Banning food colours. Bad science ~ Bad legislation

Philippus Aureolus Theophrastus Bombastus von Hohenheim was born in 1493 and, perhaps not surprisingly, changed his name to Paracelsus. Celsus was a Roman physician who gave the element zinc its name and this pompous Swiss German medic decided to re-name himself  ‘Equal to Celsus’. He is famous for his dictat: ”Sola dosis facet venum”, which translates from the Latin into “The dose alone makes the poison”. In other words, everything is toxic at the right dose and under the right circumstances. Pure Alpine air is highly toxic if a certain dose is injected intravenously. The exact dose remains unknown since no such experiment has ever been done but you get my drift, I hope.

In 2007, a group of researchers from Southampton University published a paper in the prestigious medical journal, The Lancet, showing that a cocktail of food additives (6 colours and 1 preservative) caused hyperactivity and reduced cognitive function in children.  The study was well conducted. It used a placebo (identical in look and taste to the active cocktail) and it used a cross over design, meaning that each child received the active cocktail for a week and at another occasion the placebo for a week. They used two age groups, 3-year olds and a group of 8-9 year olds. The study was analysed by two important committees of experts, the UK Committee on Toxicology and the European Food Safety Authority (EFSA). Both gave their approval.

The consequence of this publication was very serious. The EU introduced a law mandating that a food containing any one of the 6 colours had to be labeled to state that the food contains a colour, which “may have an adverse effect on activity and attention in children”.  The findings were championed by the UK Food Standards Agency (FSA), which pushed for the ban. However, EFSA held the view that the effects of the food colourings on children's behaviour were small and the significance for children's development and education uncertain. The FSA view prevailed within the EU regulatory process and the ban came into effect.

Without doubt, this entire affair calls into question the entire approach that the EU and its agencies to the application of science to risk assessment. Lets just think about linking evidence to policy. No study has ever been completed in which any ONE of the 6 colours, on their own, had any effect on childhood attention deficiency.  Now one could respond to that and say that there may only have been one active colour so lets just label them all. But what about the 7^th additive used, the preservative, benzoic acid. That was excluded from the ban because it reduces the risk of food poisoning whereas colours are just colours. Now suppose the active ingredient was benzoic acid? There is a second flaw to the study, which is relative to the issue of dose as raised by Paracelsus. According to the authors in the paper, the doses were chosen because they represented normal exposure of children to food additives in UK children. Thus they used as their reference intake, the equivalent of three 56g bags of sweets for the younger children and double that for the older ones. Now 4 x 56 is 224 grams per day and at 4 calories per gram, that translates into almost 900 calories. This would mean that UK 8-9 year olds were deriving about 50% of their calories from sweets. That would quite simply lead to wholesale nutritional deficiencies since sweets are just pure sugar with some fat – no minerals or vitamins. Now, at the time this paper was written, the official UK data showed that in this age group, the contribution of all sugar confectionary was just 7%. How could they have got this dose so wrong? Why didn’t the FSA and EFSA not challenge the dose aspect of the paper?

In Ireland, we conduct food intake surveys for different age groups and what makes our approach unique is that we always collect the packaging of all foods consumed. These are photographed and the ingredients list entered on to a database. So we set out to ask if among teenagers and children, there was even one eating occasion among the 118,000 such occasions during the 7-day survey period, when all 7 additives were consumed. The answer was zero. In other words, no child or teenager in Ireland ever, even on just one occasion, consumed all 7 additives at the one time. We then went on to see if the levels of colours used in the Southampton study were ever achieved in our samples. Even at the top 1% of consumers of any colour, the intakes came nowhere near the levels used in the Lancet study.

The ban has come into force and most food producers have complied well ahead of the build up period. The public wasn’t screaming for this and the vast majority doesn’t even know it happened. But it satisfied the worried well who lobby the European Parliament and it was grist to the mill to their anti science approach to risk analysis. But some day the development of bad legislation based on bad science will come back to haunt them. 

Weight loss new year resolutions

Across the globe, millions of people will commit themselves to a New Year resolution to lose weight. Almost all will fail. The 5-year cure rate for obesity is less than the 5-year cure rate for the worst cancer, a view articulated by the American Medical Association’s Council on Scientific Affairs almost 25 years ago. If dieting were a drug, it would have failed the regulatory process given that it is generally not a long-term success. Yes, there are successes but they require life long adherence to a restricted food intake.  Basically speaking, when we gain weight and retain that gain for some time, it is recognised biologically as a new norm. When we lose weight, that same norm is constantly there and constantly wishing to re-establish itself. Losing weight is easy. It’s retaining that weight loss which is huge challenge. Rule number one in weight management: Whatever your weight is now, don’t gain any more. That is a battle you can win. 

