(Below is an opinion piece by our own Jonathan Dordick on the need for personalized medicine. Dordick is the Howard P. Isermann Professor of Chemical and Biological Engineering and Director of our Center for Biotechnology and Interdisciplinary Studies. This winter he spoke at World Economic Forum in Davos about pharmaceutical safety and development. He shares some of those thoughts and others here with us at The Approach.)
“Drowsiness.” “Hallucination.” “Thoughts of Suicide.”
Anyone who picks up a magazine or watches primetime TV is woefully aware of these and myriad other potential side effects from a new prescription drug. Drugs cause side effects for a variety of reasons, and most of them are based on our individual biology. A drug that barely touches one man’s rheumatoid arthritis gives another woman near-complete relief. An asthma medication might allow one child to play soccer without asthma attacks but dangerously worsens the asthma of another child. With medicine, it is the personal that matters – it is the personal that could spell the difference between a cure and potentially deadly side effects. Medicine must move away from the impersonal to the personal.
With the massive progress made in science and medicine, including great reductions in genetic testing costs, an era of personalized medicine could be at hand. As scientists, we already know a great deal about the genetic makeup of some patients. For example, we know that some people metabolize drugs much faster or slower, making the average dose of certain medications either far too potent or near ineffective for some patients. The first step toward personalized medicine is already used to great effect in the treatment of cancers. Today, tumor biopsies from individual patients are used to determine the optimal type of chemotherapy for their specific type of cancer. Over the next decade, our scientific knowledge base will likely be sufficient to transition to an era of medicine where the majority of our medical treatment is specifically tailored to us as individuals.
But, personalized medicine faces more than scientific barriers. To develop truly personalized medicine, the economic and regulatory issues may be more complex than the actual scientific drug discovery process. The process of drug discovery and the way new pharmaceuticals are regulated must be reinvented to allow for personalized medicine.
Differences between individual patients, at the most fundamental level of human biology, must be integrated into the drug discovery and development process. While this has been a goal of modern drug discovery, it does not fit the current blockbuster model of the pharmaceutical industry. It is really just simple math. The way the pharmaceutical industry is currently set up, the only way to recoup the exorbitant costs of drug development is to create a drug formulation that a large percentage of the population can take. If a drug supports only a small fraction of that population, the pharmaceutical companies cannot afford to bring the drug to market. To overcome this huge barrier to entry for smaller batch drugs, the cost of drug development needs to be significantly reduced.
Today’s complex drug approval and clinical trial process represents the largest portion of a drug’s cost to consumers. To reduce costs and better target drugs to the individual, preclinical studies for new drugs need to move away, at least in most cases, from using animals to test the safety and efficacy of new drugs. If two human beings differ significantly in a drug’s efficacy, than how can scientists legitimately discover drugs when preclinical data is obtained from something as biologically dissimilar from us as a rat or a dog? In my lab and others around the world, scientists and engineers are developing entirely new technologies that test the toxicity and effectiveness of new drug molecules using individual human cell cultures rather than live lab rats and other animals. In other words, it is possible that with such tools doctors could one day use your own cells to test the efficacy of a drug on your specific body. Such tools need to be integrated into the overall drug approval process, replacing the majority of the now-required preclinical animal testing procedures. While animal tests might still be required prior to clinical trials, such animal studies would be focused and small. This would ultimately save significant amounts of money in the development process and weed out unsafe drugs earlier in the approval process. Money would no longer be lost moving unsafe drugs through the approval pipeline only to scrap them at the start of human trials.
Regulatory hurdles also complicate the pathway toward personalized medicine. Today, a drug passes the approval process when the majority of patients in clinical trials taking the drug have relief of symptoms and limited side effects. The very notion of “personal” means that many of these current policies policing drug efficacy and safety would be outdated. We would no longer be concerned about the majority of patients, but the minority of patients. Regulatory hurdles must be tailored to realistic levels that weigh the risks and benefits of new drugs to the individual patient. This would require much more focused clinical trials instead of the traditional multiphase trial structure. Such trials would also be smaller and less costly than current ones.
Such a paradigm shift will be difficult, but would reshape drug discovery and transform human health care. Let us all make this fight personal.