Electronic circuits spend a lot of their time filtering out noise, and many motifs in molecular biology do this same function. Most of this noise is stochastic: a charmingly ancient Greek word that more-or-less equates to random, but not exactly, being derived from the Greek stochastikos, ‘skillful in aiming.’ To me, stochastic embodies the old saw that ‘if something can happen, it will.’

Stochastic occurrences mess up our pretty, deterministic, view of how things happen. For example, the response of our bodies to radiation therapy is stochastic since not every cell receiving the radiation energy is at a point in its life cycle when the radiation therapy can effect it: Some cells are (those currently reproducing) whilst other cells are not (those currently at rest). This is a problem when one uses methods of measurement that are Gaussian (i.e they ‘average things out’) because these types of measurement will yield indications of a more gradated response than really occurred.

Stochastic music was pioneered by the composer Iannis Xenakis. Unfortunately, while undoubtedly making for interesting math, I agree with this author that the music sounds more or less like an hour-long extended visit to a junk yard. I do like some of Xenakis’ other music though, such as Metastaseis..

Stochastic versus graded response.

Most network motifs try to soften up the responsiveness of transcription factors to stimulus with a high signal to noise ratio, sort of like how an experienced parent can tell the difference between a crying child who just needs to nap versus a child in true distress.

Since developing the Quodlibet module in Datapunk I’ve been increasingly aware of the need to incorporate these types of motifs in my network calculations, when and where they show up. Quodlibet currently does quite a bit of graph/network/combinatorial calculation already (click on the Analytics link in any molecular map to see it at work) so looking for network motifs seemed the logical next step.

I mostly work in Perl, so I often take advantage of CPAN (The Comprehensive Perl Archive Network) which hosts a wealth of Perl modules, including a terrific collection of bioscience libraries, such as Bioperl. These modules are what makes Perl so great: you do not have to reinvent the wheel and in many instances you don’t even have to know exactly how the wheel works. Just plug it in, feed it good stuff and get the output. CPAN has been a great asset with Quodlibet, but contained no modules for network motif detection. Fortunately an online homework assignment provided me with the means to get started.

However, before I launch into any of that stuff, in my next blog I’ll take a look at the most common network motifs. These have been identified largely through the work of Uri Alon and his lab at the Weizmann Institute of Science in Israel, and if your interest runs in the direction of computational biology, I recommend that you take a look at his book Introduction to Systems Biology: Design Principles of Biologic Circuits (Chapman and Hall/CRC). The loop is a basic network motif, so next blog we’ll take take a look a a few variations to get an idea about how these things work things.

Like the digital circuitry in your computer, clusters of network motifs are capable of computational processes. Think about this: Humans share about 98% of their genome (at least the sequences) with apes. This of course begs the question ‘why are we not more similar?’ The answer is that while we share much of the base sequences, there are tremendous differences in the ‘computational knowledge’ that acts upon these sequences, in particular the networks involved in transcription factor regulation: operons, regulons and modulons. It is the ‘combinatoric wisdom’ that seems to differentiate between the classes of life forms.

It is not enough to be in the right place at the right time. You should also have an open mind at the right time. –Paul Erdos

One thing I’ve noticed about my work with blood groups, which has done much to convince me that it is truly valuable, is that fact that it seems to make a considerable number of conventional and alternative practitioners equally apoplectic.

Recently, on a Facebook group that I belong to, a participant asked the other members what they ‘thought about the Blood Type Diet’. I was surprised by the intellectual horizon of many the responders. It seemed that the practitioners who were skeptical of the theory had tried it once for a while, or had known or heard of of someone who had tried it unsuccessfully, and did not support its use for these or similar other reasons.

I had left this group a while back, after a particularly snarky attack from a Ayurvedic practitioner, who went to great lengths to prove that Ayurvedic classifications were superior; using, of course, himself as an example. As a blood type A, he tried to make the point that while a vegan, he was always sick, as if to prove that the type A diet is a vegan diet, which it is not.

