High Price

doing more brain surgery on them. I knew that I was well prepared to do the lab work.

    On my recruitment visit to the University of Wyoming, Charlie took me skiing. It was my first and last time skiing.
    I wasn’t so sure about the classes, however. Thankfully, before starting graduate school I spent a week in May with my girlfriend Terri’s father. He lived in Longmont, Colorado, and taught me a critical lesson that paved the way for my graduate school success. Terri’s father had served in the military and was an information technology consultant. He said that the most important thing for me to do in grad school was to ask questions when there was something I didn’t know.
    I sort of nodded politely when he told me; it seemed obvious. Of course, if you don’t know something, you need to ask about it. I’d always worked under that principle and had not been embarrassed previously to ask what might be seen as dumb questions. That had long been one of the keys to my educational success.
    But he stopped me. He could see that I wasn’t hearing him. “No, seriously,” he said. “This is important. If you don’t know, you have to ask.” I suddenly realized why he was stressing it: he knew I might feel that since I was now a graduate student, I would have to start pretending that I knew things I really didn’t know. I might be embarrassed, at this new level of recognized achievement, to admit ignorance. He was right.
    And if I hadn’t followed his advice, I probably never would have gotten my master’s, let alone a PhD. With my background and the holes in my early education, there were many important things I didn’t know. I had to be brave enough to ask what others might see as obvious questions. Not learning key things I needed to know for my work would be worse than possibly looking ignorant for a moment. And often, it turned out, other graduate students were similarly baffled by the “dumb” things that I thought I should have already known.
    Indeed, this is why teachers often say there are no dumb questions: sometimes the most important discoveries come from questioning seemingly axiomatic assumptions. One such assumption during my graduate training was that dopamine was the “pleasure” neurotransmitter, and that drugs like cocaine and nicotine produced pleasure by increasing the activity of this neurotransmitter in the brain. Seminal evidence for this view came from studies of rats trained to press a lever to receive intravenous injections of cocaine or nicotine. For example, when rats are given an opportunity to self-administer cocaine, they do so robustly. But when given a drug that blocks dopamine several minutes before having an opportunity to self-administer cocaine, well-trained rats initially work harder to receive cocaine injections but eventually give up, presumably because the dopamine signal is being blocked. Researchers interpreted the rats’ initial burst of responding as an attempt to compensate for the lack of pleasure due to dopamine blockade.
    With nicotine, however, under identical conditions, rats do not display the burst in responding; instead they stop responding immediately. Despite the fact that the rats’ behaviors were different depending on the drug—cocaine or nicotine—many researchers’ interpretation remained the same. That is, in both cases it was interpreted that the animals were no longer able to get the pleasure experience they’d come to expect, because dopamine was being blocked. My question was, if so, then how could both responding more and responding less be interpreted the same?
    I never received a satisfactory answer. At best, someone would say, “Good questions.” Later I began to realize that the dopamine-pleasure connection was far more complicated than the way it was being described.
    The more I studied drugs, in fact, the more I learned about these types of basic inconsistencies in our ideas about them. Back then, however, I was simply excited to be part of the scientific conversation and didn’t dwell much on it. I found a study partner early on—doing so would be another key to my success—and settled in to do the work. My graduate work consisted of not only research and coursework but also teaching undergraduate courses. During my first year of graduate school, I served as Charlie’s teaching assistant for his Drugs and Behavior course. I taught the course on my own during my final three years of graduate school. By the time I had