An Interview With Daniel Douek, M.D., Ph.D.
Daniel Douek, M.D., Ph.D., is an internationally recognized leader in the field of human immunology and chief of the Human Immunology Section of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Earlier this year, Douek assumed the chairmanship of amfAR's Scientific Advisory Committee, a volunteer group of experts in the field of HIV/AIDS research who help guide amfAR's research program.
You recently became chair of amfAR's Scientific Advisory Committee. What do you think you can bring to the role of chairman?
I've got almost 20 years of experience in research, most of that in HIV, all of it in immunology, mostly in human immunology. I think that's all particularly important for the future, which really looks toward translating basic research into clinical trials in people. That's what I've been doing over the last 20 years. Given that background -- as a translational scientist in the truest form of the term -- I think that puts me in a good position to help guide the kind of research that amfAR might want to champion.
Has amfAR ever played a role in supporting your own research?
Well, the first grant I ever got as an independent investigator was an amfAR grant. It was to study a certain aspect of the immune response to HIV. And I'm still doing it; I'm still doing that project. It's much more advanced, using new technologies. But that's what set me off as an independent investigator. So I have a lot of thank amfAR for [and] I will be forever grateful.
Can you tell us more about your work?
I'm interested in HIV disease pathogenesis and prevention. I want to know why some people get infected when they're exposed, and other people don't. And why some people progress rapidly, while other people progress less rapidly. And I'm trying to understand virus factors and host factors.
In terms of my involvement in the cure field, I'm really trying to understand which cells are infected; which cells carry latent virus -- which subsets, which anatomical sites -- what is it about a cell that makes it susceptible to infection, where another cell is resistant. These types of questions are important, so that we can target our cure approaches to particular cell subsets. There might be a common theme between those cells -- a set of genes that are turned on or turned off or something that makes them the prime cells that harbor latent live virus.
Let's say you're a betting man. If we divide cure research into three basic approaches -- pharmacologic, immunologic, and cell therapy -- where would you put your money?
Well, I never bet because, remember, betting is rigged to make money for the casino! But, if I were to say which one is the best option ... it's probably going to be a combination of all three, and that's the approach we need to take. The reason there is persistence of virus in people is multifactorial. So the therapeutic approach, I bet, is going to be multifactorial.
There you go, I just bet!
In your opinion, what are the biggest challenges standing in the way of a cure?
They are the reasons why HIV becomes a persistent infection. One of them is, it infects CD4+ T cells and kills them, so you've lost your immune system, or are severely immunocompromised. Number two, the virus escapes from the immune system rapidly, so immune therapies are at a disadvantage. And number three, the virus integrates. So basically, it becomes a host gene.
"... the goal is to make sick people better. That's it. It's no more complicated than that."
You mentioned that HIV weakens the immune system by quickly killing off the body's CD4+ T cells. So even if someone is cured, aren't they still immune compromised, despite being free of HIV?
I think they would remain immune compromised. The longer I spend in this field, I think I'm coming to the realization that immune reconstitution needs to be more robust, and it should be part of the actual cure approach itself. Not just getting rid of the virus, but repairing the immune system too.
I think that's something we really need to think about, because if you look at the lifespan of people who are infected with HIV, even if they are on antiretroviral therapies, and particularly if they've started on antiretroviral therapies when they have a low CD4+ count, their lifespan is reduced. And I think that's intimately linked to the immune compromised state.
What prompted you to pursue a career in AIDS research?
I always wanted to do research. I've always been an immunologist, since before going to medical school. And I really became interested in human immunology during my Ph.D. Human immunology is a newish subject, in a sense. It's different from the old-style mouse immunology. With human immunology, you have to approach it completely differently. You have the people who are infected with something, and you have to design your experiment around that. You can't cause the infection in people. So you have to deal with what you've got. You have to be a little bit more inventive.
The advent of HIV has really helped the field of human immunology come to the fore, because we had to do something quickly. So that whole arena was very attractive. Also at the end of the day, it sounds kind of trite, but I do what I do because the goal is to make sick people better. That's it. It's no more complicated than that. We learn a lot of stuff, and that's all very nice. But the goal is to make sick people better. It's a fantastic challenge. It's difficult, but I can see the light at the end of the tunnel. It's there.
So you are optimistic we will find a cure for HIV?
I am optimistic by nature. I look at it like this: Before the spring of 1922 if you had a diagnosis of diabetes, they sent you to a sanatorium to die. A few months later, that same year, enough insulin was being produced in laboratories, and then you lived. It's as simple as that. So, for me, that is the light at the end of the tunnel. We know that we're going to succeed. We just have to find a way to do it. But I have total confidence we will. It's going to be difficult and it may take some years, but we will.