It brought back to mind this quote from Sinclair Lewis:

It is difficult to get a man to understand something, when his salary depends upon his not understanding it.

This current discussion thread included a response from an acupuncturist and was quite typical of the more negative responses:

I don’t think its ready for prime time. Lectins in blood are not the whole story. When I eat as recommended for my blood type I get bloated and gain weight.

To me this brought up the question of what happens when we evaluate information simply and exclusively by whether we like or agree with it. Read any diet blog, pro or con something, and you’ll quickly see just how pervasive this is.

I wrote this response and thought I’d share it.

In any discussion one can expect a combination of facts, experiences and opinions. All are valid in their own way. Partial stories can be helpful as well.

Some basic facts: the digestive tract normally glycosylates in a manner influenced by age, diet, pathology, species, microbial load, ABO group and ABH secretor status. That is just basic glycobiology and this list of contributing factors is well-known.

The same is true in any scenario characterized by aberrant glycosylation, which in its own right, characterizes an extraordinary range of pathology: malignancy, inflammation, dysbiosis, and aging all show derangement in glycosylation. Indeed in most cases it is their preeminent phenotypic manifestation. So at its very minimum, as a member of this list, ABO/secretor is a partial predictor of all this. Aside from that a variety of phosphatases, brush border hydroxylases, and who knows how much of the microbiome is conditioned by ABO expression in the gut. Any PubMed search should suffice to prove the point.

Out of the box, the basic ABO-only diets developed for each blood group work in about 80% of the people who employ them. That percentage is from over 8000 case reports generated off of our main website from 1999-2003. Certainly not perfect, but then again what is?

Confirmation biases aside (and they are obviously there), the data showed one particularly interesting trend: the 80/20 percentage was consistent across the groups. In other words, 80% of the type Os claimed the diet was beneficial, as did 80% of the Bs, 80% of the As, etc. Now as anyone who has read even the basic book can tell you, the A diet looks nothing like the O diet. However 20% is obviously a large number of unhappy people, and it is entirely feasible that any given person can reside there. There can be a plethora of reasons why the the recommended diet for a blood type could fail, perhaps in the great majority of cases even for reasons that have nothing to do with blood type.

Although cheap as hell, a simple ABO is a still a pretty rudimentary approach and a second gene (FUT2) which controls one’s ability to ‘secrete’ their blood group substance in a free unbound form can be an important additional discriminant. Adding this to the mix does clean up the results a bit, especially by identifying the the so-called ‘nonsecretors’ who are genetically unable to secrete their blood group antigens in an unbound form. Interestingly enough, nonsecretors make up 20% of the population and the literature is rich in references to a variety of pathology issues linked to this outcome. But that is another story.

Now, what to do about experiences and opinions? They can be honored in their singular nature, but they don’t move the discussion very far. To a person who has gotten no results from acupuncture, homeopathy or Ayurveda, these are all useless things. But we all know that in larger data sets they can and do appear to help a great majority of people. Something doesn’t have to work in everyone, or every practitioner, to be useful.

Thanks for reading.

Take your everyday Super Bowl stadium.

Now multiple that by 48.

Although the post spends a lot time discussing the 20% who don’t respond to the basic ABO diet, let’s spend a few moments describing the societal effects of the 80% who apparently do. As of December 2011, my books have sold a total of approximately six million copies. Assuming that each book is used by one individual (a moderate estimate, since most purchasers seem to implement the program for other family members as well) and then subtracting 20% (1,200,000) from this number (assumed non-responders) yields about 4,800,000 individuals who may have theoretically benefited from changing their diet in this manner.

Let’s put a visual on this. Assume that the average Super Bowl audience is 100,000 fans. An aerial shot of the number of people who have benefited from this theory would have to include 48 fully-packed Super Bowl stadiums.

As Vladimir Lenin quipped, ‘Quantity has a quality all of its own.’

