Thursday, July 29, 2004

Immodest Francis Crick--Theoretic Biologist


(While writing my version of Crick’s obituary, I received an e-mail from Janice informing me that Francis Crick succumbed to colon cancer--the was originally written in 2004)

“I have never seen Francis Crick (see photo) in a modest mood.” So James Watson began his story of Double Helix.  And Crick had every reason not to be in that mood.  Janice, I bet it was quite a surprise when his grand-daughter told you that “He is my grand-father!” at Harvard computer room some years ago.)  Reading about him for so many years, I feel like I knew him by heart.

“It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”--Letter to the Nature (April 25, 1953). Almost every molecular biology professor put this passage in the lecture notes.  This was a compromised statement between Watson and Crick who was 12 years senior to Watson.  The aggressive, quick-witted Crick wanted to elaborate the detailed copying mechanism on the original article of April 25, 1953 (Molecular structure of nucleic acids), the younger, but more cautious Watson was afraid if their hypothesis of copying mechanism were not quite true, it might ruin the whole thing.  They quickly wrote the follow up article (Genetic implications of the structure of deoxyribonucleic acid) that showed up on May 30, 1953 issue of Nature.  It has turned out Crick was correct in the first place.


Sydney Brenner once said Crick was the only one he knew that can make a living by being a theoretic biologist (Crick was working on the PhD in physics when WWII broke out, he then worked on the magnetic and acoustic mine in the British Admiralty.)  After moving to Salk Institute, Crick devoted his life in ‘the scientific search for the soul’ (this is the subtitle of his book Astonishing Hypothesis)—hypothetic neuroscience.

When Watson and Crick constructed that famous DNA model in April 1953, Sidney Brenner (originally from South Africa, born of Jewish parents) was in Oxford University and went to Cambridge to see it.  Brenner and Crick were also together in the Woods Hole Lab and Cold Spring Harbor Lab (in Long Island) in 1954.  Brenner joined Crick at Cavendish Lab in 1956 and “spent 20 years sharing an office with Francis Crick.”  Crick moved to Salk Institute at La Jolla, in 1976 and Brenner rejoined him there again in 2001. Brenner began to work on the ‘elegant’ C. elegans in late 1950s and for which he just received the Nobel Prize (programmed cell death or apoptosis) in Medicine in 2002—exactly 40 years after Watson and Crick did.  Brenner’s Nobel Lecture, Nature’s Gift to Science, talking about the importance of choosing the model organism for the intended research.

It is now almost a ‘common knowledge’ that how DNA uses its four bases to pass along the ‘secrets of life’ to the making of proteins.  It was Crick that first proposed his ‘adaptor’ tRNA (transfer RNA) hypothesis.  It was actually never published; it was just a letter to the then so-called RNA Tie Club. He also worked with Vernon Ingram (who discovered the replacement of Glu by Val at 6th position of β-globin chain in sickle cell HbS, as predicted by Linus Pauline) and Sydney Brenner in this field.  Brenner was twice a visiting professor at Harvard, as was Crick.

“Crick is very different: brighter than Watson, but he talks a lot, and so he talks a lot of nonsense.” This was from Erwin Chargaff whose discovery of ‘A = T’ and ‘C = G’, along with Rosalind Franklin and Maurice Wilkin’s X-ray crystography of DNA (see photo) were the most important hints to Watson & Crick, in my view.  I have read many reports that Chargaff had a lot of resentments (hence sour grape) that he was ‘so close’ and yet he let the ‘glory’ slip away. He was one of the 20 members of RNA Tie Club.  By the way, Chargaff was another Jew who fled Hitler’s Nazi. (my favorite topic that I mentioned in summer reading.2_2004)

It took many years before the DNA structure hypothesis was firmly accepted.  Matthew Meselson’s semiconservative replication provided the first confirmation.  Meselson took his Ph.D. from Linus Pauling at Cal Tech and who got an honorary degree at Joy’s graduation at Northwestern in 2003.

A few years ago, Time published 100 most influential people of the last century; both Watson and Crick are on the list.  Watson gave an introductory talk on the 2001 Nobel Symposia (Beyond genes) in Sweden, and Crick was no where in sight.  Throughout 2003 there were numerous activities celebrating the 50th anniversary of the discovery of DNA structure.  Watson savored the glories on many functions, and Crick none.  He was not in his best health then, but that was not the main reason.  He preferred to read and think and hypothesize his science.