Designer Genes
How the Human Genome Project could change your life
 
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Beyond the Human Genome Project

While researchers speed to finish the map of the human genome, many secrets remain locked in the DNA. At least one organization—the Cure Autism Now (CAN) Foundation—has mobilized to hasten the answer to one genetic conundrum: What gene or genes cause autism?

In a scientific world where labs compete for resources and discoveries are patented for proprietary use, CAN has chosen a more congenial, collaborative approach. It has established the Autism Genetic Resource Exchange (AGRE), a repository of DNA resources from families that have more than one member affected with autism spectrum disorders.

The project’s goal is to make a large collection of genetic material available to numerous researchers who can all look for the genes that cause autism, and ultimately find a cure, said Marianne Toedtman, MN, RN, family coordinator of AGRE. “The way in which we felt we could move things along much faster is to have these materials readily available [to the entire scientific community],” she said.

Toedtman coordinates enrollment of families in the project. The families do the Autism Diagnostic Interview—a standardized test—and have their blood drawn. The samples go into the genetic repository, identified only by a unique identifier code to keep names confidential. Researchers can apply to the scientific steering committee to gain access to the genetic bank. So far, the repository contains samples from 140 families, and another 250 family samples await processing. Toedtman said that three research labs are now using AGRE resources.

“Once they’ve found out where things have gone wrong, what pathway’s depleted or overworking or whatever, then you can say based on this, let’s create a pharmaceutical that intervenes,” Toedtman said. If researchers can achieve that, she said, they’ll have unlocked from the genes the secret to the elusive cure for autism.

For more information call Marianne Toedtman at the AGRE project, (888) 288-4762.

~ Anne Federwisch, OTR
   

By Anne Federwisch, OTR
Photo: PhotoDisc
September 13, 1999

The Human Genome Project may be the first government endeavor to finish ahead of schedule since the effort to put a man on the moon. Researchers expect to figure out the sequencing of all the genetic material in our DNA by 2003—two years earlier than expected. But even after 13 years of research, $2 billion in funding, and many consequent genetic discoveries, there will be a lot we still don’t know and even more we still can’t do.

Part of the knowledge deficit has to do with sheer numbers. Although the twisted double helix of DNA is composed of just four unique molecules (adenine, thymine, guanine, and cytosine), the strands include about 3 billion base pairs, in different combinations and orders, and around 100,000 genes. And knowing where all the genes are won’t tell us what they do.

Health professionals’ roles

But the Human Genome Project has already begun to affect nursing care, according to certified genetics counselor Janet Williams, PhD, PNP, RN. “We engage in health promotion and disease prevention and symptom management,” she said. “What the Human Genome Project has done for us is help us be more clear about what some of those genetic factors are [influencing health] and what one might do if you knew that information.”

For example, an extensive protocol has been written for health professionals to help patients undergoing testing for Huntington’s disease deal with the emotional consequences of finding out they carry the gene, William said. Like many disorders, Huntington’s leaves patients in a therapeutic gap, she said. It’s possible to determine that patients carry the gene, but researchers haven’t figured out yet how to counteract its effects.

As genomics (the study of genes and how they work) advances, nurses’ knowledge needs to keep pace, said certified genetics counselor Eileen Rawnsley, RN, executive director of the International Society of Nurses in Genetics. “There hasn’t been a lot of genetic information in the basic nursing education,” she said. With the field of genetics changing almost daily, nurses need to read and take classes to keep up, she said.

A long way to go

Despite the progress, completing the Human Genome Project won’t mean we’ll have all the answers, stressed David Witt, MD, a medical geneticist with Kaiser Permanente Santa Teresa in San Jose, Calif. “It means that all the genes will have been sequenced, but it still means you have to figure out what they’re doing and how they fit into the whole scheme of normal physiology and disease,” he said.

