You are here

Meet the Scientist – and Former Smoker – Behind a Pfizer Smoking Cessation Medicine

Jotham Coe knows all too well about the powerful grip of tobacco addiction. Growing up in Belmont, Mass., his mom and dad smoked, so did his older sister, aunts, uncles, and grandparents. At 16, Coe picked up smoking, and after several quit attempts in his 20s he finally succeeded at the age of 25 from 2+ packs a day. His dad, also a two-pack-a-day smoker, unfortunately was unable to quit. Suffering from emphysema, he spent his last decade of life struggling to breathe. He died at the age of 69, four months before Coe's twin sons were born.

"My family's story is not uncommon, sadly," said Coe. "What some don't realize is that the pain and suffering doesn't happen one day, it happens gradually and is unstoppable. It is extremely difficult for most to quit smoking."

While he was unable to help his father, Coe, who has a Ph.D. in organic chemistry from MIT, went on to help develop a medication to aid smokers in quitting smoking.

Taking on Nicotine Addiction

Times have changed since Coe's youth in the ‘60s and ‘70s when smoking was commonplace. Today, smoking rates have dipped to an all-time low in the U.S., from 21 percent of the population in 2005 to 15 percent in 2015. 1Still, smoking remains the leading cause of preventable death in the country: more than 480,000 people die per year due to smoking-related illness. 1Smokers, on average, die a decade earlier than non-smokers and are at higher risk for developing a long list of ailments, including coronary heart disease, stroke, and lung cancer. 2Indeed, half of all smokers will die of smoking-related illness.3

While the medical establishment had been speaking out about the dangers of smoking since the 1950s, it wasn't until the late 70s that health officials began to recognize smoking as an addictive behavior. 4In a landmark Surgeon General's Report in 1988, the nation's highest health officer warned that smoking was not simply a bad habit, but a powerful addiction that alters the brain's structure and requires public health attention.5

When you smoke, nicotine travels swiftly to the brain, binding with receptors that release the feel-good chemical dopamine. As you continue to smoke, your brain gets used to the spikes in dopamine from smoking. When nicotine levels plummet, the brain experiences powerful withdrawal symptoms, making you crave another cigarette. This is how smokers become hooked.

Persistence, Patience, and Discovery

In 1995, Coe joined the team of Pfizer scientists who were working to find a new medicine to help people quit smoking. The team ultimately focused on the activity of a plant-based alkaloid found in certain flowering trees and shrubs which they believed could bind to the brain's nicotine receptors. Coe's initial task was to reproduce a synthetic form of this plant-based chemical. The research team spent two years testing variations of the compounds, but none produced the desired effect on the nicotine receptors.

"Molecular Carpentry"

Coe likens his work as a chemist to "molecular carpentry." He tinkers with complex molecular structures aiming to produce a desired effect. In 1996, Coe had a "eureka" moment. He had previously done work with morphine chemistry and realized its ring structure was very similar to the plant-based alkaloid they were studying. Diving into morphine research papers, he discovered that moving the location of a single nitrogen atom likely caused it to behave like nicotine. He wondered if the same could be done with their new molecule.

His hunch was right, and soon the team had a series of compounds to test. In total, it took five years and a large team, but their efforts bore fruit: they had invented a new molecule that could be further developed into a smoking cessation treatment. It would take many more years of development before a medicine reached the market.

"Working to discover new medicines is really challenging and requires persistence, patience and stick-to-itiveness," said Coe. "Inventing one that actually made it is a major accomplishment."

Helping Others

Coe sometimes wonders about his father. He died in 1998, the year the new compound went into development. If there were more treatment options available to help him quit smoking decades earlier, maybe he wouldn't have suffered from emphysema. (His mom quit in her 50s and is 86 today.) But since working on this smoking cessation medicine, Coe has met many people who've said it's helped them or family and friends quit. "That's always a gratifying thing to hear," said Coe.

While the victories are rewarding, Coe continues in the lab in the long march for new medicines that can help people. "I've spent the past 28 years trying to find other medicines. That's what we do."

2Schroeder SA. Smoking cessation should be an integral part of serious mental illness treatment. World Psychiatry. 2016;15(2):175-176.
5Benowitz NL. Nicotine addiction. N Engl J Med. 2010 Jun 17; 362(24): 2295–2303.