Gerald Pao's eclectic life has brought him from the fashion runways of Europe to the labs of the Salk Institute.
The senior research associate in Inder Verma's Laboratory of Genetics is of Chinese and Caucasian descent, but was born in Spain, where his father was a diplomat and also worked with the counterintelligence agency. He spent his childhood and teenage years in Madrid and experienced everything from modeling for the United Colors of Benetton to fighting off schoolyard bullies. He discovered a love for science in first grade. Along the way, he became fluent in five different languages.
These experiences shaped his future as an accomplished scientist. Pao dedicated nearly ten years of his life to one study and recently published his findings in the journal Nature. The results? A dramatic discovery with the BRCA1 gene that could pave the way to detecting breast and ovarian cancers earlier in patients.
Your childhood is like something out of a movie. How does a Chinese boy born in Spain learn how to speak five different languages fluently?
My parents originally came from two different regions of China, and my mother spoke Cantonese and my father Mandarin. To understand each other, they spoke English until my mother learned Mandarin. They both spoke Spanish, as we were living in Spain, but they wanted to preserve the ancestral languages, so they refused to let us speak Spanish at home. For my siblings and me, schooling was completely done in German from kindergarten to 12th grade. Our parents sent us to German school because they believed it was a better educational system, less focused on memorization and with a greater emphasis on causal analysis, compared to Spanish schools.
Some people may think growing up in Madrid sounds exotic and fun, but what was it really like for you?
It was definitely difficult without any Asians around, mostly because racism at that time was so ingrained in society, people did not even know they were discriminatory when they were. I had accepted the xenophobic behavior of many Spanish people as a fact of life and thought it to be the normal baseline. I did not realize it was a discriminatory behavior until I came to San Diego for college at UCSD and experienced the difference of living in a truly multicultural society that aims at integration.
Your father did some work in military counterintelligence. Did you ever see him bring his work home? Anything similar to a Jason Bourne movie?
On two occasions we met up with the CIA station chief in Madrid and his wife in a Chinese restaurant that a friend of my father owned. They exchanged information on individuals, showing each other pictures of people they were tracking. On another occasion I remember going with my father to some diplomatic function. He was pointing out that almost every military attaché was indeed a spy. From what I saw, the real-life version had nothing of the excitement of the Bourne movies.
What motivated you to go into science, and when did you realize that you wanted to become a researcher?
My father wanted me to become an architect, but I had no desire to pursue anything that I considered "artificial" in the sense that it was man-made as opposed to naturally occurring objects in nature. My interest was first in animals throughout kindergarten and into first grade. While in second grade, I studied a subject called Sachkunde, which is an amalgamation of natural science that literally means "the study of things." From then on, my interest was broadened from zoology to chemistry, physics and astronomy. By the time I was in fifth grade, I was trying to decide whether I wanted to become a physicist or a biologist. It was finally a computer graphical representation of DNA replication displayed in Carl Sagan's documentary Cosmos that made me decide to become a molecular biologist. I was 12 years old.
How did your father's political connections help you explore your thirst for science?Neither of my parents had a background in science. My mother studied English philology/linguistics and philosophy, and my father had law degrees. At foreign service school, which was the training ground for most of the Spanish foreign ministry, my father was well connected with the political elites. When I told my father that I wanted to do molecular biology, he sent me to his friend, the minister of education and science, who introduced me to the director of Spain's molecular biology institute. I would then meet Gines Morata, a faculty member at the institute. He encouraged me to read college-level textbooks and told me to specifically come to UCSD and the Salk once I graduated from high school.
Most teenagers find their first job at the local mall or the fast-food drive-through window. What was your first job, and where was it?My first job was actually as a stunt man for commercials. In high school I was doing gymnastics, and a booker of Maroe, the oldest modeling agency in Madrid, asked me to do a few commercials.
Rumor has it that you did some fashion runway modeling and some campaigns for Adidas and the United Colors of Benetton.
After I showed up at the agency a few times, my booker introduced me to the owner of the agency. She placed me on the fashion side of the agency, so I ended up working as a model for various commercials, including print. Among them, for a couple years, I did runway every season for Benetton, being the only Asian around, despite the fact that I was just a little too short to make the 6'0" height cutoff for men.
What are the main areas and focus of your research at the Salk?
My main area of work at the Salk is the breast and ovarian cancer gene BRCA1 and its function. I have been working on this since my Ph.D., which I also did at the Salk. We found that BRCA1 is responsible for maintaining the most silent regions of the genome, and loss of this silencing can lead to making too much of a molecule called satellite RNA. This satellite RNA, when in excess, is able to break DNA and presumably cause the mutations that are the ultimate cause of cancer. So in the end we have worked out what BRCA1 really does at the molecular level. I also work on stem cells, and right now we are most interested in how stem cells get generated and why cloning works from an evolutionary perspective. Essentially, I am looking for the "reset button" of the biological program that makes stem cells.
You recently discovered how the mutation of the BRCA1 gene leads to breast and ovarian cancer. How may this finding help physicians detect cancer earlier in patients?
As mentioned before, the loss of BRCA1 leads to making too much of a molecule called satellite RNA. If we were able to track this molecule—let's say in a blood sample—we could in theory track the progression of cancer. Whether this is really possible we will have to test in experiments. Current technology only determines whether someone is predisposed to cancer— i.e., if you have the bad versions of BRCA1, chances are at some point in your life (if you are a female with a BRCA1 mutation), you will develop a breast or ovarian cancer, but when exactly is unknown. This test would tell you in theory if the cancer is starting to develop.
So this discovery could allow clinicians to follow the cancer in real time?
In theory it would be something similar to the PSA test for prostate cancer, in which you regularly take blood tests, and if the levels of PSA, or in this case satellite RNA, spike, then you need to have follow-ups to find out where the cancer is and surgically excise it.
You spent nearly ten years on this research. What drives you? Why have you chosen a life dedicated to science?
I never considered any occupation other than science. Everything else will be more or less recapitulating something that someone has already done before. I just find it more satisfying to work out something that has not been done before and solve problems that were neglected or ignored by others because the time or the technology was not ready when the questions were first posed.
What do you hope your scientific legacy will be?
I hope that one day I will uncover an elegant fundamental insight that ties together a large number of observations—something that will be unifying under a single elegant principle, much like what physicists aim to do. I am still far from it, but it does not hurt to dream about it.
What are your top five essentials? Things you can't live without for your work and personal life?
I guess for me there are only three sine qua nons: science; physical exercise, especially rock climbing; and occasionally trance, house and techno music.