Obesity and Nature v Nurture re-visited

In the obesogenic environment that we live in, not everyone becomes obese. To the high priests of nutrition, that variability is put down to variation in self-control and self-discipline and that in turn relates to level of education and social class. The idea that this variation might be genetically based is dismissed with the old reliable falsism that since our genes have not changed during the recent epidemic of obesity, it’s the environment that counts. Well, yet another twin study shows that this is nonsense and this twin study is somewhat special since it pooled data from 23 twin cohorts from four countries: Denmark, Australia, Canada and Sweden involving just over 24,000 children[1]. Moreover, this pooling study was able to provide data on twins from birth through 19 years of age. By comparing variation within and between both identical and non-identical twins, it is possible to distinguish the effect of genes from the effect of the environment and the latter can be split into common and unique environments. At birth, only 8% of variation in weight or body mass index (BMI) could be explained by genetic factors. By 5 months this had increased to 65% and rose into the 70% decile up to 9 years of age. In the early teens the genetic variation had reached into to 80% decile and by late teens it had hit 90%.  As children got older, the environmental explanation of obesity had fallen from 74% at birth, to 25% at 6 years and down to about 10% in late teens. While this study clearly shows the powerful effect of genetic factors on obesity, it does raise the question as to why this genetic dimension increased with age. Clearly, the genetic make up remained constant so most likely, changes in gene expression were the contributory factor. Growth in childhood and especially in adolescence is associated with significant biological adjustments, which could create the environment for altered gene expression.

One of the reasons which I personally think public health nutritionists are wary of the genetic influence on obesity is that the subject is strongly orientated toward basic biology, effectively, the digestion, absorption, transport, distribution and utilisation of calories from fat, carbohydrate, protein and alcohol. However, genetic influences on behaviour are to my mind far more important   than the genetics of basic biological elements. A recent twin study has looked at the heritability of taste[2].  Subjects were given a strawberry jelly with or without the hot spice capsaicin derived from chili peppers. They were also asked questions on their liking or otherwise of spicy foods and spices and of foods that have mild, strong and extremely strong pungency properties. 50% of the variation in preference for spicy foods and spices and 58% of the variation in “pleasantness of strong pungency” was explained by genetic factors. Another twin study looked at food neophobia in a group of children aged 8 to 11 years, comprising 5,390 pairs of identical and non-identical twins[3].  Parents were asked about their children’s attitude to foods with four statements: “My child is constantly sampling new and different foods”, “My child doesn’t trust new foods,” “My child is afraid to eat things/he has never had before.” and “If my child doesn’t know what’s in a food s/he won’t try it.” A food neophobia score was worked out and the highly robust finding of the study was that a staggering 78% of variation in food neophobia was genetic in origin. Only 22% was learned from the environment. These studies show that the genetic component of obesity need not be related to the biochemistry of energy metabolism, but rather to more complex behavioural traits such as food choice.

Twin studies of obesity always raise the question of assortative mating, that is fat partners mating with other fat partners and similarly for slim partners. Assortative mating has been shown to occur in personality type, education, religion, politics, age, smoking habits and anti-social behaviour. Researchers at the Rowett Institute in Aberdeen used DEXA scans to accurately measure body fat levels in 42 couples[4]. Strong evidence for assortative mating in relation to body fat was found. For example, subjects with disproportionately large arms assortatively mated with like partners. Given the high heritability of the propensity to develop obesity, assortative mating will accelerate the incidence of obesity sine the children of such parents are likely to inherit genetic patterns from both parents.  

The high priests of public health nutrition may dislike the implications of a genetic dimension to obesity but they are being increasingly isolated from the scientific truth.

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[1] Dubois et al (2012) PLoS ONE 7, e30153

[2] Tornwall et al (2012) Physiology & Behaviour, 107, 381-389

[3] Cooke et al (2007) Am J Clin Nutr 86, 428-433

[4] Speakman et al(2007) Am J Clin Nutr 86, 316-323

Sugar taxes and weight loss predictions

The Danish government has abandoned its tax on fat and and its plans for a sugar tax.  A spokesperson for the tax ministry is quoted thus: “The suggestions to tax foods for public health reasons are misguided at best and may be counter-productive at worst.  Not only do such taxes not work, especially when they choose the wrong food to tax, they can become expensive liabilities for the businesses forced to become tax collectors on the governments behalf”[1]. Shortly we will have our annual budget here in Ireland and notwithstanding the volte-face of our Danish colleagues, the likelihood is that we will face such a tax soon.  In general, the predicted weight changes associated with projected taxes on sugar sweetened beverages are grossly overestimated.