Although participating in these types of discussions is much like shoveling the stables of King Augeas, it made me think about how flippant we can be with our words and deeds and how much truth gets locked away in a vault of our own mind, simply because, as F. Scott Fitzgerald famously alluded, we failed the test of having the ability to hold two opposed ideas in mind at the same time and still retain the ability to function.

* BTW: Most common discovery about people who visit the forums on my main website and report that the diet did not work for them: They had their blood typed wrong or had remembered or been told incorrectly.

Initial hour of six-hour, day-long seminar done for the UB Nutrition Institute, October, 2011.

Peter D’Adamo, Flying Spines (1981)

Normally, your ordering department does a pretty good job of things and the supply of the constituent parts necessary to make a decent replacement window (one assumes these to be things like glass, vinyl, aluminum, hardware, etc.) arrive punctually and in sufficient amounts to allow you to make the maximum number of windows with the minimum amount of wastage.

However, over time changes in personnel lead to problems of supply and demand. Tired, jaded people in the ordering department forget a decimal point and you wind up with an excess of window locks; poorly-trained workers on the assembly line make a variety of newbie-type errors that result in windows that are unsellable. Over time this pile of unsellable windows begins to accumulate to the point where it begins to clog up the aisles, creating an unhealthy workplace. Soon the corporate bank account is drained due to excessive purchasing and the assembly area is choked with unusable, unsellable, windows. Workers begin to grumble about the unsafe working conditions and a few threaten to strike unless conditions improve. An investigation seems to indicate that your factory supervisor, Mr. Mtor, has a grudge against you due to his being passed up for a promotion at his last salary review and has been going around sabotaging things by telling the workers to not bother about quality control and cleaning up after themselves.

Concerned about the future of the family enterprise, you fire Mr. Mtor and hire a sharp graduate of Wharton School of Business and soon things begin to right themselves. A special work team is put together to go through the piles of unsellable windows, cannibalizing parts that can be reused to create properly constructed, sell-able windows. All new orders are now reviewed to insure that no duplication or excess inventory is allowed to siphon off precious capital and storage space. Soon conditions begin to improve, your workers seem much more happier, and productivity and profitability skyrocket.

Welcome to the wonderful world of cellular autophagy.

Autophagy (‘self-eating’) is a catabolic (breakdown) process used by cells to degrade and remove some of their internal components deemed to be unnecessary or undesirable. Like our window company, cells are little factories of a sort, and as such they function under many of the same dynamic considerations: Things accumulate; byproducts are produced that can’t do anything, etc.

In cells these byproducts are usually some sort of misshapen protein that folded in some manner incomprehensible to the cell and hence not usable. This is not all that uncommon and many common chronic diseases are characterized by the production of proteins that did not fold properly. Much like having a rock in your shoe, having misfolded proteins in the synthetic/secretory parts of the cell factory (an organelle called the endoplasmic reticulum) results in what is known as the unfolded protein response, a stress reaction to these weird proteins.

Eat them up yum yum.

This phenomenon is called ‘ER Stress’ and can result in either of two outcomes.

Try to fix things or at least spit it out: The response to the misfolded proteins can trigger molecules called chaperones that can attempt to fix/refold the proteins into something usable. Lacking this response, the cell can attempt to encapsulate the offending stuff, digest it, and then spit the capsule out. This is autophagy.

Failing that, call it quits: If things are so bad, sometimes the cell just calls it a day and commits at type of cellular hari-kari suicide called apoptosis.

In addition to acting as a type of cell cleansing mechanism, autophagy is a very old survival tool. Like a factory deprived of raw materials because of a transit site, cells deprived of nutrients will scrounge around the workplace looking under tables and behind cabinets for surplus parts. In the cell’s case, when deprived of nutrients like the amino acids tyrosine and methionine, the cell will begin to breakdown parts of itself to keep going. Much of the time, this breakdown is a good thing, and perhaps explains why things like calorie restriction seem to increase lifespan: under those conditions the cell is munching away at itself, and since it is no fool, a lot of what it munches away at is junk best gotten rid of anyway.

