Sometimes it only takes one inspiring educator to set you on your career path. As an undergrad at UC Davis in the late 1970s, Jon Cook had a charismatic professor who sparked his interest in the field of toxicology, which studies the safety effects of drugs and chemicals on living organisms.
“This guy was huge; he was 6 feet, 6 inches tall and 300 pounds and played football in college. He was so jovial and had so much enthusiasm,” says Cook, Chief Toxicology Scientist at Pfizer’s Groton, Connecticut research site.
As part of their course work, they did field research with California’s migrant farm workers to study the safety effects of spraying pesticides. In fact, the professor’s research eventually led to important safety regulations enacted around pesticide exposure. “He improved health and safety in their workplace, and that just seemed so practical and helpful because the migrant laborers had been working in really bad conditions,” he says.
Cook went on to earn a Ph.D. in toxicology and embark on 30-year career in the field, primarily working in the pharmaceutical industry. As a toxicologist, Cook primarily sees his role as a problem solver, helping to understand the human relevance of safety issues that would otherwise hold up a drug development program. “I have a history of addressing problems, when we have adverse findings with safety,” says Cook.
In a recent conversation with Cook, he shares some insights into the discipline that covers biology, chemistry and public health and its role in helping ensure that medicines are safe.
Get Science: When do toxicology studies occur in the process of developing a new medicine?
Cook: Toxicologists are actually working throughout the drug discovery process, from the first selection of a target to Phase III. In the preclinical phase, the biggest part of drug safety is just to make sure we’re designing a safe molecule, and later it becomes more about understanding biomarkers and what are the risks for patients. When you get to the clinical trial phase, I think of us as an “enabler,” and we’re not the primary focus. We’re there to help ensure a medicine is safely moving along the approval pathway. When it eventually becomes a drug, the safety aspects are added to the label to guide physicians.
Get Science: What are some of the main safety issues with medicines that toxicologists study?
Cook: In the very beginning we look at whether a molecule would be genotoxic, destructive to a cell’s DNA and do rodent/non-rodent safety studies. We have to demonstrate safety in these areas before we can conduct clinical trials in humans. The other most important piece we look at is whether a drug could cause birth defects during embryo-fetal development.
Get Science: How has the field of toxicology evolved in recent years? Toxicologists are playing a much more active role in helping bring good science to lawmakers to enact legislation that protects human health.
Toxicologists are playing a much more active role in helping bring good science to lawmakers to enact legislation that protects human health.
Cook: If you’re talking about the whole field and not just drug development, we’re trying to play a much more active role in providing good science to lawmakers to enact legislation that protects human health. Also, toxicology as a field is working on ways to reduce animal studies and instead use to in-vitro systems that use advanced cellular models.
Get Science: Are there any new technological advances that are transforming toxicology in pharma?
Cook: The biggest transformation has been the use of 3D cell culture systems,which more closely mimic organ system, to help us predict adverse outcomes, leading to better translation and lower drug failure rates. That’s probably the biggest piece that is moving the field forward. To give you one example, if you take a liver cell, and do a primary culture — growing cells within controlled conditions — within three days it loses most of its normal metabolism capabilities. But with these advanced 3D culture systems, they can change the physiology of liver cells so they maintain normal levels of drug metabolizing enzymes and therefore respond to a drug more similar to what it’s like in realistic conditions in humans.
Get Science: What excites you most about being a scientist today working in pharma?
Cook: The thought of being able to advance important medicine to help treat diseases, especially cancer. I have worked in oncology my whole life, and it used to be that we really weren’t able to cure people. Now if you look at oncology, with precision medicine approaches, we’re able to identify whether patients will respond to our drug and produce meaningful increases in people’s life expectancy and in some cases to cure them. But the growing field of immuno-oncology brings up issues of how we do safety, and apply precision medicine approaches to toxicology and safety too. I never thought we would be there and we're almost at a turning point in medicine. It just about gives you chills down your back.