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Lawrence Bogorad, Maria Moors Cabot Professor of Biology Emeritus, Chair at Harvard University, and Member of The National Academy of Sciences

I think of major career decisions in two classes: the first is choosing research problems and the second is electing sites of employment.

I have had only two permanent jobs, both at universities. I have had no reason to regret either choice. I don't know how, but I managed to avoid bad working situations. So much for what I know about choices of employment sites.

What about choices of research problems? I spent two years in Sam Granick's laboratory at the (then) Rockefeller Institute for Medical Research as a postdoctoral fellow. He was trying to find the biosynthetic pathway to chlorophyll by generating, isolating, and characterizing mutants of Chlorella vulgaris that had blocks in chlorophyll formation. I joined the effort. I learned a lot about microbiology, porphyrins, and chloroplasts from and with Sam Granick. For a young person starting in science it was important that this apprenticeship was in the atmosphere at the Rockefeller. Almost 50 years ago, it was a relatively small place with an extraordinary group of cell biologists, geneticists, microbiologists, biochemists, medical researchers, etc. Contacts among many of these biologists were frequent, informal, and often close. All of the scientists at the Institute sat down together for lunch in the same dining room every day. I found the atmosphere welcoming and the opportunities for learning through questions, listening, and discussion enormous and exciting. The value of face-to-face and thought-to-thought interactions with enthusiastic critical scientists was inestimable. Above all, I was lucky to have Sam Granick as a gentle, wise, and critical mentor.

At the beginning of the second year that I was with Sam Granick we tried our totally inexperienced hands at enzymology. We found that extracts of C. vulgaris could catalyze the formation of biologically interesting tetrapyrroles from the monopyrrole porphobilinogen. We crystallized porphobilinogen from the urine of acute porphyria patients at a few New York City hospitals.

Near the completion of my postdoctoral fellowship I had two job offers. One was at the Rockefeller as an Assistant (equivalent in rank to an Assistant Professor at a university) in Sam Granick's lab. The second was an Assistant Professorship in the Department of Botany at the University of Chicago, where I had been an undergraduate, a graduate student, and an Instructor (an ancient, honorable, and extinct rank in most institutions). The Rockefeller position would provide full time for research and, at that time, all research funds. I would be part of Sam Granick's research group. But I was young, impatient, and confident. Also, even with a low salary we could live in New York City (across the street from the lab) while our children were very young, but we could see that, as our children grew up and started school, we would have to move out of the neighborhood. Moving away meant commuting, which would make it hard to get back to the lab at night. I chose to go to the University of Chicago. I doubted that I had made the best choice as I was trying to get started alone and with almost no research funds or equipment while facing a large teaching obligation. A few months after I got to Chicago I wrote to Sam Granick asking if his offer was still open. About a week later I embarrassedly withdrew my inquiry because I realized that I placed a very high value on independence. I will never know if I made the best choice for me. The experiment could not be repeated.

At the University of Chicago, I continued studying tetrapyrrole biosynthesis. Two enzymes involved in the biosynthesis of uroporphyrinogen III were identified. I developed an increasing interest in chloroplasts, got involved in a few plant physiological problems with my colleague Wayne McIlrath, and my interest in porphyrins led to curiosity and work on bile pigments, phycobiliproteins, complementary chromatic adaptation, red algae (Cyanidium caldarium), and cyanobacteria. In the early 1960s, in a wonderful collaboration with Hewson Swift fueledas is often the caseby graduate students, we turned to studying chloroplast nucleic acidsribosomes, RNA, and DNA. This led to studying chloroplast RNA polymerase activityduring greening of leaves of etiolated maize seedlings. At this time I was enjoying teaching, as always, but teaching three courses a year (two of them with laboratories) was a wearing obligation.

The most attractive invitation came from Harvard. I found that the research and office facilities of Harvard faculty members were much more comfortable than what I had at Chicago. I expected that the undergraduate and graduate students at Chicago and Harvard would be comparable. My teaching obligations would be more reasonable and modest research support would be available. Furthermore, the invitation came for a time that would be minimally disruptive for the others in the family. I could find little against moving. So, why not!

A major career decision of the "kind of research" type was to stop working on porphyrin biosynthesis. Other interesting and exciting projects were claiming ever more attention, whereas working out the details of the enzymatic synthesis of uroporphyrinogen III would require analytical tools of a sensitivity that did not exist at the time, or a level of skill as a synthetic organic chemist far beyond mine, or both. I was not prepared to become a synthetic organic chemist and I did not know how to improve the analytical tools. Walking away from an active love affair is not easyeven if the beloved requires more care and understanding than you can give.

One of the newer things claiming attention (around 1970) was the genetics of Chlamydomonas chloroplast ribosomes. In the 1960s and early 1970s, it seemed possible that chloroplasts might be autonomous and contain the same complement of genes as their presumed cyanobacterial ancestors. However, we found that genes for some components of Chlamydomonas chloroplast ribosomes were nuclear, whereas other genes were plastidic. These data led to the realization that genes had either been transferred from the endosymbiont-plastid genome to the nucleus and/or that the products of nuclear genes had come to be substituted for products of endosymbiont-derived genes (Bogorad, 1975). In the early 1970s, we were continuing to study maize chloroplast RNA polymerase, and DNA cloning technologies that were being developed offered the possibility of being able to provide cloned chloroplast genes as templates for in vitro experiments. In 1976, we made a restriction map of the maize chloroplast chromosome, and mapped the ribosomal DNAs on it. During the next few years we mapped, identified, cloned, and sequenced chloroplast genes that could be used as templates for RNA polymerase research. In the early 1980s, the expression of regions of the entire maize chloroplast chromosome and of specific genes in relation to illumination of dark-grown seedlings was an obvious direction for the research (now known as functional genomics). And so on. I have not regretted the choice of this research route.

Only the space limitation imposed by the editor prevents me from listing, let alone describing, other interesting, challenging, and exciting lines we followed simultaneously and the names of coworkers in all the efforts in which I have engaged.

I was fortunate in finding the University of Chicago and Harvard to be intellectually stimulating, exciting, and hospitable places for me. With the indispensable help of funding agencies it was possible to work with wonderful, smart, inquisitive, and dedicated students, postdocs, and visiting senior scientists over a period of many years on a number of different kinds of research problems in physiology, biochemistry, and molecular biology. Being able to get all of these people to come and teach me things has been, in retrospect, more than I had expected from a career in science. Arguably, my worst career error was to be born too early! I will miss the next exciting chapter in biology. This one has been wonderful to behold!