Professor's Journey from Academia to Industry
Hearst is an Emeritus Professor of Chemistry and also Founding Director
and Vice President for New Science Opportunities at Cerus Corporation
in Concord. Discoveries in the course of his academic career at Berkeley
have led him to his second career in industry. Both careers, he says,
have been enormously gratifying. Born in Vienna in 1935, Hearst and his
family left there in 1938. I got into chemical engineering because
I was good at math, as was my father, who had been a banker in Vienna.
Back in those days, if you were good at math, you were encouraged to go
into engineering, Hearst said.
He accepted a scholarship to Yale and there met one of his mentors. Through a lucky chance, Jon Singer was my teacher for a physical chemistry course. Singer had taught at Caltech and encouraged me to go west after graduation, singing the praises of California. Now, I had never been further west than Pennsylvania at that point, but I went. Hearst said with a laugh.
At Caltech, I got to know Jerome Vinograd, an effective and wonderful human being and one of the pioneers of the molecular properties of mitochondrial DNA, Hearst continued. Vinograd invented the cesium chloride density gradient, an analytical and preparative procedure of such enormous value that he was a household name to all research scientists. He was a great mentor and taught me a great deal about interacting with students. One thing I would highly recommend to most people, whether they are in science or not, is to find a mentor who can play a professional role in their life, he said.
When Hearst joined the faculty in 1962, DNA was still an emerging molecule. It had only been a few years since Watson and Crick had discovered DNAs double helical nature, and the genetic code had yet to be established. My lab started out doing biophysical structure studies of DNA, looking at the elasticity of DNA and the physical processes of DNA transcription and replication. I attracted students who wanted to work on the cutting edge, Hearst recalled. And I loved being an educator. I got a lot of satisfaction working with and teaching students at Berkeley. Being a professor is one of the greatest jobs in the world.
In the mid 70s, psoralens were brought to Hearsts attention by Tom Cech, who was his graduate student at the time. This was a way to freeze dynamic processes in the cell, Hearst said. According to Hearst, psoralens are small molecules that wedge themselves between the two strands of DNA and then, when exposed to photons of UV light, form crosslinks that prevent DNA from replicating. Psoralens occur naturally in plants, including limes and celery, which use them to kill attacking insects and fungi.
The event that got the ball rolling in psoralen photochemistry and that led toward my eventual entrance into industry was the synthesis of the first positively charged psoralen, Hearst continued. We knew that psoralen fit into the DNA structure, because the drug was the right size to get close to the bases on both chains. However, it was thought that the bases in RNA were too far apart for crosslinking. As soon as we proved that we could crosslink RNA, we opened the door to killing RNA viruses, including HIV, with psoralens, he said. It was also exciting to show that we could block transcription and other DNA processes using psoralen, showing that the crosslinking effect was indeed working the way we thought it would.
Ramping up my work with psoralen, I started looking for a technician. Id heard about Stephen Isaacs, who was then selling handmade terrariums on Telegraph, and I convinced him to come work for me, Hearst said. It was obvious from the start that Steve had great hands and great people skills. Within six months of his joining the lab, we had synthesized AMT (aminomethyltrimethyl psoralen), the first positively charged psoralen, in collaboration with Henry Rapoport. The three of us decided to start a company, HRI (for Hearst, Rapoport and Isaacs) that was basically a garage-based company, around 1978. We supplied psoralen and radiolabeled-psoralen for research. In 1986, Steve finally left my lab to build up HRI, and he took four other students with him!
We were always coming up with new ideas after that, Hearst remembered. In 1989 he met Larry Corash, a hematologist at UCSF, who had heard about Hearsts work with psoralens and had the idea of using them to kill organisms in blood. Larry became a co-founder of Cerus, which got started through the funding of this idea by Sand Hill Partners in 1991. We had come up with a simple, practical way to kill pathogens in the blood. In 1992, Steve became the CEO of Cerus and has done quite well, a fact in which I take great pride, considering he was one of my students. I retired from full-time teaching and research at Berkeley in 1996 and have devoted myself since then to looking for new scientific ideas and projects that Cerus could develop, though I still remain active in the College, directing post-doctoral students, Hearst said.
Cerus makes products to increase the safety of blood. We can treat donated blood and kill most viruses or bacteria that are present, even if they cannot be detected or tested for, Hearst explained. This is because they contain DNA and RNA, whereas the three components of whole blood that are used in the medical fieldred blood cells, plasma and plateletsno longer utilize the small amount of nucleic acids they contain. Cerus exploits this fact because positively charged psoralen is attracted to the double-stranded nucleic acids. When the blood is then exposed to UV light, a photo-chemical reaction occurs that makes the crosslink permanent within the DNA and/or RNA of the potential contaminant. Then when the virus or bacteria tries to replicate its nucleic acid, the crosslinked DNA or RNA cannot be copied and the virus or bacteria will die, he said.
Now I work with scientists at different institutions that are testing Cerus products. I also look for emerging technologies and techniques that Cerus can either acquire or partner with. Im quite content working with the scientific ideas. Im in love with science, Hearst said. Currently Im looking at anti-cancer products. This came about through looking to make bone marrow transfusions safer.
Looking back over my career at this point, Im very proud
of the fact that I feel good about what I have done, said Hearst,
who cited the importance of friendships and loyalties in his achievements.
As an educator, Im proud of my students. I spent 35 years
as a chemistry professor and feel very privileged to have impacted so
many lives and facilitated so many careers through my teaching. Even
now, I can sit next to people on a plane and find out I taught them
freshman chemistry many years ago, he said. But I also feel
good about my contributions to scienceto psoralen chemistry, to
the mechanism of DNA repair, and to photosynthesis. I hope I will be
leaving something truly significant behind, a legacy to the human condition.
I would highly recommend to most people, whether they are in science or not, is to find a mentor who can play a professional role in their life
I got a lot of satisfaction working with and teaching students at Berkeley. Being a professor is one of the greatest jobs in the world.
Cerus makes products to increase the safety of blood