The year 1956 stands out in my mind for a variety of reasons, the most important being (at least for me) that it was the year I was born. It also marked the year of the only ‘perfect game’ even thrown in a baseball World Series. Music fans might remember that it was the year that Elvis Presley entered the United States music charts for the first time, with 'Heartbreak Hotel.'

1956 was also the year a scientist named Roger Williams published a book called Biochemical Individuality, which attempted to relate inherited individual distinctions to nutritional requirements. Although Williams was no small figure in medicine (at the University of Austin he had discovered pantothenic acid, one of the critical B vitamins, and had published skews of articles detailing some of the most basic biochemical discoveries) Biochemical Individuality attracted little, if any attention from the medical community, probably due to the fact, as Jeffrey Bland speculates in his book Genetic Nutritioneering, Williams expressed many of his ideas in biochemical terms, which doctors of the time were far less comfortable with compared with today.

How prescient is the following phrase:

“The existence in every human being of a vast array of attributes which are potentially measurable (whether by present methods or not), and often uncorrelated mathematically, makes quite tenable the hypothesis that practically every human being is a deviate in some respects.”

It’s a strange choice of words, but the word deviate in this context signifies a turning away from the normal or a variance of some sort. Of course, we tend to think of the word more as a term for individuals who deviate from some sort of social norm; but norms are norms.

Williams was certainly deviating from conventional medical wisdom. Nobody at the time was looking at peculiar and individual aspects of nutrition that might be predicted genetically. More importantly, in 1956 there wasn’t anywhere near the enormous genetic industry and technology that exists today; it had only been three years before that James Watson and Francis Crick deduced the basic structure of DNA, (Deoxyribonucleic acid) –the double helix-- that contains the genetic instructions specifying the biological development of all cellular forms of life.

Thus when Williams talked of “attributes that are potentially measurable (by present methods or not)” he is taking an amazingly huge step into the future.

So Williams’ phrase “often uncorrelated mathematically” should probably be reinterpreted to mean “we can’t see the connections because of our current puny computational abilities.” Nowadays we link supercomputers together into vast neural networks and process data at a speed and accuracy that just boggles the mind. It was just this type of muscular computing that allowed scientists like Craig Venter and his firm Celera Genomics to help crack the human genome in record time. Today, the combination of gene sequencing and supercomputers is a day to day event in hundreds of laboratories worldwide, and is a prime part of a vast new field called bioinformatics.

In 1956, nutrition science was still in its infancy, concerned mostly with deficiency types of diseases such as pellagra and anemia, and making sure that we all ate “balanced meals.” There was no link between diet and cholesterol or between cholesterol and hardening of the arteries and medical journals often featured cigarette ads on their back pages. Ulcers were often treated by telling the patient to drink copious amounts of milk, the so-called “sippy-diet.” In other words, nutritional thinking at the time was predominantly disease-based, which is odd, since almost everything we do with food has absolutely nothing to do with disease. This resulted in what my friend and colleague Jonathan Wright used to call "The Association Diets.'

This is not to say that pieces of the puzzle weren’t evident, or that intelligent people were not already beginning to ask the right questions. It’s just that the questions could only be based on what was thought to be known, and what was known was not very much.

I can remember taking a computer class in high school (already well into the 1960’s) where we were taught to diligently inscribe a series punch cards with a 'number 2' pencil, which were then collated and fed to a machine the size of a large refrigerator, which then hacked and coughed for a while, finally yielding a half page printout of a list of fifty prime numbers.

Unless, of course, you had the misfortune to have penciled in the wrong box, in which case you just started all over again; a frustrating experience, which lead to one of my young colleagues, in a rage of frustration, placing one of the cards on the floor and proceeding to stomp on it repeatedly with his shoed foot, sending it on to the card reader --and probably producing the first computer virus-- a trick many of us would repeat when similarly frustrated. Your home computer can do these functions in micro-seconds, and the software to do it is considered so basic that it is usually packaged for free with the operating system.

I received an interesting question from my Facebook Page.

