Understanding How Molecular Changes in Malaraia Carrying Parasites Change the Disease and its Transmission

We are working on trying to understand the parasite and its interaction with both the host and the mosquito. We’ve taken a genomics approach, so we are using the revolution in the DNA sequencing to examine the parasite at a molecular detail. One of the interesting things that we are trying to understand is how changes in the parasite result in changes in the disease and in its transmission by the mosquito. For example, we’re trying to identify the region of the genome that is associated with the drug resistance phenotype.

I come from a basic science training background. I was a zoology major in college. I came to graduate school to learn molecular biology and cell biology, and I really thought that was what I was going to do in a very basic science way, when I took my post-doc. I became a post-doc at the Harvard BioLabs, and during that period, my department had a retreat, where all of the faculty talked about their research. And Conrad Block, who is a very famous chemist, got up and said, ‘You know, I’m not going to talk about my research. I’m going to talk about the World Health Organization and this meeting that I just got back from.’ He’d been invited by the World Health Organization to advise them on how to apply modern approaches to biochemistry and drug design to important tropical diseases, and malaria had captured his attention. He found it fascinating that this organism actually invaded a human red cell and then set up housekeeping inside the human red cell. And I still remember thinking, ‘I can’t possibly be interested in something like malaria’. Yet, I sat there, and I thought to myself, well this is really pretty interesting from a basic biology standpoint. And as he talked, I realized what an important disease this is.

He went on to talk about the problem of drug resistance, the problem of transmission, and how this disease was a big public health problem. I decided at that moment, that that was what I was going to work on. I still remember it as clearly as today. I would never advise one of my students to do that, to just take up an entirely new subject at the time of their postdoctoral work. But, I decided that this was a time that was ripe for using the skills that I had learned – molecular biology, cell biology, biochemistry – but now applying it to this very important public health problem. The School of Public Health took a chance, recruiting me to the faculty with no experience in malaria to set up the malaria research program HSPH. So I spent the next 5 years setting up my lab and learning about malaria. And I have forever, ever since worked on malaria.

“So I have, so what I did you know a decade ago, is that I spent every day in the lab doing lab experiments, growing the parasites, or I was in the field collecting patient samples. But now, I have sort of my schedule is, on Monday, I have a day of writing and discussing on specific projects what the progress is. On Tuesday, I spend a day in which I meet with all of the people working on the malaria research projects. You know sort of sequentially throughout the day. I get updates essentially Monday and Tuesday. On Monday I do special projects, [and] on Tuesday, I speak with everybody working in the group. On Wednesday, I run the department, so I meet with all my administrators and deal with the sort of questions of running an academic department at Harvard. On Thursday, I spend the day at the Broad, where I’m a senior associate member, where all the genomic work originates, and again I spend the day in research meetings. And on Friday, I have a day on catch-up. I use that for writing or reviewing projects, or dealing with administrative issues. These days, I probably spend about 60% of my time on research, but on a much more, you know I don’t do experiments in the lab day-to-day, and about 40% of my time, not only running the development but also developing academic curricula, leading the Harvard Defeating Malaria: From the Genes to the Globe. So I spend a fair amount of my time now looking at the broader questions of how, going forward, Harvard and the world are going to deal with malaria.

“This is part of how the scientific world and its part of how the academic world. That people who have been in academia and have been successful then generally take on larger responsibilities of making sure that the next generation. I mean my goal is to train the next generation and the next generation to lead wherever the field takes them. I mean, if that means if it’s doing Wolbachian mosquitoes that’s great, or if it is doing synthetic vaccine design or whatever.”

I’m an active snowboarder, windsurfer, and then bicyclist. I’m a better snowboarder and bicyclist than I am windsurfer, I have to admit. And now I’m taking swimming lessons, so that’s partly so that my windsurfing gets better.

– Mice, Men, and Malaria
– The Biography of Amelia Earhart

I think you have to follow what you are interested in. I would say I was fundamentally interested in science. I found biology fascinating. And that’s still true. So I think you find what you love and then you just do it.

Over the last 5 years, I’ve really become convinced that having the goal of eradication has sort of galvanized the field into thinking about new strategies to interrupt transmission, and new strategies to control this disease. And I think that is one of the most exciting changes in the field. We now are thinking not about controlling the disease, but in fact about completely eliminating this organism from the world.

I come from the medical biology side, but there are all these other factors that make an important different in this disease: access to medicine, access to health care, empowerment, economic issues, and governance issues. I can discover the absolute best molecule to kill the liver stage of the parasite, but if there isn’t somebody who can convert that molecule into a drug or a vaccine, it’s never going to go anywhere and help someone. You need people who are really experts in their field, but they have to be willing to make connections. And that’s a challenge, right? When biologists think about interdisciplinary activity, they think about a molecular biologist and an immunologist coming together. That’s not what I mean. What I mean is a molecular biologist and a policy person having a common problem. They both understand what it is going to take to change the world, and they’ve got to figure out how to make both of those pieces come together.

Still, the problem of malaria is a problem of disease endemic countries, not a problem of the United States. In the end, there has to be a drive from the population that is affected for better health. And I think that’s happening. Educating disease endemic country scientists is very important. Not bringing them here and then keeping them here, but in fact educating people in the context of their own environment so that they can become the leaders. Malaria in Senegal is changing because the Senegalese want to change it, not because I want to change it. I think our specific role is to give them science so that they can create the evidence.

I think it’s this generation of students. If malaria is going to be eradicated, it is going to be by this generation of students, not by me. My goal is to train the next generation and the next generation to lead wherever the field takes them.