Even the diagnostic tests already available aren’t 100 percent effective, Witt said. “We don’t know all the mutations to look for, for example. Or a particular disease may result from a problem in more than one gene,” he said. “It isn’t the godsend. It isn’t perfect.”

Revolutionary potential

Despite the limitations, experts think unraveling the secrets of the genome will be key to combating disease in the years to come. Genetic differences likely explain why some people are susceptible to cancer, hypertension, or heart disease, said Terry Sharrer, PhD, curator of health sciences at the Smithsonian Institution in Washington, D.C. The organization is co-sponsoring a conference titled “Gene Medicine: Using the Map” this week in the nation’s capital.

“Gene medicine in the next 25 years has the possibility of bringing mortality [of cancer and heart disease] down to about what pneumonia is today,” he said. If that breakthrough becomes a reality, Sharrer said, “we will have done in the next century something equivalent to what happened in this century when antibiotics were largely responsible for knocking down infant mortality.”

Gene therapy

One of the most hyped advances is gene therapy, replacing a person’s faulty DNA with a corrected version in an effort to cure disease. “The whole idea of gene therapy sounds great,” Witt said. “A real sexy topic, but it’s really only been tried successfully in a very few limited diseases.”

The first attempt at gene therapy was in 1990 on a girl with severe combined immune deficiency syndrome due to the lack of a specific enzyme, Sharrer said. Although the girl is now an active, healthy teen-ager, she still needs treatments every three years or so. Sharrer estimates that a couple thousand patients have been treated with gene therapy for a host of diseases, but because patients have also received other treatments, “you can’t say so far there have been any uncontested successes [with gene therapy].”

Yet an upcoming trial in gene repair shows promise, Sharrer said. Researchers plan to treat children with Crigler-Najjar syndrome, in which the lack of a liver enzyme that breaks down bilirubin causes severe jaundice and eventual death. An injection will contain a substance that triggers the body’s own genetic repair kit to fix the harmful mutation. “If it works, and those kids do turn pink, it will be the first time that medicine has ever corrected a human disease at its point of origin,” he said.

Matching drugs to genes

Another promising area is pharmacogenomics, the study of how a person’s genetic makeup influences his or her response to medication. “The more we understand about our own genetic programming, the better we will be able to understand why some people are more likely to benefit from a medication, whereas another person might have some undesired side effects,” Williams explained.

Any of the cancers as well as any genetic disease is a potential candidate for pharmacogenomics, said Gillian Woollett, DPhil, MA, associate vice president for biologics and biotechnology for the Pharmaceutical Research and Manufacturers of America. The promise of pharmacogenomics is to design new drugs that have a specific indication for a particular genetic population instead of one-size-fits-all drugs. To date, there are about 350 biotech medicines in development, Woollett said, but pharmacogenomics hasn’t put any drugs on the market yet.

What’s right in a brave new world?

Each genetic advance brings ethical questions. In fact, one of the goals of the Human Genome Project itself is to look at the ethical, legal, and social issues that may arise from the availability of personal genetic information. “There’s a real concern about discrimination with regard to health insurance, life insurance, and employment,” Williams said.

But discrimination isn’t the only concern. “Those of us who practice clinical medical genetics deal with it [ethics] literally on a day-in, day-out basis,” Witt said. Issues include prenatal testing and subsequent abortion, quality-of-life questions, and confidentiality concerns. For example, if you find out that a person has an inherited medical disorder, does the rest of the family have a right to know—even if the patient doesn’t approve of disclosure?

In a much larger realm, some people fear that genetics could be used to create a “super race” or to select for desirable personality traits, not just as a weapon against disease.

Sharrer does not think that the Human Genome Project and other genetic discoveries have unlocked a Pandora’s box of genetic tinkering with evil intentions. He has faith in researchers to do the right thing. “The real Pandora’s box is 520,000 cancer deaths this year. Twice that many coronary vascular deaths,” Sharrer said. “All technology has a price. This [advances in genomics] is the only way we’re going to make substantial progress against the diseases that are killing us.”