There is a second battle you can win and that is to get fit and in so doing, you will negate all of the adverse effects of overweight and obesity.  There is a wealth of literature to show that it is better to be fit and fat than slim and sedentary. Physical activity will restore blood pressure to normal and will restore the ability of the body to handle glucose thereby reducing the likelihood of obesity-related diabetes. Physical activity enhances a sense of wellbeing, something that is readily lost when people gain weight. One of the very best teaching aids on the health benefits of physical activity is available at http://www.youtube.com/watch?v=aUaInS6HIGo.

Obesity and overweight remain among the major challenges to public health nutrition that we face today. The food industry and particularly the fast food industry are the focus of attention. And whilst food intake must be a part of the solution, so too must physical activity. The problem is that we have constructed a way of life that is sedentary and we have designed a built environment to support that. One of the most inspiring exponents of physical activity is Professor James Levine from the Mayo Clinic. He has championed the concept of NEAT: Non Exercise Activity Thermogenesis.   Basically, most of the energy we consume is dissipated as basal energy needs for the functioning of our heart, lungs, kidneys, brains and son on. We also dispose of some energy in digesting and absorbing food but this is minor. After basal activity comes exercise activity thermogenesis. This area of energy expenditure is planned as a walk, a game of golf, a jog, a swim and so forth. Levine has defined another activity (NEAT), which is effectively “fidgeting” or physical activity that is not seen as intentional physical activity: picking up the phone, walking to the bathroom, standing up to give a presentation. So, lying down at complete rest costs 5.4 kilojoules (Kj) per minute. That goes up to 5.6 if seated at complete rest. Sitting but “fidgeting” raises the figure to 8.2. Now lets take a look at the same activities while standing. Standing motionless has a cost of 6.1Kj.  Standing but fidgeting now increases the value to 10.3. Walking in a stop start fashion as in many work places raises the value to 13.7. Thus simple acts of physical activity make a huge difference to energy expenditure. Levine published a scientific paper in the very prestigious journal Science in which he overfed volunteers with an additional 1000 calories per day. Before the study and during the study, ALL volitional activities were controlled and minimized. He used advanced techniques to measure body fat (DEXA scans) and energy expenditure (stable isotopes). Having overfed these people for 8 weeks with an additional 1000 calories, all subjects gained weight. However, as I’ve explained before Blog of November 14^th last) , genetic variation will mean that some people will gain more weight than others. But in what fraction of energy expenditure was between-subject variation related to gain in fat mass? Not basal metabolic rate and not the thermogenesis of eating. There was a powerful negative correlation between NEAT and fat gain. The more fidgety the person, the lower the weight gain. Levine has gone on to design a unique office, which facilitates NEAT. The telephone is as far from the desk as possible. The desk can be elevated to facilitate standing and he has also designed an award-winning desk[1], which has a two-mile an hour treadmill option to facilitate NEAT (http://store.steelcase.com/products/walkstation/).

We have as much obligation to tackle our obesogenic built environment, as we have to tackle our food intake. However, architects and ergonomic designers of comfortable offices are not as attractive a villain as is the corporate food sector.

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[1] Invention of the Future Award from NASA, and the Innovation Award at the World Fair

Eating up the food miles

I recently heard a radio interview with Dr I. Eatwell (I can’t remember her real name but she was a Californian food-head) who told us about her weekly cycle jaunt out of the small town of Davis in California to pick wild herbs.  We were, of course, all supposed to gasp in admiration at her zeal to seek and eat local. In a sense, she was emulating the famous French aristocrat who suggested that, in view of the shortage of bread: "Qu'ils mangent de la brioche" or “Let them eat cake”. Quite simply, there are not sufficient wild herbs to meet the gastronomic needs of the firm and courageous citizens of even a small town such as Davis. Moreover, since Dr I. Eatwell harvested the herbs before the seeding period, she selfishly pulled the plug on food chain sustainability. The concept of local food is elitist and unworkable for the general population. So let’s do the sums. According to Sustainable Table, we should confine our food choice to 100 km radius. Lets extend that to 120 km to allow for the area of a large city. That translates into about 4524 hectares which if farmed for wheat would yield 38,798,324 kg of wheat, translating into 27,158,826 kg of flour or 108,635,307,000 calories. Assuming a daily energy need of just 2,000 calories, we would have enough to feed about 150 persons a year.  So the theory works for towns with a population up to 150,000 and of course the nearest other town must be 240 km away, otherwise there would be territorial battles where their circles overlap. It just doesn’t work for today’s demography. Of course a few privileged elite can easily achieve this but its cake for the rest of us.

