Robert J. Lefkowitz M.D.

While it doesn't compare with Feynman's memoirs, this is still very readable and occasionally funny. I appreciated reading Lefkowitz's blow-by-blow description of the Nobel award festivities. Usually this is somewhat glossed over in memoirs, but Lefkowitz is obsessed with scientific competition and recognition, and isn't ashamed to boast and glory in it. I appreciated his self-centered honesty, though I'm still not quite sure that I get the point of racing to do science ahead of two or three other groups doing the exact same thing in parallel—what novelty are you contributing? There is a good mixture between science and personal stories.

> To efficiently deal with the deluge of offers I was receiving from other schools, I composed three different generic letters turning down such requests. These three letters conveyed varying levels of angst, with the amount of angst being proportional to the stature of the university. Letter C was polite and brief. Letter B was longer and indicated a higher level of angst. Letter A was reserved for inquiries from the top universities in the country.

> Many young scientists in the early stages of their independent careers get distracted by constantly chasing the Bigger Better Deal. I have always subscribed to the simple idea that if it ain’t broke, don’t fix it.

> In the 1970s, many people were skeptical that receptors existed. … At a national meeting in 1973, I presented a talk outlining my belief in receptors as physical entities as well as my aspiration to prove their existence. This talk was followed by a discussion panel featuring the legendary Raymond Ahlquist as a member. Ahlquist was the researcher who, in 1948, first discerned that there were two types of adrenergic receptor, which he termed alpha and beta. He was also an ardent skeptic of the existence of receptors as physical entities. In addressing the question of whether it might be possible to learn more about alpha and beta receptors by purifying them from tissues to study their properties in isolation, Ahlquist had written that such studies would only be worthwhile “if I was so presumptuous as to believe that alpha and beta receptors really did exist. There are those that think so and even propose to describe their intimate structure. To me they are an abstract concept conceived to explain observed responses of tissues produced by chemicals of various structure.”

> I introduced myself and immediately started into an energetic lecture about receptor theory. There were fifteen students in the class and from my first word they were all scribbling furiously in their notebooks, so I was impressed with their level of attentiveness. After five minutes, though, one of the students raised his hand. “Excuse me, Dr. Lefkowitz, but I think you’re in the wrong room. This class is Biochemistry 101 and the students are taking an exam. I know because I’m the proctor.”

> How had it come to this? My lab had spent fifteen years, starting from scratch, systematically developing every procedure that would be necessary to purify the receptors and set up the ultimate elucidation of the gene sequence. We had developed radioactive ligands to track the receptors and cutting-edge techniques to purify the receptors. The idea that some other group was now going to beat us in becoming the first to learn what the receptors actually looked like was galling. Adding further salt to this wound was the fact that Ross and colleagues were beating us using all of the procedures that we had developed and published.

> Venter jokingly credited me with his subsequent success. As he told it, for a period of fifteen years his lab had competed with mine and been scooped by us at every significant point. The cloning of the beta receptor gene was for him the last straw, and he realized he needed to find a different line of work. After losing this race, he became interested in developing technologies to sequence DNA more quickly, and ultimately decided to sequence the human genome.

> Everywhere I went on campus, my colleagues would ask, “How is the sequencing going? What does the receptor look like?” My answer was always the same. “This receptor isn’t going to look like anything. It’s the first receptor of its type to be identified, so it’s going to look completely unique.” As the sequence came into focus, however, I realized that I was spectacularly wrong. The beta-2 adrenergic receptor did look like something else: specifically, it looked like rhodopsin, a light-sensitive protein found in the eye. The primary sequence identity between the beta-2 receptor and rhodopsin was not very high and confined to just one region, but both had seven predicted transmembrane regions and they were clearly related

> “How was it?” Brian asked. I wanted to be encouraging, but I also didn’t want to lie to him. I put my arm around him and leaned in. “Brian,” I said, “That was the best talk you could have given.” Brian smiled. This line would become a running joke between us for years to come.

> Teach trainees to build their careers around problems, not techniques. Sometimes trainees learn a new technique and then spend the next few months or years, or in some cases their entire careers, looking for other problems to which they can apply their newly learned technique over and over again. This is exactly the wrong approach for developing a career in science

> When the slides were ready, I would give a series of practice talks, sometimes by myself and sometimes in front of small groups of trainees from my lab. The hard work on the slides and practice talks prepared me well for my renewal presentations. However, these efforts also served another purpose: they showed my trainees how hard I was working to make my presentations shine. The unspoken message was that I also expected my trainees to work hard on their presentations… (mehr)