Wednesday 30 December 2015

Project 523

Never 'eard of 'er!  How many times have you heard someone rabbiting on about a famous woman of science and that's your response? Then again, ask most people if they've heard of Professor Aragorn, inventor of mithril silver and half of them will say Never 'eard of 'im! and the others will acknowledge his contribution as they quaff a foaming mug of ale with Tom Bombadill. I was caught with ignorance-pants on my head when Tu Youyou 屠呦呦 [R mentoring a younger woman-in-science - you can tell they are scientists because both are wearing white coats] won the 2015 Nobel Prize for Phys&Med shared with William "Irish" Campbell and Satoshi Ōmura. Never 'eard of 'er indeed. She's foreign, she's female and her research was carried out behind the bamboo curtain, so it's not the kind of copy chewed over by popular science. Well, it's her 85th birthday today, so we may have a look at her achievements.

In the mid-1960s at the height of the Vietnam War, malaria was a serious drain on the Effectives of both sides of the conflict. A soldier can hardly walk, let alone point a gun in the right direction, if he's weaving about with a fever and headache and the shakes. The original useful prophylactic against malaria, as far as Western medicine was concerned, was quinine aka Jesuit's Bark an extract from the bark of Cinchona officinalis a South American tree. A synthetic alternative was developed at Bayer in 1934 and eventually called chloroquin [structure L]. But 30 years later, a lot of malarial strains were resistant to quinine and chloroquin; and the race was on to develop effective alternatives.  The US military threw down the challenge to pharmaceutical companies: the prize being a lucrative government contract.  The besieged, bombed, defoliated and impoverished North Vietnamese didn't have such access to megaPharm and wouldn't have been able to afford the drugs aNNyway. They asked for help from their idealogical mentors North of the border in the People's Republic of China. hmmm not very fertile ground on the face of it, because the PRC was in the turmoil of the Cultural Revolution and intellectuals of all sorts were suspect: publicly humiliated, losing their jobs, shipped out to be a good peasant in the country, or executed. Science itself was suspected for being bad for progress towards a Maoist paradise of happy workers and peasants in identical suits of blue cotton. The Chinese VP Chou En Lai realised that malaria was a scourge not only for N.Viet soldiers trudging through the foreign jungle, but for millions of peasants and soldiers across the border in Southern China where malaria was also endemic.

On 23rd May 1967, a cadre of 600 scientists, soldiers and others was brought together at a top-secret "Project 523"and given the task of finding an antidote for malaria. Tu Youyou had been trained as a pharmacologist and spent two years of testing thousands of compounds for a) activity against the malaria parasite, as well as b) very limited toxicity and side-effects in humans. She also had a deep academic interest in traditional herbal medicine and after so many dead-ends decided to go back to The Ancients and see what they had to say on the matter.  Like Anglo-Saxon healers discovering an effective cure for eye-infections, the Chinese had a long history of tinctures and extracts from plants to cure disease or ameliorate symptoms.
Tu went back to her books to identify plants that had promising properties and narrowed down the search to Artemisia annua - sweet wormwood - and some of the phenolics [like Artemisinin L] that her team purified from the plant. Her initial researches, and close reading of ancient texts, concluded that the active principal was heat-labile and so required a cold solvent [ether, hexane] extraction of the plant material. It proved singularly effective against malaria in mice and monkeys and so Tu Youyou decided, like Barry Marshall and JBS Haldane before her, to chug some down to see if it killed humans. It didn't kill her, and so a full scale clinical trial was implemented. It's not a great anti-malarial because the side-effects are not-so-good and it's hard to deliver it cheaply to millions of people but it was better than nothing and may have shifted the balance of power in the Vietnam war. It certainly improved the quality of life for Chinese people in regions where malaria still thrives. After her initial success she carried on doing reg'lar science in China invisible to the rest of the world.  Someone at the Lasker Foundation must have been doing their home-work because Lu Youyou was awarded a Lasker Prize in 2011 and people started to perk up and take notice of the achievements of this octogenarian from China. She is an icon for women in science because she exemplifies that, if you are sufficiently bright and creative AND are presented with a 'lucky' project, then you can make a significant break-through. It's not about academic quals: To Youyou is known as Professor Three Noes: No PhD; No Foreign Post-doc; No membership of the elite Chinese Academies. Yet she done good!

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