A recent consensus statement of the American Society of Nutrition (ASN) and the International Life Sciences Institute (ILSI) has examined the topic:  “Energy balance and its components:  Implications for body weight regulation”[2].  One of the areas covered by this paper is the popular and widely held belief that to lose 1lb of body weight, you need to reduce caloric intake by 3,500 kcal.   This figure assumes that a loss of 1lb of body weight is made up entirely of adipose tissue which is 86% fat and the fat has 9 kcal per gram.  This 3,500 kcal figure is widely used in predicting the benefit of weight loss from a sugar sweetened beverage tax.  It has many flaws.

Firstly, a 1lb weight loss will not be 100% fat but will also involve the loss of some lean tissue (muscle and protein elements of adipose tissue and its metabolism).  Whereas fat has an energy value of 9 kcal/g, lean tissue has a value of 4 kcal/g.  The exact ratio of the loss of lean and fat in weight reduction depends largely on the level of fat in the body at the outset.  The higher the intake level of fat, the higher the proportion of fat lost.  However, as a person sheds fat, the ratio of fat to lean changes in favour of the latter, so subsequent weight loss will have a lower ratio of fat to lean.  The blanket use of the 3,500kcal value ignores this.

The second criticism of this rule is that it ignores time.  If you shed 3,500kcal per week every week, that would differ from a deficit of 3,500 kcal per month every month.  The former leads to a daily deficit of 500 kcal while the latter is just 117 kcal.  Even the most non-expert dieter knows that such differences in daily energy deficits will lead to radically different rates of weight loss.  Thirdly, the 3,500 kcal rule assumes complete linearity – in other words the rule equally applies, pound after pound of weight loss. We saw above that progressive weight loss will progressively increase the % of that weight loss as lean tissue but more importantly, the 3,500kcal rule ignores a major adaptation in energy expenditure.  Basically, our basal metabolic rate (BMR) falls as we restrict our caloric intake.  Since BMR accounts for 88% of energy expenditure in most sedentary persons, that means that a fall in BMR represents a significant adaptive response through increased efficiency of energy use making weight loss progressively more difficult.

Researchers at the US National Institute of Health have developed a very detailed mathematical model which predicts weight loss based on a wide variety of inputs[3].  The model has been validated against a number of highly controlled weight loss programmes.  Together with researchers based at the USDA and the economics departments of the universities of Florida and Minnesota, they have examined the likely weight loss that would accrue from a tax of 20% (about 0.5 cents per ounce) on sugar sweetened beverages in the US[4].  They concluded that the nutritional input would be a reduction of energy intake of 34-47 kcal per day for adults.  Using the 3,500 kcal rule, an average weight loss of 1.60kg would be predicted for year 1 rising to 8kg in year 5 and to 16kg in year 10.   However, when the dynamic mathematical model is used, the corresponding figures for years 1, 5 and 10 are, respectively, 0.97, 1.78 and 1.84 kg loss.  The % of US citizens that are over-weight is predicted to fall from existing levels of 66.9% over-weight to 51.5% over-weight in 5 years time using the 3,500 kcal rate but using the dynamic mathematical model, the 5-year figure for the over-weight population in the US would be just 62.3%.  Clearly, the continued use of the 3,500 kcal rule in predicting weight loss should cease and the recommendations of the consensus statement of the ASN and ILSI should apply: “Every permanent 10 kcal change in energy intake per day will lead to an eventual weight change of 1lb when the body reaches a new steady state.  It will take nearly a year to achieve 50% and about 3 years to achieve 95%”.

My back of envelope calculations based on the National Adult Nutrition Survey is that extrapolating from the US model (footnote 4), a tax on sugar sweetened beverages might lead to a weight loss of 0.6 lb at the end of year 1. That of course is subject to an error estimate such that it might be higher but equally, it might be lower. Many of the advocates of fat taxes might argue that they will take that “thank you very much” as a start and then move to the next food. But you cannot continue to add tax to the cost of food.

