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Posted: 15 Mar 2012
Career Pathways: José Esparza

Dr. José Esparza describes his journey from being a medical student in Venezuela to a senior advisory position in the Bill and Melinda Gates Foundation.


José Esparza at-a-glance

  • Received his MD from the University of Zulia in Venezuela (1968), and his PhD in Virology and Cell Biology from Baylor College of Medicine, USA (1974).
  • From 1974 to 1985 he worked at the Venezuelan Institute of Scientific Research in Caracas, Venezuela, where he became Chief of the Laboratory of Biology of Viruses, Chairman of the Centre of Microbiology and Cell Biology, and Professor of Virology.  Dr. Esparza has worked on different aspects of human virology, focusing on the study of Rotaviruses.
  • He then joined the World Health Organization (WHO), in Geneva, Switzerland, where he became Chief of the Biomedical Research Unit of the WHO Global Programme of AIDS (1986-1995).
  • Dr. Esparza then became the Coordinator of the WHO-UNAIDS HIV Vaccine Initiative in 1996 at the United Nations Programme on HIV/AIDS (UNAIDS).
  • In 2004 he joined the Bill & Melinda Gates Foundation to work on HIV vaccines.

As a Venezuelan scientist, what was your biggest challenge moving to the U.S. to do your PhD work?  Why did you return to Venezuela?

It was a multi-step process. The first challenge (which I guess is common to many people who come to the US for education) is to return to your home country after receiving the PhD or finishing a postdoctoral training.  There is always the temptation to stay in the US and to continue a scientific career here. In my particular case, I decided to return to Venezuela to do science in my home country. That was back during the optimistic years of the mid 1970s, when it was possible to do science of international caliber in low- and middle income countries, and at the same time, to help address local problems. One thing I did was to change the topic of my research. My PhD thesis was on the genetics of herpes virus type 2 (at that time we thought that it was associated with cervical cancer!). However, I decided to work on viral diseases of national/regional importance. That was a risky decision because it required me to start an entirely new line of research. Fortunately, my training at Baylor with the legendary Joseph (Joe) Melnick, gave me a solid and broad background in virology. 

I decided to work on Venezuelan Equine Encephalitis (VEE). In addition to being the national eponymous virus, it was also the virus that initiated my passion for virology when I was a medical student. In 1962 there was a major epidemic of VEE in the Goajira peninsula, near my home city of Maracaibo, that caused significant morbidity and mortality. As a young medical student interested in science, I was fascinated by the complexity of VEE, the biology of the virus, its complicated epidemiology (vectors, reservoirs), affecting both animals and humans. That exposure to a viral epidemic made me decide, very early in my career, that I wanted to dedicate my life to the study of viruses.

You also made significant contribution to the early studies of rotaviruses. What prompted you to expand your research in that direction?

At that time, 1974, I was very curious about the etiology of diarrhea. We knew that bacteria was associated only with a certain proportion of cases, but many years of virus research had failed to show any clear association of diarrhea with viruses. Thus, at that time the dogma was that “viruses do not cause diarrhea”; besides, we had a beautiful mechanism to explain how bacteria cause diarrhea, and there was not an evident one to explain how viruses could do it. 

In 1973 a new family of viruses was discovered to be associated with diarrhea, the rotaviruses. I immediately began to work on rotaviruses starting with epidemiology. It took several years and many studies to convince the scientific community that rotaviruses were a major cause of gastroenteritis. My laboratory in Venezuela also worked on the molecular biology of rotavirus, and we published studies on its ultrastructure, protein composition, molecular cloning of its genes, generation of monoclonal antibodies, etc. Through this work I was addressing my two major needs - working on a problem that was important for my country and, at the same time, contributing to what I call “the universal treasure of knowledge.”

In 1981 I returned in an extended sabbatical to the US (Duke University in Durham) to work with Wolfgang (Bill) Joklik. Rotaviruses are double-stranded RNA viruses and I wanted to know more about that group of viruses. Bill’s lab was one of the top places working on Reoviruses (the prototypic ds RNA viruses). That was another important decision in my career. Instead of staying in the comfortable niche of rotavirus epidemiology, I wanted to learn from the better studied Reoviruses, to translate that knowledge to Rota. It worked!

Many years later, after I had left that field of research, a rotavirus vaccine was developed, and it has contributed in a spectacular way in the reduction of morbidity and mortality caused by diarrhea!!!

