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Many medicines started as a plant extract that someone tweaked until it worked. Gertrude Elion and George Hitchings tried something different: understand how a cell makes DNA, then design a molecule that jams that process. This post explains their idea, works through the chemistry of one of her drugs, and tells how she got there without a doctorate.
Who was Gertrude Elion?
The Nobel Prize summary records that she was born in New York on 23 January 1918 and died on 21 February 1999. In her Nobel autobiography she writes that her grandfather died of cancer when she was 15, which made her want to do work that might lead to a cure.
She entered Hunter College in 1933 and majored in chemistry. As a woman she struggled to find a job as a chemist, so she taught chemistry, physics and general science in New York schools for two years while doing research at night and on weekends at New York University. She earned a master's degree in 1941. When the Second World War created a shortage of chemists, she found laboratory work, first in food quality control, and then joined George Hitchings at the Burroughs Wellcome laboratories.
She began a PhD at night at Brooklyn Polytechnic Institute, but was told she could not continue part-time. She chose, in her words, "to stay with my job and give up the pursuit of a doctorate."
What did "rational" drug design mean?
The 1988 Nobel press release explains that drug development had mainly relied on chemically modifying natural products. Elion and Hitchings, who worked together from 1945, took "a more rational approach based on the understanding of basic biochemical and physiological processes".
Their starting point: cells need purines (adenine, guanine and related bases) and pyrimidines to make nucleic acids. Cancer cells, bacteria, protozoa and viruses use these pathways differently from normal human cells. A molecule that looks like a natural base but does not behave like one, an antimetabolite, can block DNA synthesis where those differences are greatest.
How does a purine look-alike work? A chemistry example
Compare hypoxanthine, a natural purine, with 6-mercaptopurine (6-MP), one of the first drugs from the work. PubChem gives their formulas:
Hypoxanthine: C5H4N4O
6-Mercaptopurine: C5H4N4S
The only change is that the oxygen at position 6 of the purine ring is replaced by sulfur. Work out the molar masses with C = 12.011, H = 1.008, N = 14.007, O = 15.999 and S = 32.06:
Shared part, C5H4N4. 5 × 12.011 + 4 × 1.008 + 4 × 14.007 = 60.055 + 4.032 + 56.028 = 120.115 g/mol.
Hypoxanthine. 120.115 + 15.999 = 136.11 g/mol.
6-MP. 120.115 + 32.06 = 152.18 g/mol.
Both match PubChem. One atom swap gives a molecule close enough in shape for the cell's enzymes to take it up, but different enough to disrupt the pathway.
A second case is allopurinol, also C5H4N4O, an isomer of hypoxanthine. The ring atoms are rearranged. The press release explains that it blocks xanthine oxidase, the enzyme involved in making uric acid, which is why it treats gout.
Common mistakes:
Confusing purines and pyrimidines. Purines (adenine, guanine) have two fused rings; pyrimidines (cytosine, thymine, uracil) have one.
Assuming same formula means same molecule. Hypoxanthine and allopurinol share a formula but are different compounds.
Rounding too early. Keep three decimals until the final step.
The chemical constitution of DNA and RNA is listed in the NEET (UG) 2026 syllabus. Our guide to biomolecules in chemistry covers the bases in more detail.
Which drugs came from the work?
The press release lists:
1950–51: thioguanine and 6-mercaptopurine against leukaemia, and pyrimethamine against malaria.
1957: azathioprine, which prevents rejection of transplanted organs.
1963: allopurinol for gout.
1977: acyclovir, described by Elion and co-workers, the first effective drug against herpes virus infections.
The press release adds that AZT, an early AIDS drug, was described in 1985 by other scientists at the same institute, building on the same ideas. A 1989 Science paper by Elion, "The purine path to chemotherapy", summarises the line of work.
Elion headed the Department of Experimental Therapy from 1967 until she retired in 1983. She shared the 1988 Nobel Prize in Physiology or Medicine with Hitchings and Sir James Black "for their discoveries of important principles for drug treatment".
What can a student take from Elion's way of working?
Learn the mechanism, not just the facts. Knowing how cells make DNA let her predict what would block it.
Cross subject lines. She wrote that she moved from organic chemistry into biochemistry, pharmacology, immunology and virology.
Keep going when the usual path closes. No doctorate did not stop her doing first-rate research.
Molar mass and formula questions reward a careful, repeatable method. The Fermi Problem Library has a step-by-step solver that explains the reasoning, so you can check where your working went wrong.
Try it now: look up guanine and thioguanine on PubChem and calculate how much heavier the drug is than the natural base.