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[1] http://www.foodnavigator.com/Legislation/Danish-government-scraps-fat-tax-cancels-planned-sugar-tax

[2] Hall et al (2012) Am J Clin Nutr 12, 989-994

[3] Hall et al (2011) Lancet 378,826-837

[4] Biing-Hwan et al (2011) Econ Hum Biol 9, 329-341

Dolly Parton and the art of dieting

Sometime back in the early 1990s or thereabouts, Dolly Parton was being interviewed by the famous BBC chat show host, Michael Parkinson. When asked about what diet she used to keep her figure, she replied: “Honey, if you want to lose weight, get your head out of the slop bucket”.  In other word, just eat less. No truer words were ever uttered in the vast realm of advice on dieting. This year we have seen a number of scientific papers published on sugar sweetened beverages, some designed to boost weight gain and some designed to induce weight loss, all adding to the belief that sugar sweetened beverages are both the cause and the cure for modern obesity. A recent paper from the Department of Nutrition at Harvard will help put things in perspective, but only for those wishing to have an accurate perspective.

The first [1] of the sugar papers looked at four groups each given 1-liter of a beverage per day for 6 months. Group 1 receiver a liter of regular sugar sweetened Coke. Group 2 were given a liter of semi-skimmed milk with an approximate equal calorie level to the Coke. Groups 3 and 4 respectively received 1 liter of diet Coke or water. According to the authors, the consumption of the energy-containing beverages led to a compensation effect with a reduction in the intake of other foods and no overall change in energy intake. No dietary data are provided in the paper but 1 liter of regular Coke would have diluted out its equivalent caloric value from all other foods, leading to a reduction in the intake of the latter by 430 calories per day. This Coke group showed a significant accumulation of fat in the liver compared to others but we will never know if it was due to the absurdly high total intake of sugars (about double the normal according to my calculations) or to a reduction in the intakes of micro-nutrients associated with 430 less food than normal every day. Coke for example, does not contain, the B-vitamin riboflavin, but low riboflavin status will lead to increased blood pressure, and the authors did see a rise in blood pressure with regular Coke. 

So, 1 liter of Coke per day did not lead to weight gain ( for example a 1.3% gain with Coke and a 0.8% gain with water). However, two studies reported in the New England Journal of Medicine show that if sugar sweetened beverages in children are replaced with a calorie free version, then weight loss does occur [2]. These studies will be widely cited as evidence that sugary drinks cause obesity. In fact, these studies simply show that if you do as Dolly Parton says, and simply eat less, you will lose weight so the weight loss could have been with any caloric source, not just sugar-sweetened beverages.

Which brings me to the Harvard paper [3]. This study (a subset of a larger dietary intervention) looked at how variation in the distribution of calories in a weight loss regimen influenced weight change and also changes in body composition. Four dietary treatments were used and an energy deficit of 750 kcal per day was the target for each participant. The diets varied the level of fat, protein and carbohydrate. At 6 months, the average amount of fat lost was 4.2 kg and the loss of lean tissue was 2.1 kg.  About half of this fat loss was due to loss of fat from the abdominal fat with about a third lost from subcutaneous fat. Only 0.1 kg of fat was lost from the liver but this represented a loss of 16% of liver fat. There were no differences in any of these measures according to the composition of the weight reduction diets, again, upholding the Dolly Parton rule.

In summary, the first study tells us that if you oblige subjects to eat a 1-liter bottle of regular Coke every day, you won’t gain weight because you reduce your intake of other foods keeping energy intake constant. The second tells us that extracting calories from children’s diets will lead to a weight loss, in this case using sugar sweetened beverages as the target food. The third tells us that Dolly Parton was correct. It really doesn’t matter what the composition of your weight reducing diet is so long as the caloric restriction operates.

So for what its worth, here are my basic rules about successful dieting:

1.      Never start a diet until you have though about it long and hard given that the relapse rate of weight loss is so high.

2.      Never start a diet until you have built physical activity into your daily routine. Physical activity will reverse the negative effects of obesity such as poor glucose management, higher blood pressure and elevated blood lipids.

3.      Don’t diet on your own. Join a weight loss group and get the benefit of the social network of dieting and maintaining weight loss. 

