INTERVIEW

Huda Akil

Interviewed by Dan Ferber

Posted December 7, 2001 · Issue 116

Background

Biography
"We live in a world filled with stress," says Huda Akil, the new president elect of the Society for Neuroscience, and she has made a career understanding how our brain deals with it. Growing up in Damascus, Syria, and in Lebanon, she was fascinated by how people think and feel. That early interest led her to study psychology at the American University in Beirut, where she earned an undergraduate degree and did master's work in psycholinguistics. As a graduate student at UCLA and a postdoc at Stanford University School of Medicine, she helped discover the endogenous pain-relief system in the brain, and showed that stress made it kick in. She has done three decades of pioneering work on the neurobiology of stress, pain, and depression, advancing understanding of the role of the brain's own glucocorticoids and endorphins. She and her husband, Stan Watson, are codirectors of the Mental Health Research Institute at the University of Michigan.

What event led you into research and this area of research?

I've always been interested more in the mind, if you will. When I was a kid I was interested in understanding how we think and how we feel. I went into psychology thinking that that would help me understand. I did my undergraduate work at the American University of Beirut . . . in psychology. I grew up in Damascus and in Lebanon. I started to do a year of master's work [in psycholinguistics] at the American University in Beirut. And while I was there I got interested in language, thinking that language would help me understand thinking. . . . While I was [getting the master's degree] I took a course in psychobiology. I found it fascinating, and in particular I started reading this book by a man called Jim Olds. He had first shown that there are parts in the brain of animals that if you electrically stimulate them, you seem to give the animals pleasure. They would go and work really hard to stimulate that part of their brain over and over, to the expense of even eating or drinking - it was very potent drive to self-stimulate. It was called self-stimulation.

I went to the library and read everything he had written. I realized that that was one way for the brain substrate of behavior - of emotions, of feelings, motivations - to cause animals to behave a certain way. I wasn't used to thinking about the brain substrates of behavior in this kind of way. . . . I hadn't realized how you could have physical structures and chemical structures that were going to actually mediate these behaviors. I hadn't thought of how you do that, how you begin to study that. And this was just by happenstance, something I read that I found fascinating.

When I came to the U.S. to get my Ph.D. [at UCLA, working with the late John Liebeskind] I decided to go into psychobiology. John Liebeskind had actually worked with Jim Olds. John had become interested in the biology of pain; that also was using brain stimulation techniques. So I got involved in that, and was part of a group that found that there are brain regions that we could electrically stimulate, not so much for just pleasure, but to block pain.

In 1972, as a graduate student, I gave a talk at a pharmacology meeting in [San Francisco]. In the audience was a man called Hans Kosterlitz, who, along with John Hughes, was convinced there were opiate receptors and was searching for ligands. This was the group that identified enkephalin, the first endorphin. He was in the audience and was interested in our findings. He asked if [we were] going to purify this thing . . . I stayed in touch with that whole field and when enkephalins and endorphins were discovered, I became very interested in understanding biological function ... in pain control, and in the whole field of opiates.

As a postdoc, at Stanford [University School of Medicine] in the lab of Jack Barchas, we showed that stress could activate endorphin, and endorphin in turn could block pain. We showed that in animals and in humans. Then my husband, Stan Watson, and I got very interested in the basic biology of endorphins and the stress system. Suddenly we were both in the pain and the stress business.

Who has most inspired and/or influenced your work?

I've had some terrific mentors. John Liebeskind and Jack Barchas were wonderful mentors and they have affected both my specific knowledge and my style of how you go about posing questions and answering them, what you value in science, and that sort of stuff.

In terms of more recent scientific input, there are people in the field, obviously, whose findings have had a big impact. Bruce McEwen would be one of them. He is a real huge leader in the field of stress. He has done beautiful work and has produced wonderful graduates. Ron deKloet, who has done work on the steroid receptors . . . he's a very interesting man. Also Seymore Levine, who does developmental work.

