A Miracle of the Right Medicine

Although the term pharmacogenetics was coined in 1959 by the German human geneticist Friedrich Vogel, researchers and health practitioners had long known that different people react differently to similar treatments and that the connection was often inherited. Just as our different genotypes give us, for example, different eye colours, our genes can make us more or less tolerant, sometimes even resistant, to different drugs and dosages.

Scientists began sequencing genes in the early 1970s, but when the Human Genome Project completed sequencing the entire human genome in 2003, an effort that had started in 1990, the full potential of genetics to reshape human lives came into view. As the process of sequencing genes has gotten faster and cheaper, healthcare providers and tech companies have been using genetic testing to improve an array of health outcomes. One well-known application, for example, is undergoing a genetic test to learn about a condition that runs in the family before symptoms present themselves. But pharmacogenetics is not about diagnosis or predicting health conditions. Instead, it’s an analysis of how genetic factors contribute to the metabolism, response and adverse effects of a given medication. While pharmacogenetics can bring down healthcare costs, decrease suffering and help patients get back to work and their life responsibilities more quickly, the field still has limitations — and much-unlocked potential.

“I can do sequences in my lab that are 10 times more expansive than what the Human Genome Project achieved. Instead of looking for a million variants, I can look at 10 million variants in about eight hours, versus 13 years. And I can do it with a technician operating the equipment. So I can get genetic data for about $100 versus the $2.7 billion the Human Genome Project cost,” says Bruce Carleton, an associate member of the Department of Medical Genetics at the University of British Columbia. 

Studies from around the world have found relationships between certain drugs and certain DNA profiles. Depending on the quality of the studies, some of the correlations are stronger, some weaker, says Carleton. One of the best-known examples is codeine, which is one of the three ingredients of Tylenol 3. People with certain genes are able to effectively metabolize codeine so that it becomes morphine in the body, providing pain relief and, in some cases, increasing the risk of adverse effects. But individuals who have two inactive copies of the CYP2D6 gene are poor metabolizers and may so experience little or no relief.

Two main bodies worldwide share research and create guidelines for patient care: the Dutch Pharmacogenetics Working Group, which holds more sway in Europe, and the Clinical Pharmacogenetics Implementation Consortium, which is used more in the United States and the rest of the world. The U.S. Food and Drug Administration, which has its own research process, also issues recommendations and now requires new drugs coming to market in the U.S. to undergo pharmacogenetic analysis.

Chad Bousman, an associate professor specializing in mental health in the Department of Medical Genetics at the University of Calgary, says there are currently widely accepted guidelines for 88 drugs and 25 genes. The FDA currently lists 62 gene/drug associations strong enough to merit guidelines; 22 of those are associated with safety concerns — that is, there could be potentially adverse, even fatal effects, for patients with certain genetic profiles. The FDA lists another 40 gene/drug associations which have weaker associations. 

Most pharmacogenetic associations apply to three key fields of medicine — psychiatry, oncology and cardiology. The benefits to the patient and to healthcare payers differ from field to field. In psychiatry, pharmacogenetics can help a doctor rule out drugs that would be less effective, reducing the amount of time — and the frustration of repeated trial and error — needed to get a patient back to work and other duties; it is often applicable in cases of short-term disability. In cancer treatment, it can help healthcare providers avoid treatments that are too toxic for some patients and give more effective doses. In cardiology, it can prevent hospitalization due to adverse effects, as well as discourage healthcare providers from prescribing medication that may have little or no effect on preventing heart attack and stroke.

“A good example in terms of the value of pharmacogenetics would be clopidogrel or Plavix, which is a blood thinner activated by a gene that some people don’t have a functional copy of,” says Carleton. “So you could be getting a blood thinner to prevent heart attack and stroke and it may not be working for you.”

Though more insurers are covering pharmacogenetic testing, it’s much more common in the United States than in Canada, says Carleton. There are many arguments about the most cost-effective time to test. Testing healthy infants — that is, testing well before someone needs any sort of treatment — could ensure that the information is available before each prescription is written, and so avoid adverse effects and wasted treatments over a lifetime, says Bousman. But that raises issues of privacy and how that data will be managed and analyzed over decades. Meanwhile, testing on diagnosis can prevent potential adverse effects and shorten the treatment process, while testing after or during the course of treatment allows treatment to start immediately and targets those who are most likely to benefit. Within the field, there’s also been the question of whether to test specific genes related to the case at hand or do full-panel testing off all the associations.

“A decade ago, it would have been a harder sell to just test everything because it did cost more for every gene you added,” says Bousman. “These days it’s just becoming so incredibly cheap that there’s little difference between testing one gene or the full panel. Doing it separately means you’re paying every time.”

Both Carleton and Bousman point out that, especially in the U.S., there has been a boom in labs offering pharmacogenetic testing, some of them overpromising associations based on weaker research. 

“Reimbursement [for testing] is available from payers in the U.S., but there’s no standardization regulation at the laboratory level of who can do it, how to interpret it, how the results are presented to the physician,” says Bousman. “So it’s become a bit of a Wild West there.”

Yet an increasing body of research, improving technology and smarter public policy suggest that pharmacogenetics will become increasingly important to patients, healthcare providers and payers over the next few years. More understanding of exactly what ties certain reactions to certain genetic profiles will allow pharmaceutical companies to produce medication that’s more customized.

“There are very, very few good drugs or bad drugs, but there are lots of right drugs and wrong drugs for individual patients,” says Carleton. “Right now we’re predicting response. That’s one thing. Understanding the biology that underlies the response is another. When you understand that biology, you can begin to do something about that by redesigning drugs or creating ways to block certain pathways that are problematic. It’s changing very fast.”