Peter Walter (UCSF, HHMI) : Harnessing Serendipity
– In Conversation With Claudia Dreifus, New York Times.
Peter Walter, a professor of biochemistry at the University of California, San Francisco, studies how proteins within cells communicate with one another. His contributions have been instrumental in shaping scientific understanding of how cells are organized and how they function.
While still a graduate student, Dr. Walter discovered the signal recognition particle, which guides proteins to their correct locations within cells. At U.C.S.F., his laboratory identified the inner workings of the unfolded protein response, which helps cells maintain properly configured proteins. Improperly folded proteins have been implicated in a variety of diseases, among them Alzheimer’s disease and cancer.
We spoke for two hours in February at his San Francisco home and more recently when he came to New York City to accept the Vilcek Prize, which honors the work of immigrant scientists and artists.
A condensed and edited version of the two conversations follows.
Q. Where did you grow up? Do I hear a Berliner accent?
A. Yes. I grew up in West Berlin during the Cold War years. My parents had a little chemists’ shop, which was like a second home to me. I think, in part, my scientific inclination was born in being around the fantastic materials there. That, and experimenting in the house.
It seemed natural for me to pick the chemistry track at university.
Unfortunately, the science instruction at the Free University of Berlin was, in the early 1970s, extremely proscribed. There was no room to discover the unknown, which to me is the essence of scientific inquiry. You were given protocols to follow. It was always clear what would happen at the end. You were graded on getting the expected outcome.
This did not engage me. What interested me more was something developing in America, a new field where people studied the chemistry of cells and how life worked. I tried to read all I could about this biochemistry. But I was hindered because most of the important papers were published in English.
So to improve my English, I did something audacious. I signed up as an exchange student at Vanderbilt University in Nashville.
What’s audacious about that?
Well, we Germans don’t tend to migrate — we stay pretty much in the place we come from. At 22, I’d never lived anywhere but Berlin. I told my mother I’d be back in nine months.
How did you like Nashville?
It was absolute culture shock — a very small town with a church on every corner. My host family, lovely people, believed that America had won the war in Vietnam.
The university, however — Vanderbilt was a revelation. At the laboratory of Professor Tom Harris, I was allowed to do real research. Here I was, this lowly exchange student, and I was given use of the most expensive equipment and complete freedom to design my own experiments.
At Vanderbilt, I began to appreciate something uniquely American: the possibility of personal reinvention.
And so, when one of the Vanderbilt trustees suggested I apply for my doctoral studies to Rockefeller University, where the students were free to design their own curriculum, I didn’t hesitate. And when I only made it to the Rockefeller wait list, I still hoped.
But then came some serendipitous luck: At the last moment, an accepted student opted for Harvard, and I was offered his place. So I told my mother that the nine months would be a little longer.
At Rockefeller, you ended up working in the laboratory of Gunter Blobel, who won the 1999 Nobel Prize in Medicine. What was he researching when you joined his group?
He was trying to understand how the protein machines inside the cells organized themselves, and how they knew where to go within the cells to perform their functions. Gunter’s idea was that, in nature, things don’t just happen. There’s a machinery inside the cell that’s important to its organization.
He proposed that the proteins had these chemical ZIP codes that directed them to their destinations. At the time, this was unproven, and many of Gunter’s rivals disparaged it.
I spent four years taking the process apart biochemically and discovered this signal recognition particle that directs the proteins to their correct location. This was an important step in proving the validity of Gunter’s ideas.
Few graduate students get to make such a significant discovery. Did the experience give you confidence?
I think it gave me the confidence to, in 1983, open my own lab shortly after graduate school. Once you realize you’re good at looking into the unknown, it no longer scares you. In my lab at the University of California, San Francisco, we took some of the research that Gunter pioneered further by studying the folded protein response of cells.
A cell is more than a bag of chemicals. It has a power plant, garbage disposal units, libraries, the genome, roads and traffic lanes. All the protein components produced have to fold up correctly within the cell. Proteins that are not properly folded can be toxic.
We discovered how cells determine if they have sufficient capacity to fold proteins into their appropriate three-dimensional shapes. Not having enough capacity to do this triggers the unfolded protein response.
Why is this important?
If cells can’t do it, they die. Thus, the unfolded protein response makes life-or-death decisions. It is connected to numerous human diseases like diabetes, neurodegeneration, cancer.
You had cancer six years ago. What did your time as a patient teach you about your lab work?
The treatment I got was pretty generic. It made me feel what an extreme dearth of knowledge we have about why cancer cells grow out of control and what we can do about it.
I am happy to say I’m disease free as I sit here. But I’ve had friends die because there was no treatment possible. So, we really need to understand what fundamentally goes wrong in these cells and how we can correct the defect. I think from that angle, yes, it gave my research a very strong new motivation.