View from a Zeppelin:
Interview with George Koob
Mika Ono of News&Views caught up with Scripps Research Professor George Koob to ask him about his new book, "Neurobiology of Addiction" (with Michel le Moal, Academic Press, 2005). Here, Koob shares his thoughts on the process of writing the book, what it says about the state of addiction research today, and how that in turn has influenced his work in the lab.
News&Views: Why the book?
Koob: One of my postdoctoral fellows, Noelle Gracy, ended up in a job at Academic Press. She had observed a gap in the literature in the area of the neurobiology of addiction and asked whether I would be willing to write a book.
So, one year at the Society for Neuroscience meeting, Noelle, Michel Le Moal [of the Université Victor Ségalen Bordeaux in France], and I sat down and sketched out an outline. Along the way, Academic Press was acquired by Elsevier, Noelle was transferred to Amsterdam, and the project was taken over by editor Johannes Menzel. Johannes was unrelenting—he wasn't going to let us out of doing the book.
N&V: Could you tell me about the process of writing it?
Koob: Michel and I wrote different sections. He edited everything I wrote and vice versa. Importantly, since he's a psychiatrist from Europe, Michel's expertise complements mine. We wrote the whole book ourselves. There are no invited chapters. We were originally going to write something closer to a textbook, but when we got into it we couldn't stop adding references and exploring more information.
First, we wrote a prototype chapter on cocaine and stimulants. Then, we moved to opiates, then alcohol. By the time we got to the alcohol chapter, we realized how enormous the task was.
Each chapter for a given drug class stands on its own, with an introductory section, which even the lay public might enjoy reading, then the neurobiology, which gets very complicated. Toward the end, we decided to try to integrate all the theories of addiction with a circuit diagram. And in the last chapter, we present our own views.
We were supposed to have the book done by fall 2004, but delayed it a year, then again another few months. I started getting up early in the morning and writing for three or four hours. That's basically what I did for a year. Last January, February, and March, Michel and I did nothing but write. He would fly over for a few days from France, or I would go to Bordeaux. Johannes insisted we had to finish by March.
N&V: Are you glad you wrote the book?
Koob: Yes, I am, at least on one level. It did take a lot out of us meeting the deadline. But if you don't have the deadline, you don't do it. So it's a Catch-22. My advice to anyone who wants to write a book is to make sure you understand there are deadlines.
N&V: What surprised you when putting the book together other than the timeline and the volume of material?
Koob: There were a couple of surprises. One was how little is known about addiction, as opposed to what drugs do to you initially. It became clear that the field needs to move to a study of dependence—the compulsive use of drugs—from whether or not they make you high.
A few common elements of addiction stood out in the human studies. One is that the frontal cortex doesn't work if you're an addict. The other is that your dopamine system probably doesn't work well either. That's not a big surprise, but many people in the field think you have more dopamine if you are an addict. Actually, it looks like you have less.
Other common elements in addiction, which I addressed in my recent faculty lecture, are the activation of the brain stress system and the hormonal stress system. These may play a bigger role than previously thought.
Overall, there's still a huge gap in our understanding of how molecular changes translate into cellular changes, which translate into circuitry changes. We're just starting to move away from the idea that these chemicals are floating around in our brain in pools of varying levels. Clearly, interactions are occurring in very specific areas at very specific times. How molecular changes occur to make one person more vulnerable to addiction than another is really the key to the addiction process.
N&V: Has writing the book influenced the direction of your work?
Koob: Yes, it has. Writing the book was like being in a zeppelin, one of those big rigid-frame balloons that float over Torrey Pines during a golf tournament. Looking down from a zeppelin, you can see all of the Torrey Pines mesa, all the changes that have occurred, and the size of Scripps relative to everything else. When you are floating above the field of addiction, you can see more clearly what work is important and what isn't worth doing any more. So, for example I'm not interested in pursuing much work on dopamine anymore, since there's an overemphasis on dopamine research in the field. On the other hand, I'm more and more intrigued with the frontal cortex. I have new postdocs who are going to be working in that area.
N&V: Did the book give you any other practical insights?
Koob: The global perspective has been helpful for running the Integrative Neuroscience Initiative on Alcoholism consortium and for understanding how our department [the Molecular and Integrative Neurosciences Department] and TSRI can help me address some of the key problems of addiction.
For example , I now have collaborations with several investigators in Chemistry, and [Professor] Ben Cravatt and I are going to be talking about some potential collaborative efforts. I have come to realize the resources at Scripps Research that we can apply to problems.
The book can now become a resource for us at the institute. We can use it for teaching medical students, pharmacology students, and graduate students. Ultimately, that's going to be the value to the scientific community. It will make it easy to find the figures we need and go to original sources. If we missed an original reference, it's not because we didn't try—some of them go back to the eighteenth century.
Everything in the book is superdocumented by [Scripps Research Senior Research Assistant] Mike Arends. Janet Hightower of [Scripps Research] BioMedical Graphics helped with the diagrams. To do a book like this, you have to have a good support team and we certainly did.
N&V: Why did you insist on original references?
Koob: I've seen so many textbooks for undergraduates that say the same thing and are close to plagiarizing famous pharmacology texts. When you go back and check on some of the statements, they have taken on a life of their own. They're not even true. A good example is that there is really no evidence for the widely cited statement that 60 milligrams of nicotine will kill you. There is a discussion of it in an old paper, but that's about it. There's no data.
N&V: Any other thoughts related to the book?
Koob: Well so far, no one has thrown any tomatoes! I haven't gotten any irate emails—but maybe it's too soon. It's only been a couple of months.
Send comments to: mikaono[at]scripps.edu