"Beating the Odds"

Dr. Andrew Dahlem, Vice President of Toxicology, Drug Disposition and Pharmacokinetics at Eli Lilly and Company, knows that the road to drug discovery is a long one. "Because development cycles from discovery until a successful launch are greater than 10 years, a researcher might only have one or two or three opportunities to discover a new drug in their careers," says Dahlem, a 17-year research veteran. "The probability that these great ideas will turn into medicines is very low, and that's because there are so many factors that are involved in the discovery and development of that new medicine that may foil our attempts."

A pharmaceutical research company is in the business of creating a physical substance – a medicine – from a series of ideas, Dahlem says. For this process – both creative and scientific – to succeed, many complex factors must align. Drug discovery often is a combination of luck, inspiration, and long, hard work in the lab. In each company, teams of researchers dedicate themselves to finding the best disease targets for a new medicine, to looking at how that drug works in the body, and to determining whether it is safe to use. Even so, surprises are more the rule than the exception, and many promising drugs have had to be left to gather dust on the shelf because they did not perform as expected.

Dahlem believes that genomics is key to creating a more predictable stream of medicines in the future: "We're standing at a threshold in understanding the human genome," he says. "We're able to actually look into the code...and understand how genes relate to disease, and we're unlocking that code step-by-step. For young scientists getting into this business, fields like proteomics and genomics are vast frontiers of unexplored territory in science that are going to have an outcome that involves changing life's existence for humans and altering diseases."

The implications of personalized medicine are far-reaching for drug development, he says, allowing researchers to take a closer look at various safety issues in different patient populations during clinical trials. "The way that drugs, at least in recent history, have traditionally been developed in the pharmaceutical industry is that we develop medicines for a population of people, and in that population, the medicine can have different effects in different people." The decision to move ahead with a medicine and, ultimately, the Food and Drug Administration's decision on whether to approve it, will depend on the balance of those better-defined risks and benefits.

Most importantly, personalized medicine could make drug development more predictable by helping identify patients who respond best to a specific treatment. "What we talk about with individualized medicine is not a population or a community of people in treating their disease," Dahlem says. "We talk about the right drug for the right patient at the right time."

Of course, Dahlem sees challenges in implementing personalized medicine. "I worry about some changes that are taking place in our industry that may inhibit our ability to test the right drug or to give the right drug to the right patient," he says. Personalized medicine is based on the premise that we administer medicine based on a deeper understanding of the disease and the individual, so traditional healthcare mechanisms such as formularies would need to adapt.

The challenges of drug discovery have not dissuaded Dahlem from his mission. "The single greatest motivation to work in the pharmaceutical industry is the knowledge that there are patients who are waiting for the medicines that we are making, who need the therapies that we can create for them," he said. His motivation is anything but abstract. In fact, it is deeply personal. As a child, Dahlem developed a case of rheumatic fever after a bout of strep throat. "It had an effect on my heart and, as a child in third grade, I was unable to play with other children," he said. "In fact, I had to lie in a bed for months and be carried. It was a medicine that I took that allowed me to get up again, and it was a medicine made by the company that I now work for. That's why I joined the pharmaceutical industry."

There are two ways to beat the odds in the discovery of new drugs: strong data and a good dose of passion. Genomic data will help transform the unpredictable into the predictable, and passion will help researchers endure the long path to the next breakthrough drug. "To work against the odds for the good of the people who need the medicine," says Dahlem, "that's what makes the difference."

This article is based on a personal interview with Dr. Dahlem.