Human Genome Project’s first draft is months away, but is your hospital ready?
Public will demand new genetic tests, therapies
The Human Genome Project, a joint effort by the National Institutes of Health (NIH) and the U.S. Department of Energy, is expected to complete a draft sequence of the human genome by the spring of 2000, almost two years ahead of schedule. Establishing the sequence of all of the estimated 80,000 to 100,000 genes in human deoxyribonucleic acid (DNA) will allow scientists to detect which genetic mutations are linked to disease, develop tests for the mutations, and eventually develop therapies for treating and preventing conditions with genetic causes.
When this research is publicized, you can expect the public to deluge your facility with demands for new genetic tests and therapies. It’s not too early to start preparations.
The short answer is that the medical community still has some time before the information gathered by the researchers dramatically affects the health care environment. However, the complete sequence and map of the genome will lead to the development of new genetic tests and therapies on a faster and unprecedented scale. In addition, there are significant issues that health systems and ethics committees need to begin considering now.
"The genomic sequence is a tool that researchers can use to understand the genetic contribution to diseases — schizophrenia, heart disease, etc., so the primary impact of having the working draft sequence, and then the complete sequence, will be in biomedical research, initially," explains Kathy Hudson, PhD, assistant director for policy and public affairs in the office of the director at the National Human Genome Research Institute (NHGRI), the arm of the NIH that oversees the project.
"Clearly, the immediate ramifications are going to be the ability to identify which genes are involved in diseases. Historically, we have been able to do that for one gene at a time for diseases that have monogenic causes, which is where a mutation in a single gene leads to the disease. The new challenge and opportunity is to be able to understand the more common and also more complex diseases and their genetic contributions and their relationships — one gene to another and also the environment or various environmental factors that in combination can lead to disease. That is more complicated and will take more time," explains Hudson.
So exactly what is it?
The Human Genome Project was launched in 1990. Research centers around the world are participating in the project and sharing information as it is discovered. Administered and funded by both federal agencies, the project’s mission is to "map" or find the location of genes on the human DNA chromosomes and "sequence" those genes, identifying what proteins are linked together in what way for each gene.
Sequencing the genes allows researchers to distinguish mutations in individuals whose DNA differs from the gene sequence the majority of the population has. The project was initially expected to take 15 years. However, technological advances in the methods genes are sequenced and mapped have allowed scientists to complete the project faster.
A recent NHGRI press release announced that one quarter of the genome information already is in the public domain, available on publicly accessible databases set up and maintained by the project.
"We are going to have 90% of the genome, the estimated 3 billion base pairs in our genetic instruction books, sequenced and in publicly accessible databases in the spring of this year, spring of 2000," says Hudson. "That sequence will be 99.9% accurate. Our goal for the complete sequence is to have 100% of the genome completed in a form that is 99.99% accurate."
The entire sequence, at 99.99% accuracy, is currently expected to be complete by the year 2003, still ahead of schedule. However, due to the rapidly advancing nature of the project, Hudson says she believes that date also will be moved up.
"We haven’t revised that date yet, but I expect that it will be moved up as well, as more and more information continues to come out of the [research] centers," she says.
Data available now
Even though the draft sequence of the genome is not expected to be complete until next spring, investigators will not have to wait until then to obtain the information. "As the sequence is coming out of the sequencing production facilities, it is being deposited nightly into the databases," says Hudson.
According to the NHGRI, the databases are updated each time an assembly of 1,000 to 2,000 genetic base pairs is obtained. Researchers at institutions around the world can go into the Internet database, known as the GenBank (www.ncbi.nlm. nih.gov/Genbank), access the information and even add information they’ve obtained through research.
"At the recent Society for Human Genetics meeting, this researcher talked about finding the gene for a relatively rare birth defect," Hudson explains. "He was able to localize where the alteration was by looking at families that inherited forms of this condition. But, once he knew approximately where the gene was on the chromosome, then he was able to go to the publicly available sequence, he found his gene there and it was already sequenced."
The National Library of Medicine keeps statistics on the site about how many searches are done of the data and how much information is in the database at any given moment, she adds.
