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Saturday, February 23, 2013

From a Molecule to A Cure

Just to be fair, I want to talk about someone who worked on single target - single drug treatments. This person did her work in a manner that had some "wealth in the system". This was not my experience but I can appreciate that it can be done. I went to a speech given by Gertrude Belle Elion a few years before she died. She won the Nobel Prize in Medicine in 1988. Of all the seminars I attended, this one has stuck with me. At the end of her talk she was asked by one of our professors if she would have benefitted from the modern tools of biotechnology. I can't remember her exact response but her answer was NO! She made it clear that research was something that requires the human mind, not just applying a few technologies. She showed a map of discovery. It went from chemistry to microbiology to biochemistry with stops through physics and math. The process she described was similar to Feynmans view of science. The stuff our professors hoped we had picked up during our education under their watch.

12 December 2008 , published , doi: 10.1098/rsbm.2007.0051 54 2008 Biogr. Mems Fell. R. Soc. 

After receiving her bachelor’s degree in chemistry from 
Hunter College in 1937, Trudy realized that neither she nor her family had enough money for 
her to attend graduate school. She began to look for a job, and immediately ran into the prover- 
bial brick wall. ‘Nobody … took me seriously. They wondered why in the world I wanted to 
be a chemist when no women were doing that. The world was not waiting for me.’ Secretarial 
school followed, and then teaching at a hospital and a high school. She finally landed a posi- 
tion, albeit nonpaying, with a chemist, just to keep busy in her field; during this period she 
decided to pursue her master-of-science degree, which she received in 1941 from New York 
University. During her graduate studies, she started teaching high school chemistry and physics 
as a ‘permanent substitute’ for $7.50 a day. 
Her big break came when the United States entered World War II. Since there were few men 
around, women came to be seen as potential employees, and Trudy was hired as an analytical 
chemist; her job included the measurement of the acidity of pickles and the colour of mayon- 
naise. After a while she tired of those functions and a spell of testing the tensile strength of 
sutures, and sought more meaningful work. The most interesting opening was at Burroughs 
Wellcome, where biochemist George Hitchings (ForMemRS 1974) was trying to make antago- 
nists to nucleic acid derivatives. Hitchings, who would later become a member of the National 
Academy of Sciences, ‘talked about purines and pyrimidines, which I must confess I’d never 
even heard of up to that point, and it was really to attack a whole variety of diseases by interfer- 
ing with DNA synthesis. This sounded very exciting.’ She accepted the position of biochemist 
in 1944 and spent the next 39 years at Burroughs Wellcome, becoming head of the Department 
of Experimental Therapy in 1967. 
Let Trudy explain how she started out making compounds and ended up eventually with the 
first effective drug that induced remission in childhood leukaemia. 
At the beginning … it was my job to find out how to make (compounds). So I’d go to the library, 
look up the old literature to see if I could figure out how to do it. … I would just go ahead and 
make the compounds, and then the question was, well what do we do with these compounds? 
How do we find out if they really do anything?

She attracted many associates who became known as 
a research dream team, some of whom invented azidothymidine (AZT), a mainstay drug for 
treatment of HIV (human immunodeficiency virus) infection. 

Trudy was awarded the Nobel Prize in physiology or medicine in 1988 for her discovery 
of important principles for drug treatment. 

What were those principles for drug treatment? Gertrude and George Hitchens demonstrated differences in nucleic acid metabolism between normal human cells, cancer cells, protozoa, bacteria and virus. On the basis of these differences they developed drugs that blocked nucleic acid synthesis in cancer cells and noxious organisms without damaging the normal human cells.

How does the biotech/pharma industry hire people? How do they use the new buzz word search technology to sort through resumes and end up with someone like Gertrude? Someone who can use the literature to make the molecules AND "find out if they really do anything?"

The executives may be concerned about whether or not they can find these people in the future. Gertrude came from the secretarial pool. She was a substitute high school teacher. Would Gertrude Elion have succeeded, sans PhD as she was, at Pfizer or Merck? What did she have that so many are missing today? What did she and George Hitchens do that the drug developers are not doing today? With all of our modern technology we are missing something. 


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