The Global Implications of Genomics

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Wouldn’t it be nice to know whether a diet rich in steak and buttery dishes, punctuated with a nice fat Romeo y Julieta cigar every night, would really kill you or your loved ones before your allotted time? Or whether you have a particular combination of genes that make you especially vulnerable to, say, diabetes? In the not-very-distant future, ordinary individuals will be able to buy maps of their own DNA that indicate their susceptibility to chronic diseases. Such maps would allow people to know at a young age whether they are genetically predisposed to life-threatening ailments, and thus could take measures to avoid them.

That was one of the heartening expectations that two of the world’s leading geneticists, Pascal Goldschmidt and Jeffery Vance, shared in a panel session titled “The Global Implications of Genomics” during the University of Miami Global Business Forum Jan. 15 – 16, 2009. Goldschmidt is senior vice president for medical affairs and dean of the University’s Miller School of Medicine. Vance is professor and chairman at the school’s Dr. John T. Macdonald Foundation Department of Genetics.

Geneticists used to think that the upper end of the human lifespan was genetically limited to 120 years. The latest genetic research indicates it’s about 150 years, according to Goldschmidt. But most people still don’t get much past 70. Why? It’s in your genes.

“We are all born with a susceptibility for chronic illnesses,” Goldschmidt said, then rattled off the most notorious ones, including cancer, cardiovascular disease, diabetes, respiratory disease, depression and joint disease. “All of these illnesses have a genetic background, that is, something in the gene pool that predisposes an individual to develop a chronic illness.”

On the screen behind him, Goldschmidt showed a shocking cross-sectional photo of a coronary artery that was almost totally clogged. He noted that its 28-year-old male owner’s cholesterol levels were not alarmingly high. Moreover, the man was a tremendous athlete: world champion figure skater Sergei Grinkov of Russia. “It was a total surprise that an individual with this profile would have this problem,” Goldschmidt said. Grinkov had a fatal heart attack in 1995 before he had turned 29.

The point is that genetics studies now could warn people like Grinkov that they have a propensity for fatal heart problems or other conditions that elude cruder indicators, like cholesterol levels and lipid profiles. “Chromosome 9, in particular, seems to be a player in cardiovascular disease,” Goldschmidt noted, adding that researchers have also found that Chromosome 3 is “an interesting center” for cardiovascular disease. “So we’re really getting good at defining which genes increase your risk of cardiovascular disease and dying young.”

Genomics can also tell us if we are among the fortunate ones whose cell repair mechanisms are formidable enough to prevent cells from becoming cancerous. “Some people are born with a great cellular repair mechanism, so they can smoke, they can eat steaks every day, they can smoke cigars at age 95, and tell you it’s the right thing to do,” Goldschmidt noted. But many are not so lucky, and genomics can provide them with the bad news so that they can take steps to avoid getting sick. For example, if someone knows his genomic profile indicates a tendency to develop lung cancer, he could do all he can to avoid cigarette smoke.     

In other words, genomic medicine has great potential to reform the business model of medicine, making it less about reacting to illnesses and more about preventing them. “The real purpose is to try to prevent disorders from occurring,” Vance told the audience at the outset of his talk. When they do occur, individualized therapy based on an individual’s genetic information will help doctors find “a straighter course” to the right treatment, avoiding unnecessary, time-consuming tests and diagnoses. “One of the great pie-in-the-sky goals of genomic medicine is pharmacogenetics, the right medicine for the right patient,” he added, noting that “a large percentage of drugs don’t work for everyone.”

Vance said that if there were just one thing he could get across during the sessions, it would be an understanding that there are two forms of disease genes. One, which he said comes from “old genetics,” is the idea that a single gene causes a disease, such as cystic fibrosis or sickle-cell anemia. The other, from “new genetics,” is what he called a “susceptibility gene.” Such genes make an individual more susceptible to a disease but don’t cause it directly. To illustrate the concept, Vance showed a slide depicting a balance scale holding three weights of different heaviness, or riskiness. Each weight represented a “risk gene.” The presence of one of them wouldn’t lead to a disease, but the presence of all three eventually would.

Geneticists are now creating “predictive algorithms” based on susceptibility genes for different diseases. And they’re able to map these gene variations faster than ever. In 1995, geneticists were identifying gene variations at a rate of 2 million per year; now, at UM alone, they’re up to 400 million per week.

For all this genetic information to be useful, though, a person must have his or her DNA “sequenced” — a very expensive proposition. In 2007, it cost $1 million. But two years later, it’s already down to $100,000. “What this means is there’s a big goal and a prize for the thousand-dollar genome, and it’s probably going to come in the next five years,” Vance predicted.  

Of course, there will always be folks who want to remain ignorant of susceptibility genes, but Vance and Goldschmidt expressed concern that doctors are among the worst offenders on this score. “One of our big challenges is that physicians have little genetic knowledge,” Vance observed. “We really have to change our medical school training.” Moreover, many doctors are averse to learning about genomics, fearing it could become another source of malpractice lawsuits. “When you are asked to start using information that you don’t understand, that you’re not trained to, that makes you even more nervous,” he said. Goldschmidt added that “a more foolproof system” will need to be developed to shield doctors who use genomic-based disease susceptibility tests from liability claims.

By Kirk Nielsen