Who awarded you your first grant and what was it for?

My first grant was from NIDA [National Institute of Drug Abuse], and it was a postdoctoral fellowship to go to Stanford and work on endorphins. Actually to work on stress and pain before endorphins, but it turned out to be for endorphins.

Also, I got very important money from the Sloan Foundation. I had a Sloan fellowship as a postdoctoral fellow. It gave me the flexibility to go wherever I wanted to. So my husband was trying to get a residency, and he wound up being a resident in psychiatry at Stanford. It was hard to coordinate careers, so having the Sloan fellowship made a huge difference.

What was your best idea or theory?

It's yet to come! I always like the latest one. I'll tell you what interests me most: it's not my best. This idea of the timing of emotions - how we manage our emotions; what is the circuitry and what are the mechanisms that lead us to change from one feeling to another or get rid of one feeling or move on to another. I really think that is the heart of the matter in terms of . . . mental health and also combatting mood disorders.

I don't think that people with mood disorders are feeling anything aberrant or unusual; it's how they get stuck on it. And it causes a lot of pain and suffering, and it has both emotional and cognitive consequences. It affects your beliefs about the world and so on. It's a matter of how you shift gears and stop being stuck. If we could understand that. . . .

You can think of this as mechanisms of plasticity, mechanisms of how quickly our circuits are able to [alter] their activity, or you can think of it at a more psychological level. I think regardless, the moment-to-moment life of the brain, and how it evolves and shifts and plays like a music, if we could understand that, I think it would be lucky. I think it might require not just the kind of research that we do, which is static, but trying to come up with more dynamic ways of studying [brain] processes.

I think how humans go about fine-tuning . . . there must be mechanisms, and they must be different from animals. . . . It must have a molecular basis, the dynamics over time, and I think that really needs to be understood.

Which scientific idea (yours or others') do you regret the most?

I regret the separation between affect and cognition. I think it has made us think in compartments too much. When I think about learning and memory, I think it didn't evolve so we could do higher order math. Really, it's an innate part of survival. You have to remember where you've hidden the food, where are all the good males or good females. Where it's safe, where to make a nest for your babies. You have to learn about the environment, you have to learn how to move and talk.

So learning and memory are so tightly intertwined with motivation and affect. And affect and motivation are such important influences of what we learn and what we remember, how we think back on it. And all that comes together in belief systems and so on, which is really the intermingling of cognition and emotion.

We have officially called these things cognitive neuroscience and affective neuroscience. The fields don't tend to talk to each other. For years, for example, people studying the hippocampus - we knew there were steroid receptors there and these were probably relevant to stress and emotional behavior. At the same time, people who were studying the hippocampus were focusing on [its role in] learning and memory. It took many years for those things to come together.

Sometimes, just because we try to categorize things for our own convenience, we become victims of it. And that hurts our sense of fluidity, our ability to think laterally and link things up that need to be linked.

What are your scientific plans for the next five years?

I would like to understand the molecular basis of differences in emotionality and then take that to an understanding of human mood disorders. [I'd use] a combination of genetic techniques, including actual genetics in living humans . . . and animal studies, to shuffle back and forth to keep challenging myself and the scientists around me, and have them challenge me, into thinking about what makes us emotionally different, and how that interplays with a lot of other things to make us either resistant or prone to mood disorders.

What advice would you give to a researcher starting out?

I would say, don't be too tight about your ideas. Be open to both ideas and criticism. Don't take it personally. Expand your mindframe. And don't be scared of failure, because it's part of the scientific process. If you're not failing you're not stretching. If you're not falling in the beginning, at least you're not pushing yourself. So don't play it safe intellectually.

If you could work with any scientist (historical or current), who would it be?

I'd work with Darwin. He really had a huge picture of all of life. It was built on people who came before him, but he reframed it. . . . The amazing thing is he did it not with very fancy technology, but with thinking and observing and restructuring his thinking over again, until it became very theoretically elegant.