One of the smart things mad did which no other species achieved was the division of labour: “I’ll buy the peas you grow on your farm and you can buy tractor insurance from me”.  The chore of being responsible for the provision of our own food was passed on to farmers who in turn passed on responsibility for education, power and so forth. Many centuries ago, those farmers were local but as modern transport evolved, we bought food that was grown far away, often continents away. And so the high priests of healthy eating introduced the concept of “food miles” and “eating in season”. I will surely eat a strawberry this Christmas or find one on my champagne glass and I’m not in the least bit bothered that it might come from Spain or Greece. And I might concede that if I were to pluck a fresh strawberry in season in County Wexford it would taste better than the imported and out-of-season variety. But that imported and out-of-season variety still is unmistakably strawberry in every olfactory sense if you’ll excuse the pun (did I just punnet!). Not only does it taste and smell of strawberry, but it has the exact nutritional composition that the in-season County Wexford strawberry has and I can vary my diet to include imported and out-of-season fish, fruit, vegetables, yams and so on. The overall health of the nation would improve if we were to eat more fruit and more vegetables. Any implication that these foods have to be sourced locally and in-season is utterly unhelpful.

Food miles are another obsession with the high priests of health eating. The implication of counting food miles is that local is best and the greater the food mile the greater the sin. As ever, when put under the microscope, things are not so straightforward. An apple, grown locally and sold at the end of the season just before a new harvest, carries little mileage but it has consumed a significant quantity of energy keeping it nice and juicy through autumn and into spring. Without that energy consuming technological intervention, the apples would rot.   In contrast, a New Zealand apple, just harvested in that beautiful country and consumed in Dublin carries huge mileage but has used relatively little energy. Locally grown low mileage tomatoes require a glasshouse and yet more energy while imported ones are grown where the sun shines all day, yielding high mileage and low energy.  And of course, one of the biggest contributors to the energy cost of food occurs when it leaves the supermarket shelf. Driving there and back, freezing, chilling and cooking food all gobbles up energy. And of course, there is food waste. Sin scéal eile, which, for the Sassenachs among you, translates into: “That’s another story”

Dying for Christmas

According to the experts and politicos in public health nutrition, the greatest food-related condition on the planet is obesity.  That is not so. The fat and overweight all over the world will enjoy hearty feasts this Christmas or at their equivalent major holiday. It is hunger that is the greatest food-related condition facing mankind. One billion of the globe’s citizens will go to bed hungry on Christmas night, as they do every night. That is one in 6 of our fellow humans.  They live mostly in South Asia and in sub-Saharan Africa. By 2050, over 95% of the growth in the global population to 9 billion will be in these two regions. So too will be the worst effects of climate change in reducing agricultural output. Aside from the de-humanizing effect of hunger, there follows in its food steps a whole slew of diseases, mostly infectious diseases, caused by a greatly impaired immune system.  The consequent daily death rate from hunger is equivalent to 30 fully laden jumbo jets crashing each and every day with all lives on board lost. Never forget that statistic.

The hungry are not forgotten of course. They are constantly in our thoughts and most importantly in the thoughts of our political leaders and our major global agencies. They have been in their thoughts for the last 50 years as the following quotes show:

We have the ability, we have the means, and we have the capacity to eliminate hunger from the face of the earth. We need only the will.

President John F. Kennedy, 1963

Within one decade no child will go to bed hungry, no family will fear for its next day’s bread, and no human being’s future and capacities will be stunted by malnutrition. Every man, woman and child has the inalienable right to be free from malnutrition and hunger

World Food Conference, Rome, 1974

As a basis for the Plan of Action for Nutrition . . . we pledge to make all efforts to eliminate before the end of this decade: famine and famine-related deaths; starvation and nutritional deficiency diseases in communities affected by natural and man-made disasters; iodine and vitamin A deficiencies.

World Declaration and Plan of Action for Nutrition, Rome, December 1992

The Rome Declaration calls upon us to reduce by half the number of chronically undernourished people on the Earth by the year 2015 . . . If each of us gives his or her best I believe that we can meet and even exceed the target we have set for ourselves.

World Food Summit 1996

Goal 1: Eradicate extreme poverty and hunger; Target 2. Halve, between 1990 and 2015, the proportion of people who suffer from hunger.

