On this page
By the late 1960s, the Nobel committee notes, chloroquine and quinine were working less and less well and malaria was on the rise. One of the answers came from a researcher in Beijing reading medical texts more than 1,500 years old. Tu Youyou's discovery of artemisinin is a story about patient screening, a failed result, and the question that fixed it: what if the method, not the plant, is the problem? This post traces what her team did, works through a short chemistry check on the molecule, and draws out what students can learn from her approach.
What was the Nobel Prize for?
The 2015 Nobel Prize in Physiology or Medicine was split: one half to William Campbell and Satoshi Ōmura for a therapy against roundworm parasites, and the other half to Tu Youyou "for her discoveries concerning a novel therapy against Malaria". The press release says artemisinin "has significantly reduced the mortality rates for patients suffering from Malaria", a disease it described as claiming more than 450,000 lives a year at the time.
What was Project 523?
In her Nobel lecture, Tu explains that China set up a national antimalarial programme, called the 523 Office after its start date of 23 May 1967. Several thousand compounds were screened between 1967 and 1969 without finding an effective drug. Elsewhere, she notes, the Walter Reed Army Institute of Research in the United States had screened over 214,000 compounds by 1972, also without a breakthrough.
In 1969 Tu was appointed to lead a Project 523 group at the Institute of Chinese Materia Medica in Beijing. Within three months she had gathered over 2,000 herbal, animal and mineral prescriptions from old texts, folk recipes and interviews with practitioners, and narrowed them to 640.
Why did the first extracts fail?
The plant qinghao, *Artemisia annua* or sweet wormwood, stood out because it appeared in several hundred recipes. But, as the Nobel committee's scientific background explains, extracts gave inconsistent results, from 12 to 40% inhibition of malaria parasites in mice.
So Tu went back to the literature. In a recipe by Ge Hong, from his *Handbook of Prescriptions for Emergencies* written in the fourth century, she found a description of obtaining "juice" from the leaves using cold water instead of the usual boiling. That suggested heating might be the problem. She switched to a low-temperature extraction with ether instead of the ethanol used before.
What happened with sample 191?
In the lecture, Tu describes the turning point. On 4 October 1971, sample No. 191, the neutral portion of the qinghao ether extract, was 100% effective against rodent malaria when given orally at 1.0 g/kg for three consecutive days. Monkeys infected with malaria showed the same result between December 1971 and January 1972.
The first clinical trial ran from August to October 1972, on 21 patients in Hainan province and 9 at a Beijing hospital. The active compound was isolated in November 1972 and later named artemisinin, or qinghaosu.
Worked example: a chemistry check on artemisinin
Tu's collaborators determined the formula C₁₅H₂₂O₅ in April 1973, and X-ray crystallography later showed it was a sesquiterpene lactone with a peroxy group. Two quick calculations from the formula are worth doing.
Molar mass. Using C = 12.011, H = 1.008, O = 15.999 g/mol:
Carbon: 15 × 12.011 = 180.165
Hydrogen: 22 × 1.008 = 22.176
Oxygen: 5 × 15.999 = 79.995
Total: 282.34 g/mol
Oxygen makes up 79.995 ÷ 282.34 = 28.3% of the mass.
Degree of unsaturation. For CₐHᵦOₓ, the number of rings plus π bonds is (2a + 2 − b) ÷ 2, and oxygen does not change it. For C₁₅H₂₂O₅: (30 + 2 − 22) ÷ 2 = 10 ÷ 2 = 5. Artemisinin's structure fits: PubChem lists it as tetracyclic, so four rings, one of them carrying the O–O peroxide bridge, plus one C=O in the lactone. This is the same calculation that JEE organic chemistry asks you to do on unknown formulae.
What came after?
Tu's institute received a new drug certificate for artemisinin in 1986 and for dihydroartemisinin in 1992. Today artemisinin is used in combination therapies, and in her lecture Tu quotes the World Health Organization's warning that resistance emerging in the Greater Mekong subregion is "a matter of great concern".
What can a student take from Tu Youyou's way of working?
Search widely, then narrow. Two thousand recipes became 640, then one plant.
Treat inconsistent data as information. A 12 to 40% spread pointed to a method problem.
Read old sources critically. Ge Hong's text gave a clue about method, which she then tested properly in animals and patients.
Share findings. Her lecture shows letters from other institutes asking for her results, which her team answered.
A failed experiment is often the most useful one, a point we make in our post on why mistakes help learning.
If functional groups or unsaturation are shaky, the Fermi Concept Library covers every concept in physics, chemistry, biology, mathematics and computing, so you can revise one idea at a time.
Try it now: work out the degree of unsaturation for C₁₀H₁₆ and C₆H₆, and sketch one structure that fits each.
