Alex Rich on Working on RNA Structure with Jim Watson
  Alex Rich     Biography    
Recorded: 20 Aug 2006

Jim had returned to resume his fellowship with Max Delbrück . And I ah, I had met Jim actually when I arrived in 1949. He was then just leaving to go to work with Herman Kalckar. What interested me at that point, was what about RNA? Not much was known about RNA, and in fact if you look at the reviews of that period, many people wondered whether RNA was a linear polymer at all because it has the potential for branching at the two-prong and three-prong hydroxyls. By the end of this conference I was determined to see whether RNA could form a double helix. Now in the paper by Jim and Francis they pointed out explicitly that ribose could not form that structure because of the van der Waals intrusion of that two-prong hydroxyls. And ah, so it wasn’t clear. Jim became quite interested in that question as well, and we decided to work together. He was perhaps somewhat less interested in doing phage work in the Delbrück lab. So he used to come over quite often to Crellin, the chemistry lab. And what we did is we wrote to a number of people, asked them to send us preparations of RNA, and then tried to draw fibers using that same method. Gradually it became possible to accumulate pictures of fibers of RNA somewhat oriented, not as highly oriented as the DNA fibers. But they were always fuzzy and peculiarly most of them looked the same. The diffraction pattern was the same. Even though we knew that the base ratios were no longer one to one. They varied all over the map, in different preparations. And yet you pull a fiber, out came the same pattern. Whether it was a double helix or not we could not tell. Jim and I published a couple of papers during ’54. One in Nature and one in the Proceedings, PNAS. But basically there was no resolution. We could not decide, we pointed out that there were some puzzles. Because even though the base ratios varied all over the place the patterns looked the same. So there was something there that we didn’t understand.

MP: So I just want to ask you. At that time, RNA was an open question. So when you started working…when you just questioned yourself could the molecule even to form any kind of double helix, or what is that, why did you turn to RNA?

AR: Well we knew at the time that RNA was found in viruses. And it was known that the viruses could be changed, and it seemed reasonable to believe that the RNA played a role for carry the information for replicating viruses. But if so how did it do it? The way, the model that we had for DNA, namely replication by separating complementary strands, that seemed quite reasonable. But could RNA do that or not, we just didn’t know.

Alexander Rich (b. 1924), biologist and biophysicist, is the William Thompson Sedgwick Professor of Biophysics and Biochemistry, at the Massachusetts Institute of Technology, Department of Biology. Rich first joined the MIT faculty in 1958. Subsequent to serving in the U.S. Navy from 1943-1946, Rich earned his undergraduate degree (A.B., magna cum laude, 1947) and medical degree (M.D., cum laude, 1949) from Harvard University. While doing his postdoctoral work at Caltech under Linus Pauling, Rich met Jim Watson and they began their collaboration on the structure of RNA. From 1969-1980 he was an investigator in NASA's Viking Mission to Mars, the project which designed experiments to determine if there is life on Mars.

Alex Rich's most well-known scientific discoveries are left-handed DNA, or Z-DNA, and the three-dimensional structure of transfer RNA. He has been elected to the the National Academy of Sciences (1970), the American Academy of Arts and Sciences, the Institute of Medicine, the French Academy of Sciences, the Russian Academy of Sciences, and the Pontifical Academy of Sciences (the Vatican.) Among other awards and honorary degrees he has received are the Medal of Science granted by President Clinton in 1995, the Rosentiel Award in Basic Biomedical Research, and the Presidential Award of the New York Academy of Sciences.

Since the 1980s Alex Rich has been actively involved in number of companies in the pharmaceutical and biotechnology industries. He co-founded the pharmaceutical company Alkermes Inc. in 1987 and currently serves as a director. He is also Co-Chairman of the Board of Directors of Repligen Corporation, Inc., a biopharmaceutical company, a member of the Scientific Advisory Board of Roseta Genomics, and a member of the Board of Directors for Profectus Biosciences, Inc.