Me-Too Medicine – 'Personal Genomics' Promises Drugs And Diets Tailored To Each Individual

Sausage or Fresh Fruit? It May Not Matter at All to Your Genes

By SHARON BEGLEY | Staff Reporter of THE WALL STREET JOURNAL – 8/23/02

The research of Jose Ordovas is driven by a simple observation: Only some of us take prescription drugs; everyone eats.

Research in “pharmacogenomics” has shown that the reason the same drug helps some patients, has no effect on others and kills an unlucky few reflects not blind chance but individual genetic differences.

Variations in cytochrome P450 genes, for instance, determine whether or not you make the enzyme that breaks down selective serotonin reuptake inhibitors, also know as SSRIs, like Prozac and dozens of other drugs, and so whether a standard dose will harm you. Tiny variations in the beta 2AR gene determine how asthma patients respond to albuterol. And Genaissance Pharmaceuticals of New Haven, Conn., recently discovered 29 genetic variations that affect how you respond to cholesterol-busting statins.

If DNA variations shape how we respond to drugs, reasoned Dr. Ordovas, director of nutrition and genomics at USDA’s Human Nutrition Research Center, Tufts University, Boston, shouldn’t they affect how we respond to food?

Circumstantial evidence says so. One person goes on a low-fat/low-cholesterol diet and sees levels of LDL, or “bad cholesterol,” plunge. Another substitutes trout for T-bone until he swims and still doesn’t see his cholesterol budge. One person can live on marbled beef and butter with no ill effects. Another gets a coronary.

This month, researchers led by biochemist James Ntambi of the University of Wisconsin in Madison report that mice lacking a gene called SCD-1 can eat all the rich, fatty foods they want and never become obese or diabetic. Humans have SCD-1 equivalents, raising the intriguing possibility that absence of these genes explains the lucky few who reach the age of 90 despite living on Big Macs.

The study of how food interacts with genes is called nutrigenomics. Although barely out of the starting gate, it is already explaining some puzzles. For instance, a gene called Apo E comes in three common varieties, or alleles. Apo E4 is associated with a higher risk of cardiovascular disease. But if an Apo E4 person eats a heart-healthy diet (fewer than 30% of calories from fat, fewer than 300 mg of cholesterol a day), he gets much more benefit than do other genotypes, and so faces virtually no increased risk of heart disease despite the “bad” gene.

“Environment is the leverage you have over your genes,” says geneticist Frederic Abramson. “What you can change most easily in your environment is what you eat.”

Only when an Apo E4 person meets a high-fat diet does trouble brew. His lipid and cholesterol levels soar, much more than Apo E2s or 3s do on an identical diet. Those lucky slobs can pack in buttered muffins with near impunity. But things even out: The lipid and cholesterol levels of Apo E2s and 3s respond less to a heart-healthy diet. And if you have mutations in the Apo A4 gene, those levels don’t respond at all to a healthy diet. All that broccoli for nothing.

A drink or two a day also seems to reduce the risk of heart disease, but this one-size-fits-all advice is genomically naive, too. Alcohol dials down cholesterol levels in Apo E2s, but increases it in Apo E4s. Similarly, exercise increases HDL, or “good cholesterol,” in Apo E4s, but has little effect on HDL in 2s and 3s. Still choking on oat bran? It can lower serum cholesterol only in Apo E3s, notes Artemis Simopoulos, president of the Center for Genetics, Nutrition, and Health in Washington. The rest of us needn’t bother.

Also genomically naive is the advice to limit sodium. Only 15% of the population has sodium-sensitive hypertension; for everyone else, cutting sodium has almost no effect on high blood pressure, says Gerald Combs, director of the USDA’s Human Nutrition Research Center in Grand Forks, N.D.

A final example. Women are told to load up on calcium for bone health. But the gene for the Vitamin D receptor has multiple alleles. “Some of the forms this receptor takes don’t respond as well to increased calcium,” says Dr. Simopoulos. With nutrigenomics, she says, “we’ll be able to target dietary advice based on your genome, rather than make general rules that fail for so many people.”

Dr. Abramson founded AlphaGenics in 1999 on that premise. For about $1,000, the Washington, D.C., company plans to offer genetic profiles, based on about 300 genes that predict how an individual will respond to a particular diet.

