In Search of Immortality

Science is built brick by brick. Each result adds incrementally to our body of knowledge, and the walls steadily rise. It’s a process that has advanced science for centuries.

But that kind of methodical progress has never satisfied Vishva Dixit.

“I always wanted to discover something fundamental – to reach a level of immortality. Because, if you discover something fundamental, it’s going to last as long as mankind lasts. And if you discover something that’s fundamental and it helps people – that’s even more important.”

Vishva came to this conclusion in the 4th grade, after reading a series of Time Life books on science, and even he admits this was rather profound for a 10 year-old.

Revered by Warriors

Vishva was born in a small village in Kenya, a few miles from the equator. His parents were doctors, and his early life revolved around their work. They made house calls, mostly visiting local Kalenjin and Maasai cattle herders.

As Vishva observed his parents, what struck him most was the respect the fierce Maasai warriors had for them because they were doctors. His parents, on the other hand, were mostly worried about him witnessing the grueling day-to-day of practicing rural medicine. They tried to distract him, which is why they bought him the Time Life books. But Vishva followed in their footsteps, completing medical school and practicing medicine in the same rural communities.

“I was practicing medicine on a budget of $1 per person per day for people that were in exceedingly dire straits. Patients would be two to a bed, with another one between each bed, so we would be jumping from mattress to mattress.”

Vishva derived great satisfaction from helping people in such dire conditions, yet at times medicine felt too formulaic, leaving little room for experimentation.

“I kept thinking back to those Time Life science stories. I knew what I was doing was important, but I also knew I wouldn’t be discovering something fundamental performing the same procedures over and over,” says Vishva. “I wanted to make a lasting scientific mark and it just wasn’t possible there.”

So he left Kenya determined to have an impact on the scientific community.

Life and Death

Vishva joined a lab in the biochemistry department at Washington University in St. Louis, where he knew very little about what was going on around him. He’d never held a pipette or used a pH meter. He remembers being transfixed by the hypnotic spinning of the magnetic stir bars. Luckily, his mentor and professor, William Frazier, saw Vishva’s potential.

“It was an incredible apprenticeship. He taught me at the bench. We poured gels. We analyzed data together. We wrote papers together. Very few professors would have taken that kind of time.”

Vishva learned and excelled under the tutelage of Dr. Frazier for four years before he accepted a position as an Assistant Professor of Pathology at the University of Michigan in Ann Arbor. While there, he became fascinated by the idea of why cells die. How is the decision made? What is the consequence of those decisions? What if you have too little or too much cell death?

Slowly, Vishva and his lab began to uncover the biochemical basis for a form of programmed cell death. What they found was that cellular suicide occurs following the activation of small proteins called caspases by death receptors on the cell surface. Through a series of experiments, Vishva’s lab uncovered the key proteins in this pathway and identified a completely new biochemical mechanism for how they worked together to destroy a cell from the inside.

This type of cell death, called apoptosis, is calculated and deliberate. Different biological stresses can cause cells to activate the pathway for the greater good of the organism. Vishva and his lab were the first to define how our cells orchestrate this process, and today their work can be found in nearly every biochemistry textbook. Ironically, making fundamental insights about death sealed his scientific immortality.

“In many ways, humans as organisms live because our cells die. It’s hard to fathom, but in each of us some 300 million cells die every single minute. Through programmed cell death, cells that need to die afford healthy cells the ability to survive.”

New Foundations

Vishva’s work laid the foundation for an entirely new field of research and has even fueled drug discovery efforts targeting programmed cell death. Though it was a significant discovery, Vishva wasn’t satisfied. He wanted to learn more. That desire compelled him to join Genentech in 1997 as the Director of Molecular Oncology.

“I could have my cake and eat it too,” says Vishva. “I could continue to do the basic research that I loved, but I also had the opportunity to be involved in drug development.”

What Vishva found most surprising about working at Genentech was just how different it was from his original conception of a biotech company.

“It’s a unique place – a true science and data-driven organization, which is rare in this space. But I’m also still struck by the sincerity of the organization and its people. It’s a decision I’ve never regretted”

Today, as a Vice President and Senior Fellow in Early Discovery Research, Vishva heads Genentech’s postdoctoral program while continuing his lab research on mechanisms of cellular death in the context of inflammation.Understanding this connection could build a better basic science framework to conceptualize inflammatory diseases like rheumatoid arthritis or lupus.

“Our larger goal is to discover what drives certain types of inflammation, and our bet is on cellular death. Dying cells are very inflammatory and it could be the fuel to a cycle of inflammation.”

In Vishva’s mind, there isn’t a better place to do this kind of work.

“People sometimes ask me what it’s like to work in industry, and I’ve always said to them, ‘I don’t have the foggiest idea. Because I work at Genentech.’”

Vishva Dixit is a Vice President and Senior Fellow in Early Discovery Research at Genentech. Learn more about his work here.