Autophagy is normally kept under control by a protein called MTOR that acts as a sensor for conditions that might require autophagy. Normally MTOR blocks autophagy, so when it is inhibited, autophagy strikes up the band. MTOR can get screwed up in cancer, which is not a great thing since autophagy tends to block the apoptosis suicide mechanism (why kill yourself when things are working this great?) This has led some to posit that enhancing autophagy might not be a great thing. However it is probably not this simple as other genes that act as tumor suppressors appear to enhance autophagy by blocking MTOR, so we still don’t know the complete answer on that one.

Two things for sure: autophagy looks like a winning strategy when it comes to neurodegenerative disease and aging. Slower aging associated with decreased MTOR activity, while disease like Parkinsons and Alzheimers are linked to blockages in autophagy.

Some natural products, including epigallocatechin gallate (EGCG), caffeine, curcumin, and resveratrol, have also been reported to inhibit MTOR when applied to isolated cells in culture. More work is needed to see if these work at the level of dietary supplementation.

There are sugars,and then there are sugars.

One interesting agent with well-recognized effects on autophagy is the natural disaccharide sugar trehalose, a sugar produced by bonding two glucose molecules together in a way that differs significantly from the sugar on top of a jelly donut. Trehalose is found in many organisms, including bacteria, yeast, fungi, insects, invertebrates, and plants. It functions to protect the integrity of the cell against various environmental stresses like heat, cold, desiccation, dehydration, and oxidation by preventing the screwing-up of the cell’s protein insides.

Extracting trehalose used to be a difficult and costly process, but recently an inexpensive extraction technology has allowed for its use in a broad spectrum of applications. Trehalose prevents cells from dehydrating, a phenomena that disrupts much of the cell’s insides in way that are not reparable. Trehalose-treated cells seem to resist this because the trehalose ‘splints’ their guts in place, so that when the cells get a chance to rehydrate they come back good-as-new. Dehydrated cells are common with aging, as the aging process tends to thin out the cell membrane, making it harder and harder for the cell to maintain its internal water balance.

Trehalose has been accepted as a novel food ingredient under the GRAS terms in the U.S. and the EU. Trehalose has also found commercial application as a food ingredient. It is available in dietary supplement form.

Maybe the most interesting property of trehalose is its ability to enhance autophagy. Neurofibrillary tangle (NFT) is a characteristic hallmark of Alzheimer’s disease. The accumulation of a protein called tau in the NFTs is one of the characteristic features of several diseases known as tauopathies. In cell culture studies trehalose treatment exhibited significantly decreased level of tau in all tau species.

What is especially interesting about trehalose is that it works in ways that are independent of the MTOR protein, leaving it free to do its work as a sensor of changing environmental conditions.

Turns out we didn’t have to fire Mr. Mtor after all.

The more technically inclined, with an up-to-date modern browser, may want to check out the autophagy network map in Quodlibet.

1. Kim SI, Lee WK, Kang SS, Lee SY, Jeong MJ, Lee HJ, Kim SS, Johnson GV, Chun W. Suppression of autophagy and activation of glycogen synthase kinase 3beta facilitate the aggregate formation of tau. Korean J Physiol Pharmacol. 2011 Apr;15(2):107-14. Epub 2011 Apr 30. PUBMED
2. Rodríguez-Navarro JA, Rodríguez L, Casarejos MJ, Solano RM, Gómez A, Perucho J, Cuervo AM, García de Yébenes J, Mena MA.Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation. Neurobiol Dis. 2010 Sep;39(3):423-38. Epub 2010 May 28. PUBMED
3. Sarkar S, Davies JE, Huang Z, Tunnacliffe A, Rubinsztein DC. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein.J Biol Chem. 2007 Feb 23;282(8):5641-52. Epub 2006 Dec 20. PUBMED
4. Krüger U, Wang Y, Kumar S, Mandelkow EM. Autophagic degradation of tau in primary neurons and its enhancement by trehalose. Neurobiol Aging. 2011 Dec 12. [Epub ahead of print] PUBMED

Quodlibet (QUOD) is a suite of network creation, editing and querying software I am currenty developing. QUOD is a software application that displays biochemical pathway data in a way that is interactive and information intensive.

