led to immoral behavior. As a result, laws were passed to keep ethnic groups from American shores.
"In the U.S. the consequences of this sort of genetic thinking enabled Congress to pass the 1924 Immigration Restriction Act, which preferentially excluded southern and eastern Europeans," explains Allen. "Those from the Balkans and Russia and those of Jewish descent were kept out because so-called genetic studies of the day had claimed that such people were genetically inferior in mental and social capacity. Such studies...gave a kind of scientific legitimacy to racist and xenophobic views [of that time]."
Dr. Goodman shares the concerns of many that genetics could be used again to justify political ends. "There's currently a debate about crime in the United States and, statistically, members of some groups are more likely to be arrested. Some people are claiming that such groups are somehow inherently more prone to crime. To try to wrap a genetic or epidemiological justification around such claims is just goofy science. [With this type of research] you don't necessarily get causality. It might point to a correlation, but we don't yet know if there is really a causal connection. All of these issues are shaped by scientific uncertainty."
(For more on the current attempt to link criminality to genetics, see the earlier news story in the Albion Monitor.)
The risks of explaining risks
the uncertainties of genetic risks to the public is another hurdle that must be passed. Example: studies show that a woman with the BRCA1 gene has an 85 percent higher risk of developing breast cancer. But this statistic does not predict she will have breast cancer; it only means that her risk is 85 percent higher than the normal population. Almost any risk factors can be improved by carefully watching diet, exposure to toxins, and other elements that contribute to the development of cancers.
"It's not only the general public that has trouble understanding genetic risks; many health professionals don't know what to do with the information either," Goodman believes. "Even geneticists don't have it easy communicating about genetic disease. One problem is that [genetic] information is different than other kinds of information about health, or future health.
"There are problems in explaining risk. If you overstate the risk, you panic people; if you understate it, people don't take the risk seriously. How do you communicate this information in a society where most people aren't even sure what a cell is?"
While a good explanation of our genetic risks would be one of the most important things we could learn from a doctor, it is also unlikely to happen, unless genetic counseling becomes widespread. "Right now, 95 percent of genetic testing is still done on pregnant women and fetuses," says Karen Rothenberg, editor of "Women & Prenatal Testing." "The general population is not interested in being screened."
Are these women given adequate and correct information? Rothenberg cites a 1992 survey of residents in obstetrics and gynecology, which found the doctors received failing grades on a genetic questionnaire, averaging only between 54 and 65 percent correct. She asks, "If the ob/gyn doesn't known all that much about genetics, who's doing the counseling?"
Rothenberg worries that we're creating a "genetic underclass" of people without access to genetic testing. But even if testing is done, providing adquate counseling to explain those risks will be difficult. Imagine that your doctor orders a profile for just 200 genes; even if five minutes were spent on each gene/disease association, it would take over 16 hours to explain them all. And it's theoretically possible for a disease to be associated with every single one of our 100,000 genes.
Communicating these risks also worries Maxwell Mehlman, Professor of Law and Director of the Law and Medicine Center at Case Western University. "The fashionable postion is that doctors should give people everything they want, but that can be a mistake with some information. We have to develop a way of explaing these risks to people, that they represent a host of possibilities that could happen sometime in their life. If we could do that, it would transform society."
Do you have a right to know?
is a crucial part of any genetic testing, but few guidelines currently exist. It is quite possible that home genetic tests could be made available, much as home pregnancy tests are now. When asked if it was possible that a private company could develop a "home breast cancer test" for the BRCA1 gene, one researcher remarked, "my guess is that somebody's working on it now."
Such a test would be fraught with danger. The results would probably be negative: although BRCA1 dramatically increases a woman's risk, this gene is only carried by about 5 percent of all women. Other genetic or lifestyle risks could be ignored by a woman given a false sense of security that she was safe from the disease.
Could such easily-misleading products be kept from the market? "If it can be done at all, it would have to be done with legislation," Mehlman thinks. "You might be able to prevent people from getting the test, but that creates a prohibatory environment, and we don't have a lot of luck in this country with prohibition. Another way is through [required] licensing by the Food and Drug Administration (FDA), but there's currently no way that anyone can say that a test harms the patient. As part of an FDA license, they could require warnings and clear instructions, and the company would be vulnerable to product liability suits if it was inadequate."
Mehlman and others see new laws controlling use of genetic information as inevitable. With hundreds of private companies seeking to profit from discovering genetic markers, there are no guarantees that such information will be ethically used.
"At present, any proposed gene therapy is subject to review and approval by NIH if federal funds are involved," says Karen Greif of Bryn Mayr. "However, it is possible that treatments might occur outside of federal oversight if private money is available. This has occurred with a controversial therapy for muscular dystrophy."
But even with ethical review of government-funded research and new legislation, proving a genetic link to a disease can lead to subtle, but critical, changes in medicine.
One growing concern is that society will abandon people already with the condition. This is happening today; one researcher was proudly told by colleagues that England and Scotland had "cured" spinal bifida. Did they have a secret not shared with the rest of the world? Not at all; the gene fingerprint for spinal bifida has been known for some time. But in those nations, any fetus carrying the gene is aborted, so no one is born with the disease. As a result, research interest in the painful and debilitating illness has dwindled, leaving the thousands who currently suffer with less hope of a cure.
What are "pre-existing conditions?
medicine, the genetic revolution will drastically change the insurance industry, according to a 1993 U.S. government study. Recommendations by the ethics panel included universal health-care coverage regardless of genetic information. The findings were opposed by the American Council of Life Insurance.
Thomas Murray, a founding member of Ethical, Legal, and Social Issues working group, describes the situation many are now beginning to face. "A nightmare scenario is that you get a genetic workup and find you're one of the people with the MSH2 gene [which causes about 10 percent of the cases of colon cancer]. Your insurance company says we'll cover you, but you're on your own if you get colon cancer. Is that what we want from our health insurance system? A better way would be to do away with this exclusionary system, [spreading the insurance risk] across the community to provide reasonable health care for everyone."
In one case cited in the study, a woman was denied health insurance after her nephew developed cystic fibrosis. She also was tested, and found to be a carrier of the gene. This does not mean she will develop CF; only that any children she might have would have an increased risk for the disease, and only if her husband likewise had the gene. The woman was told that she would not be insured if her husband was also a carrier. Because she simply wanted information about her own genetics, this woman spent several months without insurance coverage.
Other cases can be found where insurance was denied because genetics were considered a "pre-existing condition." Another example described an insurance company refusing to cover Huntington's disease for one man, even though he had no prior diagnosis.
Almost all genetic flaws could be considered to be pre-existing, even in diseases such as Alzheimer's, which may not appear until advanced age. If exclusions can be made on the basis of the codes in our genes, insurance will cover little more than broken bones.
But genetic risks are just part of the picture. "What's the most important factor in determining your cholesterol level?" Asks Murray. "Most people guess diet and exercise, but genes are far more important. You can help control your cholesterol levels, however, by watching what you eat and getting exercise. The world can't be divided into two buckets of genetic and non-genetic information."
companies will grapple with the connection between illness and genetics remains unclear. As the bookshelf of genetic information fills, we will have to answer all of these questions. No one wants restrict research; our ethical challenge to use this knowledge well equals, or perhaps surpasses, the challenges facing the biologists hunting the relationships between gene and disease. There will be no short answers, and no easy solutions.
"It's still bright and early in the morning for these problems," Dr. Goodman sighs. "This is still a young science, and we have to sort these questions out."
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