Unless you've spent the past decade hiding under a rock, you've probably heard the hype about how breakthroughs in genetics will transform medicine, and life, as we know it. Well, if you're still a doubter, you better start getting used to the reality of the genetic revolution.
Hang onto a little bit of skepticism, if that makes you feel better. After all, most of us aren't flying personal helicopters to work, as some futurists predicted earlier this century. But take note that it was basic scientific research conducted only a few decades ago that made possible semiconductors, digital computers and the Information Age we take for granted today. Most gene watchers fully expect a similar bounty of clinical breakthroughs to sprout from the decades' worth of fundamental research in genetics.
What's in store?
For starters there will be exquisitely sensitive and inexpensive genetic tests that will provide people with blueprints of their DNA, detailing their personal risks for rare diseases and common killers. Some already exist, such as tests for specific breast cancer risks, but by 2020 few diseases will be able to hide the genetic factors that help them fell their victims.
Already scientists are using genetic tools to gather insights into the causes of diseases, allowing the design of powerful new drugs and custom-tailored uses of old drugs.
Researchers are also working on fixes for genetic mistakes, some that directly repair "broken" DNA and others, in the form of drugs, that supply missing ingredients needed for healthy living.
Even if some of the hot leads prove to be dead ends, there's little doubt that genetics will transform medicine in the next millennium as antibiotics did in this one (See related story, p. 14).
Signposts for the road ahead are already popping up like mushrooms after a summer rain:
* Dolly the sheep has been cloned from a cell scraped from the udder of her "mother."
* Sizzling progress has been reported on the decoding of the entire DNA sequence of humans, a project which is expected to yield a working draft of all human genes by next spring -- years ahead of schedule.
* The genes behind some diseases, such as cystic fibrosis and schizophrenia, have been discovered.
Some people worry that genes, all 80,000 that make us human, are the same as destiny. For better and for worse, that's simply not so. True, some genetic defects inevitably cause illnesses, such as Huntington's Disease, a rare and intractable killer best known for claiming the life of folk singer Woody Guthrie.
But genes have varying forms and usually operate in groups to influence human health, meaning that a particular defect in one or more genes might predispose rather than predestine someone to developing heart disease or a particular kind of cancer. Genes, then, are not often a death sentence so much as they are a wake-up call. Armed with specific knowledge about their risk for colon cancer, for example, people might be more inclined to change their diets, get regular exams and perhaps someday take drugs that would repair their genes.
Targeting the top killers
Right now the most advanced kinds of genetic screening are available for relatively rare diseases. But the work on the human genome project plus wide-ranging research on the genetic basis of more common diseases will intersect to yield a voluminous and highly specific hunting list in the years ahead.
Consider that by some estimates genes were a significant factor in nine of the top 10 killers in 1996 (See chart, p. 11). In 1997, the most recent year for which data are available, the rankings of the top seven killers remained unchanged. AIDS dropped to No. 14, replaced at No. 8 by suicide. Kidney disease was the ninth leading killer. Chronic liver disease held the No. 10 spot.
Family history, a polite way of saying genes, has long been acknowledged as vital information to figuring the risk for dying from the big three: heart disease, cancer or stroke. Even accidents, No. 5 on the list, might have a genetic component in the form of predisposition to take risks, says Alan Guttmacher, M.D., senior adviser to the director of clinical affairs at National Human Genome Research Institute, National Institutes of Health, Bethesda, Md.
People can debate the extent of genetic determinism, but the role of genes is critical to understanding most of the chronic diseases that matter.
"It's not just luck that some people smoke their whole lives and don't develop heart disease, lung cancer or anything else," Guttmacher, a board-certified pediatrician and clinical geneticist, told healthcare executives gathered at a meeting this summer of the National Committee for Quality Health Care held at Northwestern Memorial Hospital in Chicago.
Highly specific diagnostic tests are the first dividend from the genetic mapping. The DNA that is our genetic library uses pairs of complementary chemicals called bases as the text in the book of life. A single genetic defect in one of the three billion bases in the human genome can spell disease. As Guttmacher puts it, one spelling error in the equivalent of 23 sets of the Encyclopedia Brittanica can trigger a hereditary disease. It sounds next to impossible to detect something so rare, but the technology to ferret out those defective genes is here today and will only get better with time.
The bigger challenge may be sorting out the effects of many genes that are benign in some combinations, mildly problematic in other and deadly in a few.
In any event, the depth and breadth of genetic knowledge that will soon be available raises plenty of ethical concerns.
Will insurers have access to the information, perhaps refusing to cover people whose genes spell trouble? Will insurers or employers be able to require genetic testing? What about those people who prefer to live their lives the old-fashioned way, oblivious to the risks encoded in their DNA? Personalized genetic information will provide doctors a tool with practically unfathomable clinical power. But the unprecedented specificity and predictive ability of DNA data cut two ways. DNA decoded can cure in some hands or be used to blacklist in others.
One thing's for sure, ethicists and genetic counselors will have to work double time to keep up with the technologists.
Already the early adopters in the population have started looking for genetic help, and you guessed it, they're turning to the Internet.
"We've seen a greater awareness of genetic issues with patients," says Christopher Friedrich, M.D., an associate professor of medical genetics at the University of Pennsylvania School of Medicine, Philadelphia.
Friedrich, an expert on the genetic factors that contribute to heart disease, welcomes the rapid advances in knowledge but worries about how limited resources will be allocated to fight health problems.
"With one drop of blood you can get a picture of the person at all these different genes, and that may be helpful in convincing people to take preventative measures," he says.
But our capacity for analysis, he adds, hasn't kept pace with all the genetic data that's pouring in. "Which (genes) are really significant and which ones aren't?" he asks.
Almost every disease does have genetic factors, he concedes, but patients can't change them -- at least not yet. Therefore, Friedrich recommends that genetic approaches be applied selectively and cautiously for the time being.
Despite the worries that decoding the human genome could open a modern day Pandora's box, the truth of the matter is we humans are all in this together.
Nobody's perfect when it comes to genes. Everybody has good ones and bad ones. That basic and humbling fact ought to provide some comfort to all of us as scientists unravel the secrets of life.
"We're all mutants," quips the NIH's Guttmacher. "There's not one of us who's normal."