In addition to providing information about genetic-protein interactions QUOD also allows for additional information to be harvested, including data on the effects of natural products on gene-protein expression.

A bit of the Adipocytikine network as displayed in QUOD. Amber nodes indicate high betweenness centrality and in-degree. Dark green tags indicate that a natural product has been associated with the regulation of that node.

Unlike most biochemical pathway/network depiction programs QUOD actually ‘thinks’ in a social network sense in that it analyzes the network and reports on many graph functions including betweeness centralities, page-ranks, and cluster coefficients. This allows an immediate understand of which nodes are acting in a critically important role in the network.

It was designed to be simple, easy to user and fun to edit and develop in. Because it is web-based, no special software is required, other than a modern browser and a decent Internet connection. QUOD runs under the DataPunk platform and is open-access. Curators can use the extensive editing tools to add to, alter, or create entirely new networks.

One of the more powerful aspects of QUODLIBET is its ability to highlight naturopathic procedures and agents that have been shown to exert an influence on the expression or function of elements in a molecular network.  This will have a major influence on the future practice of Generative Medicine, since complex patterns of relationships between naturopathic agents and procedures (traditional as well as biomedical) can be superimposed over the network analysis of complex molecular graphs so as to allow clinicians to derive extraordinarily high quality suggestions about specific approaches that may more closely approximate the holism of the Vis Medicatrix Naturae.

Since the project is community-based, we are always looking for volunteers who are interested in helping out. Volunteers need not have any medical or super computer skills, just a passion for exactitude and a desire learn more about the genetics and biology. To learn more about QUODLIBET, you can download the User Guide and visit the Community Forums.

What is needed now is the community of volunteers who would be willing to devote time to curate additional maps. Hopefully this call to action will not prove too disappointing: I can think of no better way to enhance one’s own understanding and knowledge about a complex topic than to build mind-maps. Thus it is to the students of our profession that I direct this challenge, though any interested party with a computer and a decent Internet connection is welcome to help out.

Phase I of our map development program will involve translating the KEGG genomic and metabolic maps into QUOD format. KEGG maps are good and even hyperlink to relevant KEGG entries for enzyme activities, drugs, etc. However KEGG maps are hand drawn and cannot perform network graph computations. However KEGG has done much of the heavy lifting: converting a KEGG map to a QUOD map makes development quick and painless. From there QUOD will link all subsequent maps into clustered networks, allowing for greater and greater information processing.

The commonality between science and art is in trying to see profoundly – to develop strategies of seeing and showing. –Edward Tufte

One of the main goals of our Datapunk bioinformatics platform is the development of new and exciting information visualization (InfoViz) tools that can be used to develop new appreciations for the relationships between data. We are currently developing two new InfoViz platofrms that I think have great potential. But more than that, these tools feature stunning interfaces that go a long way towards again proving the fact that information, presented imaginatively, can not only yield amazing secrets, but can be stunningly beautiful as well.

Pathscrubber

The first InfoViz platform we developed is a full-bodied genomic network depictor called PathScrubber, which runs inside Datapunk. PathScrubber draws network graphs of gene-protein relationships. Each node in the network is click-able and links to a popup that provides information on that gene, through an API to OMIM (Online Mendellian Inheritance in Man). Perhaps more significantly, Datapunk is the first informatics tool that is harvesting scientific references detailing phytochemicals and dietary agents that have been reported in the literature to influence the expression of these gene-proteins.

PathScrubber.

Simply enter any gene-protein terms you wish to include in your network. Don’t worry about partial terms; PathScrubber will return a list of possible terms for you to consider and you can check which ones are appropriate in the next screen. After the program draws the network, you can zoom in or out with either the mouse or via a slider. Nodes containing genomic expression information on phytochemical or dietary agents are coded orange. PathScrubber has an extensive help page. PathScrubber is programmed in Perl, utilizing Léon Brocard’s GraphViz module to draw the graphs.