4.      Heed Dolly Parton and just eat less and eat according to your preferences

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[1] Maersk M et al (2012) Amer J Clin Nutr 95 (2) 283

[2] de Ruyter et al (2012) New Engl J Ned 367 (15) 1397

[3] de Souza RJ et al (2012) Amer J Clin Nutr 95 614

A bad day at the lab for GM reserach

During this summer, I recall reading in the Sunday Times that the environmental NGOs are beginning to re-think their strategy on GM foods. I see some evidence that this is the case since I cannot find any mention of the following paper on any of their websites: Séralini et al (2012) “Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize”[1]. The publication of this paper has led to the greatest backlash by the scientific community that I have seen in 4 decades in this business. Essentially, Séralini published a paper showing that rats exposed to a GM food (maize) and a herbicide (which is used with the resistant GM crop) developed breast tumors significantly faster and to a greater extent than controls rats over 104 weeks (2 years). The most significant critic is the European Food Safety Authority (EFSA), which is the independent body charged with protecting consumer health in the EU and which is the judge, on the consumers’ behalf, of all scientific publications on food safety including those on GM technology.

The authors used Sprague-Dawley rats that will naturally develop tumors over their lifetime irrespective of any dietary or other treatment and the authors did not discuss the implications of this natural tendency to tumor development for their study. They also used 10 rats per treatment, which according to OECD protocols is adequate for standard 90-day toxicity studies. Monsanto’s submission to EFSA on the GM maize (NK603) used only 10 rats per treatment, but it was for a 90-day toxicity study. However, Séralini’s study was over a “lifetime” and the OECD guidelines recommend the numbers now be increased to 20 per treatment for chemical toxicity tests but that for carcinogenicity studies, this should be increased to 50 per treatment. In an article on this topic, Nature contacted Harlan Laboratories who supplied the rats and were told that for this strain of rat, only 33% of males and 50% of females live to 2 years. According to the OECD protocols, if a study is to last 104 weeks, then the survival rate should be 50% at least and that then 130 rats (half male half female) should be used per treatment.

The lead author apparently agrees that more rats per treatment would have boosted his statistical power but according to Nature[2], he argues that he did not design the study to find tumors.  If at this stage you are confused, then you’re normal!!!

Further criticism from EFSA includes the fact that no information is given on the composition of the rat diets and that no data is given on how much of the herbicide was consumed through its route, drinking water. No data are given on lesions that were found which were not tumors or dropout rates and reasons for dropouts. In addition, the EFSA working group state that the statistical techniques used were not “commonly-used statistical methods” and that the authors do not state whether the unusual statistical techniques they used were, in fact, the a priori choice and if so, why so? Finally EFSA requested the basic data from the authors to examine these shortcomings and they were refused access. Trust is hard won but easily lost. 

If all that wasn’t bad enough, Nature reports on a very sinister dimension to this saga, which has not received widespread attention. According to their correspondent, Declan Butler, the author orchestrated a very tight media offensive that included a film and his new book (Tous Cobayes: OGM, Pesticides, Produits Chimique: All Guinea Pigs, GMOs, pesticides and chemicals) on the work. A select group of journalists were invited (not from Nature) to preview the paper and were asked to sign a confidentiality agreement demanding total secrecy until formal publication. A breach of the terms of the confidentiality agreement would require, according to Nature, the following: “A refund of the cost of the study of several million euros would be considered damages if the premature disclosure questioned the release of the study”. I’m in the wrong business I believe!!!!

The Ethics Committee of one of France’s most august academic bodies Centre National de la Recherche Scientifique described the PR exercise as “inappropriate”.

Who’d like to be the first to write a review of his new book on Amazon[3]? Well although I would, it would be so slanderous that I could not ever afford the libel fee I’d have to pay.

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[1] Séralini GE, Clair E, Mesnage R, Gress S, Defarge N, Malatesta M, Hennequin D, de Vendômois JS. Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food Chem Toxicol. 2012 Nov;50(11):4221-31

[2] http://www.nature.com.eproxy.ucd.ie/news/hyped-gm-maize-study-faces-growing-scrutiny-1.11566

[3] http://www.amazon.co.uk/Tous-cobayes-pesticides-produits-chimiques/dp/2081262363/ref=sr_1_1?s=books&ie=UTF8&qid=1350944840&sr=1-1

Fat Englanders ~ 200 years ago

(Apologies for non-publication of some recent blogs but China still poses Internet challenges)

William Wadd, born in London in 1776. He was from a medical family and he followed in that tradition, becoming a Member of the Royal College of Surgeons of England in 1801. After a distinguished career in medicine, he was appointed one of the Surgeons Extraordinary to King George IV in 1820. Wadd wrote notes on his favourite topic, obesity and although he always proposed to tidy them up for into a book, they were in fact published in unedited form in1816. His book (still available on Amazon) bore the lengthy title: ”Cursory Remarks on Corpulence, Or, Obesity Considered As A Disease: With a Critical Examination Of Ancient And Modern Opinions, Relative To Its Causes and Cure.”  What is singularly important about this book is its comments on obesity and its prevalence, its perceived causes and consequences and on its social context all at the turn of the 18^th century. For those of us interested in obesity all of 2 plus centuries later it is worthwhile reflecting on some of the comments of Dr Wadd.