Thanks for providing an awesome guide in the Genotype Diet. Been practicing it as best I can for about 7 months and feel powerful. (I'm also doing good vitamins which is definitely part of the reason I feel really good.)

When I talk to people about the Genotype Diet and the benefits I've achieved from it, the main question I get is: Exactly what research has determined the genotypes, and the superfoods/toxic foods in the book? I can't begin to answer that question as I don't recall seeing it addressed in the book or on the website.

I'd love to learn more about the types of tests that you did to determine which people are in what genotypes as well as which foods are in which categories, per type.

This is a great question, but given that the best 'scientific answer' would be to show you the data tables and computer source code I can only try to explain a bit of the process. The problem with mass-market books is that you can only provide the upper-most level of information and a simplified version of that to boot, so I understand.

What I term the 'genotypes' (really 'epigenotypes' or 'morphotypes' but try to get a publisher to agree to use these words) are semi-synthetic constructs involving a stepwise statistical analysis of variation. They stem from the phenotypic (real world) characterizations reported for the ABO groups, Rh, secretor and additional biometric markers (D2-D4, fingerprints, etc). The idea was to look for pleiotropic (sympathetic) relationships between the multi-dimensional genotype/ phenotype data, especially if they are known to exert their effects through transgenerational actions. Using multivariate analysis we then look to see how the data separates or groups together. Since, with the exception of secretor, taster, Rh and ABO, we're looking at phenotype, I felt very comfortable including data from other, traditional typing systems (Ayurveda, TCM) which were also based of physical traits.

The base data includes virtually all published scientific tabular data on variations in physiology and pathology associated with these parameters, in addition to our own profiles of roughly 3,000+ additional people. At that point the data was filtered according to degrees of three basic metabolic 'biases': 'thriftiness' (metabolic compromise), 'receptorism' (immune tolerance) and 'reactance' (auto-immunity).

The genotypes are not 'perfect' typologies (every Explorer does not look or act exactly as every other Explorer) because we cannot possibly encapsulate all variation in everybody. Two families using the same set of blueprints will most likely build two different houses, due to differing financial constraints, choice of land plot, etc. Most of the time and given the tools we might encapsulate 30-50 percent of the data variation (principal components) in any one person and what we encapsulate in one might be slightly different than what we get for another. In statistical terms this is called 'multiple inclusion criteria' and it is a keynote of factor analysis or 'fuzzy logic.'

What results are six basic 'types' that with considerable tweaking encapsulate an acceptable amount of variation. Crunching the system into six types and cramming them into a hard-coded 'book' is much less effective than dynamically generating one-to-one diets in software, but it is still a pretty good approximation of some basic phenotypic variation and is more helpful than not.

Once we get here, the next step was to match the expected physical manifestations to a large database of foods that I've been collecting for the last two decades. For each food, this database contains about 300 individual values (gluten content, vitamin A, known allergen, etc.) At this point a second set of algorithms takes over and each food is evaluated constituent-wise based on a weighed value system much like a lawyer might argue a case in court. For example, evidence of developmental instability or constrained growth (differences between left/right sides of body, certain fingerprints, short leg length) might result in limiting foods that cause excess glycation.

If no negative attributes (for example, if the food contains a lectin or is known to encourage bacteria overgrowth, etc) is recorded, then the next step is to see if a case can be built for the food having any specialized benefit (for example, sardines might become a superfood if increasing the amount of RNA nucleotides is desirable; artichokes because they encourage probiotic growth in a strain of bacteria known to be good for a certain blood type). Lacking either of these elements, the food is simply labeled 'food' and considered more or less neutral.

In the simple case of rice versus rice milk it is most likely additional gums in the milk that are the issue. Certain gums amplify the effects of problematic proteins in other foods.

http://www.drpeterjdadamo.com/wiki/wiki.pl/Lectins

People also ask a lot about peanut oil versus peanuts or cherries versus cherry juice. Usually it is a difference between one form that contains some sort of problematic protein versus the other that doesn't. Also, occasionally in the Genotype diet (unlike the BTD) with complex foods, sometimes one nutrient influences the value of another which alters the value of the food.