InfoViz Democratizers

This platform is designed to provide a venue to allow naturopathic physicians and researchers to animate their own data. One of the most exciting/important things we are developing is a set of guidelines for authors on how to structure their data so as to allow us to easily port it into a stunning visual display. Most JavaScript data is encoded in a format called JSON, which although paradoxically designed to be easily readable by humans when compared to other data structures, requires a heavy degree of ‘nesting’ of the data, which most non-programmers would find confusing and thus increase their proneness to data entry error. So we developed a simple language that only requires that the data be entered in a simple text file with a few codes. This is then parsed by Perl into JSON and piped to the page as HTML. Here are two examples:

Lectins: Classification and Taxonomy
Our second infoviz tool is a depiction of a the taxonomy and classification of known animal, plant and microbial lectins. Lectins are protein molecules that attach to sugars and modulate a variety of cell functions, including mitosis, agglutination, metastasis and infections. Most of the data for this infoviz is from my textbook, Fundamentals of Generative Medicine Clicking on a node should move the tree and center that node. This infoviz makes extensive use of JavaScript, especially the JavaScript InfoVis Toolkit. The tree-like structure opens and closes as one click on the various categories.

Lectin Classifications

Radio buttons on the top allow for the user to display the tree in different aspects and to chose between a ‘normal’ display, where the categories open up in a linear fashion of a ‘centering’ mode where the newly selected category moves to the center of the tree. Finally branches of the tree often contain hyperlinks to additional information.

Actions of Medicinal Plants
Our third infoviz tool is a depiction of a paper developed by Eric Yarnell, ND entitled ‘A Compendium Pharmacological Actions of Medicinal Plants and Their Constituents.’ Clicking on a node should move the tree and center that node. This InfoViz also makes extensive use of JavaScript, especially the JavaScript InfoVis Toolkit to display day in the form of a morphing hypertree. The centered node’s children are displayed in a relations list in the right column. The data set for this InfoViz is still in development.

Compendium of Medicinal Herbs

This rushed approach characterizes almost every encounter I’ve had with major media. They gobble up whatever simple facts there are so as to explain the gist of the story, then go looking for an opposing viewpoint so they can get off being held responsible for any direct conclusions. This is called ‘balanced journalism.’

The article usually begins with a roll call of all the famous people who are following or have been on the diet. I usually have never heard of any of these folks, but my daughters often serve to tell me a bit about who they are. Then the diets are described, but never fully. Some reporters concentrate on the lectin-blood group specificity, others the anthropology, some the digestive differences in physiology. However, I’ve never seen a single article explain all aspects to some degree, which is of course the strongest argument for the theory: That it can be verified in multiple dimensions of analysis.

On the positive side, many articles feature a personal story about an average-type person who has had success with the diet. Usually the focus is weight loss, for obvious reasons. Very few of these articles profile people who have been cured of any physical diseases by adopting this way of eating. Again, this is due to legal issues. However, trying to heal or control a physical illness is the most common reason why people try the blood type diets.

Hard Facts from the Fiction Department

Finally, and this is almost always rolled out at the end, the article presents one or two nutrition experts to pass judgement on the merit, risk and need to follow a diet for your blood type. Unless the expert has had some exposure to the deeper, scientific basis for the theory (never) their comments are almost universally negative.

These comments usually fall into common categories:

