Biodesign Institute studies customized prescription technology

Only a handful of the nation's medical schools now teach molecular science, but soon doctors without this education will be on the road to obsolescence. Scientists are looking deep into the genetic code to find an answer in the molecules to the riddles of disease diagnoses and treatment. Variations within the molecular structure of genes, called haplotypes, may explain why a drug helps one patient but triggers an adverse reaction in another. When fully understood, haplotypes will play a leading role in diagnosis as well as prescription.

Imagine a world where a simple blood test tells the pharmacist which antibiotic or cholesterol drug will fix you quicker, based on your unique genetic makeup, or "haplotype." Researchers at The Biodesign Institute at Arizona State University are developing processes to use haplotypes to improve the efficacy of prescription drugs — a solution that could be crucial to reducing the number of deadly adverse drug reactions.

Institute director George Poste told health-care policymakers attending the "Pathways to Change: Transforming American Healthcare in the Next Decade" symposium that "most contemporary medications work in 40 percent to 50 percent of patients." Some of the most highly effective drugs, he added, are also high-risk or even dangerous in terms of side effects to some of the population.

Plenty of adverse drug reactions occur each year. According to a landmark Institute of Medicine study, approximately 44,000 people die in American hospitals annually due to treatment errors, many of them drug-related. Some research indicates the number of preventable deaths could be as high as 98,000. So the Biodesign Institute's project aimed at haplotype-based drug prescription could save thousands of lives, as well as get us well, faster, with fewer side affects.

While legislators focus on prescription-drug safety and costs, and health care IT forges ahead with electronic prescribing technology, Poste wondered if now is the right time to pursue development of drugs custom-fit to patients. Poste — named "R&D Scientist of the Year" by R&D Magazine in 2004 — explained that the "core of empirical medicine, that one size Rx fits all," is fundamentally flawed.

"Disease is not uniform. Patients are not uniform," he continued.

"The symptoms may be the same but there is a difference, a difference of molecular pathology. Plus, we are genetically unique." Poste added that haplotypes, or genetic variations, must be considered during diagnoses, as well as in developing and prescribing drugs. Variations in an individual's genes can predispose toward or protect them from specific diseases or disease subtypes.

Haplotypes are the reason that African Americans have a higher rate of sickle-cell anemia, or Hopi and Navajo Native Americans exhibit higher than average frequency of diabetes — something Poste refers to as the basis for "ethno-pharmacology." But haplotypes distinguish people within ethnic groups as well as between them.

So where are we now in the haplotype-drug pursuit? Researchers know people vary genetically, and can be grouped according to their genetic variations; and doctors have identified disease sub-types. "What we really don't know is where the drugs fall" in the genetic categories, Poste explains. Sometimes, though, we luck out. Take BiDil, for example, an oral drug that enhances the patient's nitric oxide, used in treating heart failure. "It was found through testing, rather than through genetic mapping," that BiDil is exceptionally effective in treating African Americans suffering from heart disease, he said.

Or consider the well-known "miracle" cancer drug, Herceptin. If you are a woman with a variation of a gene known as HER2, you are predisposed to HER2 metastatic cancer, a subtype of breast cancer. Women with this haplotype whose cancer hasn't responded to other treatment usually respond amazingly well to Herceptin, generically known as "trastuzumab."

For the quality of health care to improve, medication and treatment must be approached differently — based on haplotype rather than diagnosis, Poste said. Ideally, someday we'll be able to "match the right drug to the right subtype of disease" for other conditions. Since doctors write approximately 3.1 billion prescriptions a year, the potential for improving health, saving lives and cutting costs is immense. Poste even sees mandated haplotype-based drug prescribing as a way of reducing malpractice lawsuits.

He's equally jazzed about "biosignatures," another institute research project. "Biosignatures map the molecules that are the footprints of disease," he explained, allowing doctors to predict which diseases or conditions each patient is likely to develop in the future. Biosignatures detect "pre-symptomatic" disease, allowing time to possibly prevent or mitigate illness.

Interestingly, biosignature technology began as a Department of Defense project in the late 1990s. The initial concept was to develop technology that would allow people to check their own health status at any time, anywhere, using a simple needle prick. For example, soldiers on a battlefield could monitor themselves daily to detect exposure to a deadly virus or other biological weapons. Researchers came up with the "doc-in-the-box" concept, a small, mobile lab that automatically analyzes the tested person's blood to detect pre-symptomatic changes.

Here's how they hope it will work: the patient sticks his or her finger into the box, encountering a pricking device that absorbs and tests the drop of blood fluid that results. The device assays hundreds of tests, reporting anything that has changed in the person's system compared to earlier tests.

Although initially viewed as a device for military and government use, researchers now think it could be used to predict diabetes, Alzheimer's disease, heart disease and other conditions. In a best-case scenario, there'd be a doc-in-the-box in every home, and we would be able to monitor our own health with fewer trips to the lab or hospital.

Advances in haplotypes and biosignatures will change health care, Poste said. Diagnostic medicine, long viewed as the less exciting area of medical practice, will grow substantially as a result of customizing medication based on molecular biology. Doctors will need to learn to diagnose and treat patients differently based on the improved technology. That's a problem, because today only 18 of 135 medical schools are teaching molecular science, Poste said — "which is a setup for failure."