Here are blogs of mine tagged as 'genotype diet.' You will see some elements of the process discussed in detail in many of these entries.

http://www.dadamo.com/B2blogs/blogs/index.php/genotype-diet/?blog=24

I've spent the beginning of this New Year cleaning up the various sites that I administer. In finishing up work on the genomic wiki-like knowledge base that we built several years ago, I thought it might be helpful to suggest 25 of what I feel are the best articles on The Individualist.

These are not exactly 'consumer level' stuff; more likely it would be called 'pro-sumer level' and I recommend these articles for those die-hards who just have to know everything. If you are still trying to figure out what to do with spelt, tofu or agave syrup, you may want to wait a while before tackling them.

1. ABH Antigens
2. A-like Tumor Antigens
3. ABO Blood Group
4. ABO and Secretor Genetics
5. Agglutination
6. Blood and Anthropology
7. Biology of Carbohydrates
8. Chromosome 9q34
9. Disease and Blood Groups
10. Epigenetics
11. Founder Effect
12. Genes and Environment
13. Glycation
14. Glycolipids
15. Glycoproteins
16. Joseph Charles Aub
17. Lamarckism Revisited
18. Lectins
19. Lectins Resist Digestion
20. Lectins and the Intestines
21. DNA Methylation
22. Phenotypic Plasticity
23. Polyamines
24. Secretor Status
25. Stress Blood Groups

More 'damned data' (Charles Fort's words, not mine): studies from the scientific literature which could pass for some of the more outlandish statements in The GenoType Diet:

The phenotype of an individual is the result of complex interactions between genotype, epigenome and current, past and ancestral environment, leading to lifelong remodelling of our epigenomes. Various replication-dependent and -independent epigenetic mechanisms are involved in developmental programming, lifelong stochastic and environmental deteriorations, circadian deteriorations, and transgenerational effects. Several types of sequences can be targets of a host of environmental factors and can be associated with specific epigenetic signatures and patterns of gene expression. Depending on the nature and intensity of the insult, the critical spatiotemporal windows and developmental or lifelong processes involved, these epigenetic alterations can lead to permanent changes in tissue and organ structure and function, or to reversible changes using appropriate epigenetic tools. Given several encouraging trials, prevention and therapy of age- and lifestyle-related diseases by individualised tailoring of optimal epigenetic diets or drugs are conceivable. However, these interventions will require intense efforts to unravel the complexity of these epigenetic, genetic and environment interactions and to evaluate their potential reversibility with minimal side effects.

Nutri-epigenomics: lifelong remodelling of our epigenomes by nutritional and metabolic factors and beyond. Clin Chem Lab Med. 2007;45(3):321-7

Epigenomics or epigenetics refers to the modification of DNA that can influence the phenotype through changing gene expression without altering the nucleotide sequence of the DNA. Two examples are methylation of DNA and acetylation of the histone DNA-binding proteins. Dietary components - both nutrients and nonnutrients - can influence these epigenetic events, altering genetic expression and potentially modifying disease risk. Some of these epigenetic changes appear to be heritable. Understanding the role that diet and nutrition play in modifying genetic expression is complex given the range of food choices, the diversity of nutrient intakes, the individual differences in genetic backgrounds and intestinal physiological environments where food is metabolized, as well as the impact on and acceptance of new technologies by consumers.

Epigenomics and nutrition. Forum Nutr. 2007;60:31-41.

Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, such as broccoli and broccoli sprouts. This anticarcinogen was first identified as a potent inducer of Phase 2 detoxification enzymes, but evidence is mounting that SFN also acts through epigenetic mechanisms. SFN has been shown to inhibit histone deacetylase (HDAC) activity in human colon and prostate cancer lines, with an increase in global and local histone acetylation status, such as on the promoter regions of P21 and bax genes. SFN also inhibited the growth of prostate cancer xenografts and spontaneous intestinal polyps in mouse models, with evidence for altered histone acetylation and HDAC activities in vivo. In human subjects, a single ingestion of 68 g broccoli sprouts inhibited HDAC activity in circulating peripheral blood mononuclear cells 3-6 h after consumption, with concomitant induction of histone H3 and H4 acetylation. These findings provide evidence that one mechanism of cancer chemoprevention by SFN is via epigenetic changes associated with inhibition of HDAC activity. Other dietary agents such as butyrate, biotin, lipoic acid, garlic organosulfur compounds, and metabolites of vitamin E have structural features compatible with HDAC inhibition. The ability of dietary compounds to de-repress epigenetically silenced genes in cancer cells, and to activate these genes in normal cells, has important implications for cancer prevention and therapy. In a broader context, there is growing interest in dietary HDAC inhibitors and their impact on epigenetic mechanisms affecting other chronic conditions, such as cardiovascular disease, neurodegeneration and aging.

Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol. 2007 Oct;17(5):363-9. Epub 2007 May 5

The purpose of this paper was to selectively review the literature on the role of epigenetics in mental illnesses. Aberrant epigenetic regulation has been clearly implicated in the aetiology of some human illnesses. In recent years a growing body of evidence has highlighted the possibility that epigenetics may also play a key role in the origins and expression of mental disorders. Epigenetic phenomena may help explain some of the complexity of mental illnesses and provide a basis for discovering novel pharmacological targets to treat these disorders.

Role of epigenetics in mental disorders. Aust N Z J Psychiatry. 2008 Feb;42(2):97-107.

A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B(12) and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes.

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19351-6. Epub 2007 Nov

Major efforts have been directed towards the identification of genetic mutations, their use as biomarkers, and the understanding of their consequences on human health and well-being. There is an emerging interest, however, in the possibility that environmentally-induced changes at levels other than the genetic information could have long-lasting consequences as well. This review summarises our current knowledge of how the environment, nutrition, and ageing affect the way mammalian genes are organised and transcribed, without changes in the underlying DNA sequence. Admittedly, the link between environment and epigenetics remains largely to be explored. However, recent studies indicate that environmental factors and diet can perturb the way genes are controlled by DNA methylation and covalent histone modifications. Unexpectedly, and not unlike genetic mutations, aberrant epigenetic alterations and their phenotypic effects can sometimes be passed on to the next generation.

Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res. 2006 Aug 30;600(1-2):46-57. Epub 2006 Jul 18

Had a rather relaxing week in Jamaica. Beautiful weather and friendly people. It was nice to just sit around a pool and read something besides computer or medical textbooks. I confined my reading to mostly ancient history.

Since being back I've be messing around with Facebook, the social networking website that everybody seems to be on nowadays. I think it is much better than MySpace, since it does not allow you to alter the appearance of your pages all that much. I always found MySpace rather unsettling, what with all the blaring colors, poor quality videos and music on people's sites: most of which I prefer not to see nor hear.

When Facebook does allow you alter stuff, it is mostly in the form of applications ('Facebook Aps') which run inside of Facebook. Programming these applications can be perplexing, since Facebook uses may proprietary pseudo-languages and interfaces -and the documentation can be spare at times.

If anyone has been to my Facebook page recently, they'll already know this, but for those who have not, my first application called 'Is it right for your blood type?' is now up and running.

Here is the link

Of course, you'll have to be on Facebook to use it, but they make it very easy to join and it is a rather safe place overall.

The app is based on the TypeBase Program on this website, but also allowing you to search by foods (soy, celery, beef, etc.). You can add the app to your profile sidebar which then allows others to join and use it as well.

Like golf, learning new computer languages is occasioned by a rather irksome awkward stage, but I think I'm finally heading out of it. if you do use the app and find a bug please drop me a line and let me know.

In addition to the Facebook work this morning was spent doing a half-hour interview for Singapore radio with a charming young host. While on the radio I opened some recent mail and was pleased to receive three spanking new copies of the 'Allergies' book, which has just been translated into Arabic. It is wonderful to marvel at just how global this eating philosophy has become.