What made you decide to shift from lab work to join WHO--?  Did you always want to pursue a career in an international organization or funding organization?  

In the mid-1980s the economic situation was difficult in Venezuela. In 1985 I applied for a grant from the WHO in Geneva. To make a long story short, I did not get the grant, but instead they offered me a job. They were looking for someone who had the developing country experience but also understood modern molecular biology. So, I decided to test the waters and spend a couple of years in Geneva. I stayed there for 20 years!

WHO was considering launching a program for vaccine development, harnessing science to develop vaccines for global health, and they thought that I could contribute. I was fascinated with the possibility of using science to solve problems at a global scale. That is how my second passion in science started: vaccines.

In WHO I started to work at the Division of Communicable Diseases. My first assignments focused on viruses with epidemic potential - yellow fever, dengue, hemorrhagic diseases, etc.; those were the emergent viruses, although at that time we did not use that terminology.

But a year later Jonathan Mann was recruited to start what became the Global Programme on AIDS (GPA).  Because AIDS was caused by a virus, Jonathan needed a virologist and he asked me to join GPA to establish the Biomedical Research Unit (to deal with diagnostics, therapeutics and vaccines). Eventually I focused on vaccines, a task that I continued when in 1996 I moved to UNAIDS (a new program that inherited most of the WHO activities on HIV).

What was the most significant change in leaving the WHO and joining the Bill & Melinda Gates Foundation? What were the opportunities and challenges?

In 2003 we learned of the failure of the VaxGen trials and we felt the need to organize ourselves better to harness science to develop an HIV vaccine. That was when Rick Klausner at the Foundation proposed the idea of the Global HIV Vaccine Enterprise, and I was one of the co-authors of the paper published in Science. I did work with Rick from Geneva on the Enterprise concept, and in 2004 Helene Gayle, at that time the HIV Director at the Foundation, asked me to join. I asked for a leave of absence in UNAIDS and came to Seattle. Again, I was pursuing the opportunity to harness science to solve public health problems and the Foundation had the resources and approach to make a difference.

At the Foundation we launched the CAVD (Collaboration for AIDS Vaccine Discovery) and strongly supported the collaborative concept of the Enterprise. There is no doubt that the Enterprise concept has been accepted by the field, and today the different agencies working on HIV vaccine work together in a way that was unthinkable a few years ago.

What has been the most rewarding moment of your career? And what was the most difficult decision in your career? 

My major moments of reward are when I see the success of young scientists from the developing world that I have helped in some way.

The results from RV144 also provided enormous satisfaction. While at WHO, I worked with Thailand for many years, helping them with their HIV vaccine activities. RV144 is as much the triumph of the scientists and agencies that did the trials, as of the country of Thailand that for many years supported the process. I was so happy when last year Princess Sirindhorn gave me a plaque in recognition of my more than 20 years of work in Thailand.

The most difficult times I remember were when we learned of the failure of the VaxGen trials in 2003. But we did not give up, and today we are still learning much from the samples from those trials.

I have now transitioned to a new position in the Foundation (Senior Advisor on Vaccines). That is a challenge and an opportunity. The HIV vaccine field has remained isolated for too long. There are lessons from other vaccines that we can use for HIV, and vice versa. I hope that now I can help with that.

What will it take to get an HIV vaccine?

Now, after the RV144 trial, we know that we can develop a vaccine that prevents infection. We should focus on that. Now is the time to be more disciplined on the candidates we develop, with clearer gates for decision making, and a more systematic approach to down-select candidates. The time for “me-too” HIV vaccines is over. And we need to do HIV vaccine research with a real sense of urgency. It is not only about producing nice science. It is about addressing a major public health challenge. I would like to see a more rapid progression of candidates to clinical trials. And if they are going to fail, we should know that quickly.

But this is a much longer conversation!!!

What advice would you give to young scientists seeking careers in research-funding organizations and/or international organizations? What skills are necessary? What’s the best way to get a foot in the door?  

Don’t plan for it. Working in a research funding or international organization is not a career. It happens when it happens. My advice is to work on what you are passionate about. Your passion and achievements will take you to the right place at the right time, but you have to be willing to take risks.

I heard from Bill Foege the following advice: Live your life according to what you would like to be written in your epitaph.

Editor’s note: Don’t miss: Bill Foege’s “House on Fire” - it’s an interesting read about the fight to eradicate smallpox.