Epidemiology: Of the general epidemiology of obesity prevailing at the time he writes: ”If the increase of wealth and the refinement of modern times, have tended to banish plague and pestilence from our cities, they have probably introduced the whole train of nervous disorders, and increased frequency of corpulence”.  He goes on to argue that: ”It has been conjectures by some that for one fat person in France or Spain, there are an hundred in England.” These comments on the widespread prevalence of obesity 300 years ago is in direct conflict with a key assumption of Robert Kessler in his popular bestseller “An end of overeating” is that obesity is more or less a recent phenomenon…. A measure of opulence that surprises one at first but on reflection should not surprise us at all is the advent of chimneys. Wadd cheekily ponders the adornment of houses with chimneys but speculates that there is no associated record “…of the front of a house or the windows being taken away to let out, to an untimely grave, some unfortunate victim, too ponderous to be brought down the staircase”!

Genetics: “The predisposition to corpulency varies in different persons. In some it exists to such an extent, that a considerable secretion of fat will take place not withstanding strict attention to the habits of life and undeviating moderation in the gratification of appetite. Such a predisposition is often hereditary”. It is interesting to note that 300 years ago there was recognition that obesity had a genetic dimension, which modern research shows to be of the order of 75% in terms of heredity but which is still so hard to stomach for the high priests of health eating.

Social class and the obesogenic lifestyle: “Yet even such dispositions [hereditary] seem to require certain exciting causes to bring them to action. Of these, a free indulgence of the table is principal. For it must be admitted that the lower orders of society, the poor and the laborious are seldom thus encumbered and it is only among those who have the means of obtaining the comforts of life, without labour, that excessive corpulency is met with. You may see an army of forty thousand foot soldiers without a fat man. And I affirm, that by plenty, and rest, twenty of the forty shall grow fat.”

Comments on causes: ”The article of drink requires the utmost of attention. Corpulent persons generally indulge to excess; if this be allowed every endeavour to reduce them will be in vain”. Boo-hoo for the boozers! On sugar he wrote: ”Negroes in the West Indies get fat at the sugar season” and he also commented: “The following case, which occurred in my knowledge, seems to prove how readily the saccharine particles of vegetables contribute greatly to increase bulk”. He then goes to describe a case history of a brewer who got fat, not on the alcohol but on the “sweet wort” from which it was brewed.

Treatments: He describes very many treatments from vegetarianism (the most popular), the consumption of vinegar or soap, salivation, perspiration, exercise or bandaging. He concludes: ”These are the principal articles that have been resorted to in the treatment of this disease; and the person who depends solely on the benefit to be derived from the use of any of them, will find himself grievously disappointed”.

“How can a magic box of pills,

Syrup, or vegetable juice,

Eradicate at once those ills,

Which years of luxury produce”

200 hundred plus years and nothing much has changed!!

Calorie restriction for longevity ~ For mice, not man

Work in any field long enough and you get a “nose” for the job. It is an instinctive reaction to some new event or idea, built on decades of the passive accumulation of knowledge in ones chosen field. I’ve acquired such a nose an did so quite early on. Instinctively, I could spot a good, original and potentially new area of interest among a forest of dross. Equally, I could sniff a no-hoper, a line of research rapidly going nowhere. I first heard a lecture on calorie restriction over 15 years ago, appropriately at a hotel affiliated to the Orlando Disney Park. Rats, whose energy intake was restricted to 15 - 25% of caloric intake, lived longer than rats given as much as they liked to eat of standard rat chow. I neither like nor dislike rats but it remains that I really have no feelings for them of any substance. The fact that the caloric restriction made them live longer was really of no interest to me, other than to wonder how rats feel about longevity in a captive and restricted, if not slave-like existence. However, translating this to humans really made me titter. We live in an extraordinarily obesogenic environment with overweight and obesity abounding and growing in prevalence to every corner of the globe and with quack diets and trash books for every desirable attribute, including weight loss and aging, dominating the mass media. So, it appears from the rat handlers, that  we are to think about adding caloric restriction as an additional string to our public health nutrition bow to beat the grim reaper and steal a few more mortal years. As one of my teachers used to say in exasperation in class at daft responses: “Ye gods and little fishes.”

