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Monday, November 28, 2011

Marmite and nuclear fallout

Marmite and nuclear fallout

Sir Peter Medawar, Nobel Laureate in immunology and philosopher of science once wrote: “If politics is the art of the possible, then science is the art of the soluble”. The great trick in science is to manipulate the experimental conditions in such a way that the potential solution becomes accessible. Today, I will document two examples of discovery in nutritional science showing indeed the ingenuity of the mode of discovery but also the happenstance of scientific discovery. Lets begin with the ingenuity.

Atmospheric carbon dioxide is comprised predominantly by the stable form of carbon, designated 12C. Radioactive carbon is a heavier for designated 14C. Above ground nuclear testing began in 1955 and continued until a limited nuclear test ban treaty came into effect in 1963. During this period, atmospheric CO2 became more enriched with 14C than normal and when the ban was enacted, those levels plummeted, not because of the decay of the radioactivity (14 carbon has a half life of 5,700 years) but because this CO2 was absorbed into the earths biomass. Ultimately, everything we eat comes from this biomass so we were exposed and thus enriched ourselves in the radioactive form of carbon (14C) but at miniscule levels of no biological hazard. Even though the amounts in us are trace, smart physicists can measure the ratio of 14C to 12C. If a cell is created during the period when 14C is high then we can track the life cycle of such cells by seeing how soon the ratio of the radioactive form to the normal form returns to pre-nuclear testing levels. A fast return means that the cell has a short half-life. A slow return means that the cell has a long half-life. By recruiting people born before, during and after the above ground nuclear tests and following them over time, a group of scientists at the Karolinska Institute (Nature October 6th 2011) were able to show that fat cells have a life of about 10 years and the fat within that cell is renewed 6 times during this period. That means that the fat within the cell has a life of about 1.6 years. The same group using this technique also showed that in fat people, the life of a fat cell is shorter and also that when people diet, the number of fat cells remains constant. The data are extremely useful I understanding the dynamics of fat metabolism over decades and surely, this bunch of smart Swedes must get recognition for their “art of the soluble”.

 Let us now turn to happenstance in scientific discovery. Justus von Liebig (1803 - 1873) is generally regarded as the father of food chemistry. Like many of the leading academics of today, he was an entrepreneur. Together with a Belgian scientist, George Giebert, he developed a means of concentrating beef into a nourishing beef extract. Because European beef was expensive, he located his manufacturing plant in South America.  The Liebig Extract of Meat Company traded as Lemco and after his death, the product evolved into Oxo, a beef extract now owned by Unilever. Liebig also turned his technological know how to brewer’s yeast, managing again to manufacture a nutritious concentrate. Ultimately, a British company, The Marmite Food Extract Company, would manufacture this extract and sell it as the Marmite we know today. Incidentally, Unilever also now own the Marmite brand. Marmite has a special place in the history of nutrition with very significant links to major public health issues of today.

That story starts in the slums of Bombay, as it was known then, and a rampant form of anaemia, common among female workers in the textile factories. A young British medical doctor specialising in clinical chemistry, Lucy Wills, was persuaded to take up this challenge. She began by ruling out infection and infestation and ascertained that the form of anaemia was macrocytic anaemia, an inadequate number of red blood cells. She then turned her attention to the diet of these poor women and using monkeys as experimental models was able to induce this form of anaemia in the monkeys by feeding the bland and rice dominated diets eaten by the women. Vitamin A and Vitamin C had just been discovered and she quickly ruled them out as causative factors.

Now ex-pats love a bit of home comfort and Marmite was as British as these comforts come. One can imagine Dr Wills sitting in her lab among cages of monkeys, one of whom would somehow charm her to become her little pet. And it’s not impossible to imagine that she would let this particular monkey share a bit of Marmite at lunchtime. But it is difficult to imagine her utter shock and surprise when alone among the anemic monkeys, this one recovered.  However, from this unplanned experiment of n = 1, she simply moved directly to her patients and gave them Marmite. Their anaemia was cured. It was 1941 before Roger Williams of the University of Texas identified folic acid as the active vitamin in green leafy vegetables that cured macrocytic anaemia (folium is the Latin for leaf). Two years later, at Lederle Pharmaceutical (now part of Pfizer) from one and a half tons of liver, folic acid crystals were isolated and the first synthetic folate was made.

Ethical approval for mass exposure to miniscule levels of ionising radiation is unthinkable but the super nuclear powers don’t need ethical approval to detonate atomic bombs above ground. And, ethical approval for a clinical trial based on an unplanned experiment with one monkey is also unthinkable. Science moves in odd ways.

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