• The diets are dangerous. This statement is usually proffered by experts concerned that, by restricting certain foods by blood type, people will develop nutrient deficiencies. However, each diet variant (A, O, B and AB) is a carefully engineered balance of foods that ensures full nutritional value. This criticism has a long and hallowed record of institutional whoring for agribusiness: ‘whole grains are fine, except if you are gluten sensitive’, ‘high fructose corn syrup can be part of a balanced healthy diet’, etc. Curiously, this concern is often matched with the next:
• Of course people get better, the diets are all healthy: If you tell someone to get off of diet soda, they will feel better. I actually have no problem owning this criticism. We do include a lot of good naturopathic food wisdom with the blood type recommendations. I fail to see the problem with that. Paradoxically, if one were to go back and read my earliest popular book, Eat Right For Your Type they would find perhaps some of the earliest references to the value of using grass-fed beef, spelt and sprouted breads, quinoa and amaranth grains and a host of other weird foods. Now these are all part of the popular culture, but back then nobody recommended these things. I’ve always thought that the basic benefit of using blood type as a guide to proper eating was its ability to let people know exactly which, of all the supposedly healthy diets, would be best for them.
• There is no scientific validation. This criticism is particularly nefarious, since it says one thing but means another. To say that the blood type diet theory has not been tested in large numbers, via a double-blind study, at some neutral university, is in fact true. There are reasons why this has not occurred. One is the sheer size and cost of a study of this sort. Food and diet studies are notoriously difficult to control, require constant supervision, often must be pursed for years, and are enormously expensive. Now, on top of all that, multiply the work and expense by four. But let’s talk about what this criticism actually means. Most of the time what the critic is really implying is that the theory has no scientific basis, which is a form of intellectual dishonesty, since not one of theses critics has ever taken the time to read through the extensive collation of existing research, much of it freely available online, that supports the conclusions drawn to form the basis of the blood type diet. I don’t spend a lot of time writing critiques of other diet theories, but if I was planning to do so, I’d probably pick up the phone, call the other guy, explain my concerns and see if I’d gotten my facts straight. Yet in the last fifteen years I’ve never received any such phone call.
• This is pseudoscience. This pejorative term is often used in conventional science to tar and feather ideas and practices that have no basis in accepted science, such as a theory that flouts the basic laws of physics. Of course, one man’s pseudoscience is another man’s frontier science, but that is the continual rub of forward progress and most honest scientists agree that it is part of the game. However, usage of the term has increasing become a favorite tactic of scoundrels to manufacture disinformation and stop interest and inquiry into a topic they might detest for any number of non-scientific reasons. By the way, there is nothing in the theory behind eating for your blood type that flouts the laws of physics, chemistry, immunology or physiology. On the contrary, that’s the problem: To talk intelligently about it requires that you know more than a little about these disciplines.

Case History

My office was recently contacted by Alexia Elejalde-Ruiz, a young reporter for the Chicago Tribune and told that they were doing an article on the blood type diet. Having given literally hundreds, if not thousands, of interviews at this point, my PR person usually begins the process with a few questions, such as what prompted the interest. In this case the interest appeared to stem from the health editor, who is apparently a type O vegan and somewhat distraught by the conclusions drawn from my theories. However the reporter was respectful and several emails went back and forth with the aim of addressing concerns from some of the nutrition experts. Since some were quite technical we directed the reporter to various links that discussed those point in detail. However, none of our corrections were turned into teaching points (for example, ‘a lot of people often think this about the diet, but in fact..’). Instead it seemed that they just went down their list to the next concern.

My Spidey senses were tingling, and I suspected that the article already had a preconceived agenda. Not surprisingly, when released the article pretty much went out of its way to diss the entire concept. Because of an association with Gannett Publishing, this article has appeared in other publications as well.

Famously, one of the experts firing the dreaded Parthian Shot, a Michael Greger, MD, who is touted as the head of something called NutritionFacts.org, was quoted as the following:

Dr. Michael Greger, founder of NutritionFacts.org, said the premise of the blood-type diet is wrong: The blood-type system, which predates humans, is far more complicated than just ABO, he said. “People crave individualized, personalized science, but this is pseudoscience,” said Greger, a general practitioner specializing in clinical nutrition.