The effect of caloric restriction on longevity was first reported in 1935 and has now been studied in yeast, worms, flies and rodents and a 15-15% restriction in energy intake in the latter can increase longevity by up to 60%. Such is the wealth of data on these  diverse species that one must accept the literature that caloric restriction prolongs life expectancy. The big question is the translation of that concept to man. Relative to these species, we mature far more slowly and have a longer life span. People often talk about human equivalents of “dog years” but in absolute terms, we outlive dogs by at least 8 fold.

The Calorie Restriction Society^[1] boasts 7,000 members. One such member is described in a journalistic piece on the web site. This member is 48 years old, is fit as a fiddle, weighs 118 pounds which is 7 pounds less than the minimum recommended for his height, he confines his energy intake to 1,500 calories a day and although his energy expenditure is not described, he would appear to be very physically active. He first got interested in caloric restriction as a tool to longevity when he was faced with his first manifestation of aging, a receding hairline. Poor guy!!!

The whole are of calorie restriction took a hit recently when the National Institute on Aging published its long term study of energy restriction on longevity in rhesus monkeys, a species far closer to man than yeast, flies, worms and mice^[2].   A 20 year study examined the effects of caloric restriction introduced to rhesus monkeys at varying stages of life. No statistically significant differences were observed between control monkeys fed ad libitum and those calorie-restricted (10-40% restriction). The latter did achieve a longer life span than would normally be expected for this species but the authors point out that they lived a privileged life of good husbandry and veterinary care. The main causes of death did not differ between the two groups:cancer, cardiovascular disease and general organ deterioration. However, generally recognised beneficial biomarkers of health increased in the caloric restricted monkeys but this did not translate into a longer life. In fairness to the literature, another colony of monkeys elsewhere (different diet, management and breeds)  did respond but in the world of science, it only takes one black swan to demolish a theory. The recent Nature paper is that black swan.

From a practical point of view, I can see a few dedicated enthusiasts sharing the necessary skills via social networks to achieve successful caloric restriction but I fail to see how it would be dealt with the great majority of the people. Leaving aside the ever-present obesogenic food supply, how is the average person to know exactly what their energy requirements are and then how to pare that down by 20% or more of that to achieve the required level of calorie restriction? How, especially with increasing age, do we ensure that caloric restriction does not drift into malnutrition which in the older population is so strongly associated with increased admission to hospitals, increased complications hen there, longer stays and more frequent re-admissions. Professor James Hill of the University of Colorado in his excellent book “The Step Diet” ^[3], recommends 25,000 steps per day plus rejection of 25% of the food served at every meal, just to maintain weight loss. For the many fatties among us, moi included, there is (a) the need to shed pounds to an appropriate avoirdupois a la James Hill and (b) having done so, to then hit a 25% calories restriction.

It ain’t going to happen. My nose was right!

Finally, apologies for the late post of this blog but that happens. Also next two mondays are in Asia and a lot of teaching at China Agricultural University in Beijing and Honk Kong University so I’ ll try but please be understanding!

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^[1] http://www.crsociety.org/

^[2] Mattison JA et al (2012) Nature, 489 (7415), 318-321

^[3] http://tinyurl.com/9pbpbh3

Genes, memes and obesity

I have blogged several times about the uniqueness of obesity to the human race. Notwithstanding the fact that we share 98% of our genes with our nearest biological relatives, the chimpanzees, we alone get fat. It therefore follows that our obesity has origins in the basic biology of energy metabolism and storage but that it also has origins in the society we have constructed. For hard-nosed reductionist biologists, sniffing around the causes of obesity outside the laboratory is most unattractive because it brings us into the world of psychology, of human behaviour and of social organisation and these are all seen as “soft sciences”. If this view persists, then the so-called ‘hard sciences” of genetics and its associated disciplines, will wane in importance. Consider the brouhaha that greeted the discovery of cafeteria feeding of rats to induce obesity, the discovery of genetically obese rodent models, the incredible discovery of the appetite regulating plasma protein leptin and now, the flavour of the month, the gut microbiota. All have hit the front covers of Nature and Science and all have been the flavour of the months at key scientific conferences. But when all of these are added up, the best they can do is explain bits and pieces of the “how” of obesity. They cannot some of the “why” such as genetic predisposition but they cannot explain the “why” of individual obesity and overweight.