 UN Millennium Development Goals 2002

We have seen in the present crisis among the states of the euro zone a generally selfish attitude of individual member states. On a global basis, a similarly selfish attitude has impeded progress with regard to climate change. In each case, the individual member states have a strategic interest, which is influenced by its business community and by many non-governmental organisations.  What hope has hunger got? The various quotations above show that we are kidding ourselves and paying lip service to the problem. In his book ‘Common wealth: Economics of a crowded planet’ the distinguished leader in development studies Jeffrey Sachs points out the need for a global solution to the problem. But how can we persuade the business and NGO communities in Ireland and elsewhere that global hunger is an issue of major importance and of sufficient importance to merit significantly more investment than we give at present? “We are in a recession” might be the general response. For the hungry, there is no recession since you can only recess from what has been progressed and, in their case, there has been no progression. Africa can help itself but not without our help. So, right now, take out the credit card and in multiples of 6 make a donation now to your favourite aid agency. If you don’t know of one immediately, try my favourite: https://www.concern.net/donate.

The inherent flaws of food intake data

The inherent flaws of food intake data

Measuring our dietary patterns and linking it to patterns of disease is at the core of modern nutritional epidemiology and such data drive national and global food and nutrition policy. There is, however, a serious and inherent flaw in the measurement of food intake which modern nutritional epidemiology tends to forget. That flaw is energy under-reporting. Our energy requirements are composed of several factors, the most important of which is resting metabolism which accounts for about 85% of energy needs in a normal adult following a typical sedentary western lifestyle. These energy needs are to keep our hearts beating, our lungs breathing, our kidneys filtering, our brains remembering and so on. We can directly measure this as a person’s resting metabolic rate (RMR) using a calorimeter and there are also a number of ways of doing so indirectly, some of which are  extremely accurate. We can also calculate our RMR using a number of equations and you’ll find plenty of calculators on the internet. My RMR is 2,030 calories. Because I’m sedentary, except for golf on a Saturday morning, I need to up that figure by about 15% to 2,335 calories to take account of my daily ohysical activity. A very sporty person would have a higher multiplier of RMR.  If I was a volunteer in a dietary survey and I reported an energy intake of 1,900 calories, then ocviously I must be dieting. If I say I’m not dieting and that this is a typical dietary intake, then I’m under-reporting. There never has been and there probably never will be a large survey, large enough to be of value to epidemiology, which does not have some element of under-reporting. And the level of under-reporting is huge - anywhere from 30% to 50%. We know this to be so using both simple equations to measure RMR and also using very sophisticated stable isotopes.

Why do people under-report? We know it is higher among females amd we know it increases with increasing body weight. My explanation, which is not based on any experimental data but on supposition is as follows. Most people with a western sedentary lifestyle, have at some time sought to lose weight. They inevitably start on Monday morning. Come Thursday, something happens, good or bad and the dieting pattern is gone. Its back to normal to start all over again next Monday morning. This cyclical pattern is familiar to many people. So, when asked to take part in a dietary survey and when pressed to be truthful in every way to report their habitual intake, which days do they deem to be “typical?. I’m afraid that 30-50% of people deem the dietary restrictive days of Monday, Tuesday and Wednesday to be normal. Thus they don’t deliberately lie but they do under-report their food intake. In effect, food intake data are flawed and we have to live with that for now until we come up with some smart way of overcoming this problem.

Because under-reporting is higher among the over-weight and obese, many assume that the foods that are under-reported tend to be the so called “guilty” ones: foods high in sugar and fats such as fast food, soft drinks, savoury snacks and so on. This assumption is of course false since obesity is associated with ALL foods (see blog of November 6th: “Taxing the fat and sweet”). Not surprisingly, when we examine food intake data in those with plausible energy intakes against those under-reporting food intake, we find all food categories under-reported.

This issue of energy under-reporting is dismissed by nutritional epidemiology on the grounds that all their propsed statistical associations of diet and disease are adjusted for all of those factors of importance in under-reporting (body weight, energy intake, gender, age etc). However, there is an increasing number of researchers who are showing that this statistical adjustment is flawed when it comes to under-reporting food intake. Basciaclly, an average daily intake of a food is composed of three elements. Firstly, the population average embraces  both consumers and non-consumers of the food in question. Some people who under-report energy intake may simply deny eating one or more foods. That is the first route of under-reporting. The second is that they admit reporting but under-report the frequency of consumption. The third is that they admit eating the food, are truthful about the frequency of intake but are untruthful with the portion size they report. Of course any combination of these is possible. There is simply no way in which statistical jiggery-pokery can unravel this web of deceit. So we have only one option. We create a cut off point (RMR + 15% of RMR) for energy requirement and anyone falling below this is excluded from the analysis. Its painful to lose subjects in this way when statistical power is dependet on adequate numbers.