Standard medical testing is a long way off. But if a pilot test goes well this fall, AlphaGenics hopes to tell you whether choosing oatmeal over sausage will actually make a difference to your health.

E-mail me at sciencejournal@wsj.com.

DNA News Resource:  http://online.wsj.com/article/SB1030049228936780155.html?mod=googlewsj

DNA Nutritional Breakthrough:  http://www.dnaguidedwellnessproducts.com

A Double Helix With Mars Rising

Kristen Philipkoski 05.23.01  WIRED

SAN FRANCISCO — Hey baby, what’s your genotype?

It could happen. Each of us has a “genotype” and a “phenotype.”

Actually we have several. Genotype simply means our genetic makeup. Phenotype is the physical manifestation of genes, behavior and environment.

Don’t worry if these words mean nothing to you now. In the next 20 years, researchers believe consumers will become increasingly familiar with their types.

Researchers gathered Monday at the Biotech & Infotech Summit to describe how they think genotyping and phenotyping will affect consumers and drug discovery.

Before we can actually understand our own types, biotech and drug companies are trying to sort it out. By analyzing genotypes and phenotypes in large populations, researchers hope to makes drugs safer and more effective. They basically hope to give the right drugs to the right people.

Although researchers know that genes alone don’t dictate all disease and behavior, genes are a good place to start looking for red flags in post-Human Genome Project times.

Finding individual genes or gene variations responsible for disease is easier than figuring out what combination of genes, environment and behavior made you the way you are.

DNA Sciences, for example, has initiated a large genotyping effort. They began a project they call the GeneTrust in August 2000 to collect the DNA of anyone who would agree to donate.

Dr. Hugh Reinhoff, chairman and CEO of DNA Sciences, said he believes that identifying susceptibilities in individuals according to their genes will be a boon for consumers as well as business.

By recruiting people through their website, company researchers are taking genetic samples and grouping them appropriately for clinical trials.

If researchers have data showing that people with a particular genotype react poorly to the drug they’re testing, they can exclude those individuals from their study.

The drug would then get through trials faster and cheaper. And when it got to market, people who know their genotypes would have a better idea which drugs will work for them.

But Gordon Ringold, chairman and CEO of SurroMed, believes there will soon be a “revolution in phenotyping.”

Soon, researchers will need to ask not only what genes did you inherit, but what did you do and what did your environment do to put you in the state you’re in?

The company has proprietary technologies that Ringold said can quickly examine thousands of parameters in biological samples. The researchers then associate these characteristics with the physiological states of patients participating in clinical trials.

Like DNA Sciences, SurroMed hopes to make clinical trials faster and more accurate.

Dr. Charles Wilson offered a completely new term: “nutrigenomics.”

He might have seemed like a misfit, trying to fit in with the hip DNA crowd — if you didn’t know he was a world-renowned neurosurgeon, who invented a breakthrough brain surgery done through the nasal passages with no incisions necessary. He has performed over 3,000 of the surgeries. He is also director of the Institute for the Future, a think tank in Menlo Park, California.

What is nutrigenomics? It’s a way to design what you eat to match your genes.

“It’s just another ‘omics,’” Wilson said.

But he proposes it as a simple way to eat according to your genotype or phenotype. For example, certain foods, such as oatmeal, have been shown to be good for you if you’re at risk for heart disease.

As more phenotype and genotype information comes to light, so will the associations with what foods you should eat.

Obvious privacy concerns arise with collecting and disseminating genotypes and phenotypes.

Reinhoff showed a slide of the various protections that the company has put in place: DNA samples are kept in a locked and alarmed room with a video camera and motion detector that undergoes regular security checks.

Electronic information is stored on separate servers, distributed via a one-way drop from the Internet, immediately anonymized, password protected and encrypted.

The company’s “guiding principles” even say company officials will “work for laws that protect individuals from discriminatory, inappropriate, or unfair use of information about their genetic makeup.”

But privacy remains a worry, with no such laws yet in place in the United States and cases of abuse of genetic information recently reported.

DNA News Resource:  http://www.wired.com/medtech/health/news/2001/05/44009?currentPage=all

DNA Nutritional Breakthrough:  http://www.dnaguidedwellnessproducts.com