As researchers continue to use the information in GenBank to determine which genetic mutations affect disease development, new genetic tests will be developed to screen for diseases.
This will put pressure on the medical community to decide how to offer this new technology to the public, and many health care providers are not comfortable with genetic information and genetic testing, says Alan Guttmacher, OD, a medical geneticist who is senior advisor to the director for clinical affairs at the NHGRI.
"There is no question about that. Many health care providers from various branches, not just physicians, are in this sort of unusual position right now," he says. "They do not completely understand genetics, and they generally have not been trained in it very much. Now they are uncomfortable because we are beginning to perceive that, instead of this peripheral area of medicine, it can be a very important part of medicine and something that they need to use on an increasing basis in their practice."
According to an article in the Nov. 4, 1998, Journal of the American Medical Association,1 a recent American Medical Association survey found that 59% of the American public are somewhat or very likely to take advantage of genetic testing, and 72% believe their primary care physician can interpret the results.2
However, another study of physicians3 revealed that the participants misinterpreted one-third of predictive test results for colon cancer, and fewer than 20% of their patients received appropriate genetics counseling. (For more on public input regarding genetic testing, see story, p. 141.)
Educational efforts for providers are key
Efforts are under way in several states to increase providers’ knowledge about genetics and genetic testing.
Before coming to the NHGRI, Guttmacher pioneered an ongoing statewide educational effort in Vermont that attempts to educate the medical community and the public about advances in genetic technology and its potential impact upon health care.
"Our grant was for something called the Community Genetics and Ethics Project, an effort to get people around the state talking about the ethical, legal and social implications of medical genetics," he relates. "As part of that, we had a series of retreats for different kinds of groups, from members of the public to health care providers. For example, the second of those was for hospital ethics committees. We had about 15 or 20 people who belonged to hospital ethics committees come to a two-day retreat to talk about these things and listen to case scenarios."
Efforts like the Vermont project are funded through a part of the Human Genome Project known as ELSI (ethical, legal, and social issues).
"At the outset of the project, both the Depart ment of Energy and the National Institutes of Health agreed to set aside 5% of their budgets for the Human Genome Project to fund studies of the ethical, legal, and social implications of the research," says Hudson.
As the results of the studies funded through ELSI come in, the data are funneled through the office of public policy at NHGRI, which interprets the findings and develops public policy recommendations, she continues.
"In addition to that, we, together with the American Nurses Association, American Medical Association, and about 120 other health professional organizations across the spectrum, have joined together into what is known as the National Coalition for Health Professional Education in Genetics," she says, "and that coalition is attempting to address key needs that are applicable to clinicians, not specific to nurses or physicians or one discipline, but across the whole spectrum."
Guttmacher says intimidation regarding the science of genetics is hindering many hospital ethics committees in beginning to talk about the ethical implications of these advances.
"I think, to be honest, one thing that ethics committees need to get past is being paralyzed by the science of this and think, My gosh, we are going to have to make case-based ethics decisions or give advice about genetics, and to do that, we really have to understand DNA and all of its base pairs and how everything relates,’" he says, "but people do not need to do that. Sure, they need to have some familiarity with the basic concepts of genetics, but they do not need to be laboratory scientists. They don’t need to be able to replicate DNA to be able to make very societally appropriate decisions."
Ethics committees do need to educate themselves about what genetic testing is available and what the tests are able to do and not do, in order to educate their providers and the people whom the health system serves, Guttmacher says.
"It is important that we not have just geneticists talking to geneticists and ethicists talking to ethicists and occasionally a geneticist talking to an ethicist," he emphasizes. "But, if this is going to have the wide-ranging societal impact that we think, obviously we need to get a lot of people thinking about these things and caring about this before that happens."
References
1. Karanjawala ZE, Collins FS. Genetics in the context of medical practice. JAMA 1998; 280:1,533-1,534.
2. Mitka M. Genetics research already touching your practice. American Medical News April 6, 1998.
3. Giardiello FM, Brensinger JD, Petersen GM, et al. The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. N Engl J Med 1997; 336: 823-827.
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