Without doubt the area of greatest concern over the distorting impact of energy under-reporting is in relation to obesity. Firstly, the scale of under-reporting rises considerably with rising body weight. Secondly, obesity is such a hot topic as regards candidate foods for taxation or labeling. How can we be so confident in shaping public health nutrition policy in obesity when (a) we know that food under-reporting is generally a problem but particularly a problem in obesity and (b) when there is no hope of any statistical trick separating out the three lines of mis-reporting: denying ever eating the food in question, not accurately reporting frequency of the intake of a target food and finally, under-reporting portion size. It bothers me a lot but its a mere nuisance to the high priests of public health nutrition who know both  the problem and the solution. 

The epidemic of obesity ~ as fat as it gets

The epidemic of obesity ~ as fat as it gets

John Minnoch (1941-1983) lived in Seattle and is credited in the Guinness Book of Records as being the heaviest male in history. At 6 feet 1 inch tall, he weighed 442kg, equivalent to a BMI of 128. That equates to the biomass of just 4.5 Irish adult males! Now when we talk about the epidemic of obesity, there is a possibility that some people might think that a significant fraction of the population would reach the weight of John Minnoch. That is not how it works. Several years ago Steve O’Rahilly, Professor of Medicine at Addenbrooke’s Hospital Cambridge and a world authority on the genetics of obesity, raised the possibility that the epidemic of obesity was beginning to level off in the UK. Thus, faced with an obesogenic environment, the population variation in genetic predisposition to obesity is such that those who can cope with this environment will remain within the normal weight range while those susceptible to an obesogenic environment will attain a level of over weight or obesity up to their genetic potential. Two recent papers now put flesh on O’Rahilly’s speculation.

The first of these papers gathered data on time trends in obesity over the period 1999 to 2010.  The authors of the paper[1], from the Institute of Preventative Medicine at Copenhagen, set out a total of 7 criteria, which had to be met if a published study was to be included in their analysis. For example, the sample size had to be greater than 5,000 and data on weight and height had to be measured directly and not self reported. Thus out of 52 studies, only 44 met the 7 inclusion criteria. They also graded the studies into very high, high, medium or low quality. Of the 6 studies graded very high quality data, 5 showed that obesity rates were stable during the period 1999 to 2010. These 5 were from France, Sweden, England, Greece and Australia and only in China did a very high quality study show an in crease in obesity. Among children and adolescents, there was a clear trend toward a stabilization of obesity across continents and while the pattern among adults was less clear-cut, nonetheless, stabilization was generally evident.

The second study comes from Australia, actually from a rather distinguished WHO Collaborating Centre for Obesity Prevention, and it looked at obesity trends in preschool children over the period 1999 to 2007[2]. They studied two cohorts, one aged 2 years old in 1999 (130,000) and the other 3.5 years old in 1999 (96,000), each of which was followed annually to the year 2007. Weight, height (and length for younger age groups) were measured annually. Whereas in 1999, some 2.5 % of 2 year olds were obese, in 2007, this fell to 1.7%. For three year olds in 1999, the comparable figures were 4.5% and 2.9%. Similar trends were seen when obese children were combined with over weight children (from 13.5% to 12.4% in the 2 year old cohort and from 18.5% to 15.4% in the 3.5 year old group over the period 1999-2007). Although the overall rate of obesity and overweight was higher in the lower socioeconomic groups, the rate of decline in fatness was highest in these groups.

The first study would suggest that, as expected, the variation in the genetic potential to develop obesity would ultimately be met and that the prevalence rate would stabilize. It doesn’t mean the problem has gone away since obesity will continue to be a major drain on the economics of our health care systems. What it will do is to increase the focus on the management of the physiological disadvantages of obesity and overweight and in that regard, a greater emphasis on the promotion of physical must emerge, since nothing compares with physical activity as an antidote to the adverse effects of obesity. In the case of the Australian study of preschool children, the data suggests that there is a greater awareness of the problem of obesity among parents, particularly those who are socially disadvantaged. Preschool children do not make their own food choices so this reflects a mind change of mums and dads. Whether this all translates into fewer obese adolescents remains to be seen.

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[1] Rokholm R et al Obesity Reviews (2010) 11, 835

[2] Nichols MS (2011) International Journal of Obesity 35, 916-024

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 6^th 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.