What makes humans so different from other species is that we alone have mastered the ability to learn from one another by imitation. This imitation can be vertical such as what we learn from our parents. It can be horizontal such as what we see others doing. Of course, we actually don’t have to see others doing something to imitate it. A third party can describe what he or she saw and we can have a shot at it, maybe getting it right first time, maybe having to go back for another look at the person who has mastered this act and eventually, we will be able to do it. These acts of imitation spread through society at a rate vastly greater than that of natural selection of genetic potential. To the biological scientist, this is interesting but seriously wooly. It is poorly defined, poorly characterised, impossible to measure and impossible to attribute origins of imitated acts.

In 1976, Richard Dawkins wrote a book which to this day remains a best seller entitled the ‘Selfish Gene’. Dawkins did not mean that there was a gene for selfishness but rather that all genes were utterly selfish in competing with other genes to be included in the blue print of the next generation, the one after that and so on. The human body is the vehicle and the gene is the “replicator”. But Dawkins stepped boldly out of biology in coining the term ‘meme” to explain the basic unit that is involved in the vertical and horizontal transmission of human knowledge. The exact quote is thus: “ We need a name for a new replicator, a noun that conveys the idea of a unit of cultural transmission, or a unit of imitation. ‘Mimeme’ comes from a suitable Greek root, but I want  a monosyllable that sounds a bit like ‘gene’. I hope my classicist friends will forgive me if I abbreviate mimeme to meme^[1]”.

A meme is any concept or idea that is replicated by imitation. It can be verbal (rote, word-of-mouth, sung or chanted), written (prose, verse or music) and it can be an action (the Maori Haka, the handshake, the Christian blessing). The private thoughts and fantasies you have lying in bed or day dreaming on the bus to work are not memes since there is no expectation of transmission to others. Dawkins saw memes as being identical to genes in their characteristics with the three prerequisites of the latter: replication, variation and selection. Memes compete with one another for retention within our brains and there are far more meme than there is storage space in our brains  for them so the memes that win out to to be transmitted  vertically are no different from the genes that win out for retention in the next generation.

The development of obesity is a passive event over time since nobody really sets out to gain weight. But once we gain weight, we access memes that are implanted in our brains: “Fat isn’t pretty”; “Being fat is bad for health”. But when it comes down to the decision to “do something”, what is the behaviour we imitate? For some, especially among young professionals, the imitated behaviour fights the passive gain in weight, a life-time commitment of watching and weighing, of eating carefully and of exercising diligently. This behaviour is also true for some who lost weight and who want to imitate that behaviour that retains weight loss. For others, and it is a fact of life that it is the majority, the imitated behaviour is to do nothing. The meme to do something about overweight has to compete with memes that govern other activities in daily life and the modeled meme is one of the status quo. Fat people don’t die on the streets. They grow old. They are no sadder and no happier, no poorer and no richer and no more loved or feared than lean people.

The future of cell biology will reside in the cell since the latter is the raison d'être of cell biology. Human obesity can be studied by the geneticists and the memeticists on different planets as is presently the case. Those who bring these disciplines together will be the future. Memes are neither angels nor demons, which flit around some unique ethereal space entering our head for good or bad. Memes are ultimately connected to a neuronal network in the brain, unique to that meme. Thus they do have a biological base but not a genetic base. The biological base must connect to the phenotype. I wish I could sing like the late Luciano Pavarotti or swing my golf club like Tiger woods but I cant. Why not? I can cut the grass and I’m good at figuring out complex scientific concepts and at designing experiments to test these theories. Why so? Is our phenotype where our genotype meets our ‘memotype’? Complex questions indeed but valid complex questions.

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^[1] For those of you who would like a quick tour of memes, try the review by McNamara in Frontiers of Evolutionary Neuroscience May 2011 (volume 3): “Can we measure memes”. For a truly fantastic introduction to memes, buy Susan Blackmore’s book “the Meme Machine”, Oxford University Press.