I will not dwell on the stupendously ignorant basis of Dr. Greger’s criticism, since it betrays a complete lack of understanding about how blood types function in the body. You can read my answer to a similarly uninformed vegan doc here. What is interesting is the use of the pseudoscience label. Not simply because it is being applied by a person ignorant in the basic science, but rather because a quick look at Dr. Greger’s website (veganmd.org) and his ostensibly important job as head of the rather questionable nutrititionfacts.org show instead a vegan-biased, rather jaundiced army of one, and certainly not the vaunted expert the Tribune article purports him to be. Although I certainly acknowledge the value of vegan diets for some people (but certainly not everyone) others argue that the vegan diet theory itself is a pseudoscience, hence the title of this blog.

Conclusions, if any.

Media profilers of science and health need to start vetting their so-called experts. Here’s a news flash: Many critics of diet books have their own diet books and dietary agendas to protect. You’d think as professional news media this would cross their minds, but apparently it doesn’t. Balanced journalism should not mean that you just go out and find someone to disagree with the premise of your coverage.

That if the crab dies
entirely in its totality
with it we all die
for all of eternity

Miguel de Unamuno, ‘The Immortality of the Crab’

Why does Dr. D recommend chemo for cancer? Seems like a primitive approach, and not in line with the Hippocratic Oath.

First of all, the Hippocratic notion of ‘first do no harm’ (primum non nocere) is not an accurate interpretation. It is more accurately, ‘if at all possible, do no harm.’ i.e it is a heuristic, not an algorithm. If it were a law then draining a abscess or giving a B12 injection would be a violation.

I suspect this question came up because of a case I had written about in my book The GenoType Diet. It involved a man who was blood group A, FUT2 positive (secretor) and homozygous for blood group M (MM) that had a cancer known to have ‘A-like qualities’. Under these circumstances I have discovered that these individuals have a much more difficult time with things. There are a variety of reasons for this. This constellation of blood group genetics has a higher rate of multiple drug resistance (MDR). (1) There is evidence that the levels of p-glycoprotein (the carrier molecule that is part of the system) molecule that up to seven times more abundant in tissues of individuals who are blood group A, which may go along way towards explaining why it appears that type A’s with cancer who receive chemotherapy often do not have as beneficial an effect as the other blood types. Finally, blood group A appears to have lower circulating levels of anti-Tn (Thomsen-Freidenreich) antibodies. The Thomsen-Freidenreich (Tn) antigen (also known as is usually present on cell surfaces in a cryptic form covered by N-acetyl neuraminic acid moieties and released into circulation in many different cancers. (2) Thus it provides a means of cancer surveillance, and it is this function that is compromised in blood group A, probably because the Tn antigen shares some structural similarity with the group A antigen. The Tn antigen is currently under intense study as a possible site for a cancer vaccine. (3)

In this case, which is not all that uncommon, the patient had ‘shopped around’ until they found an oncologist who had recommended a very mild protocol. Upon consulting with me they were surprised that I had instead recommended that they seek the more aggressive alternative protocol.

Ocypode quadrata. Some crabs just look immeasurably perky.

I’m currently monitoring two brain cancer cases who are bucking the odds for long-term survival. In both cases they received convention treatment plus a tailored regimen from me. I doubt if they had received only one or the other that they would be alive today, though I am certain that some natural medicine gurus would have told them that this was all a big mistake. Trouble is, where are these guys when the patient comes back with the recurrence? I can tell you that they are no where in sight. That’s when they send in the assistant to tell you that ‘maybe it is time to do the chemotherapy.’

Here are some case histories from the front line of the naturopathic/conventional oncology interface:

Case History #1

Years ago I had a patient who had an early-stage testicular cancer. This cancer is 100% curable with chemotherapy. His wife, a massage therapist, was pushing that he go ‘completely natural.’   I politely explained that there were many, many options he could use to help control and optimize his results, but it would not be wise to forgo a treatment such as this, which was so reliably successful. They opted instead to do juice fasts and go elsewhere. Six months later they were back in my office, he riddled with metastasis, now taking that very same chemo to simply ‘debulk’ the cancer and help him survive a bit longer pain-free.

Case History #2

I treated a patient for a number of years who suffered from a rather uncommon combination of non-Hodgkin Lymphoma and Hodgkin Disease. It was though to be the result of Agent Orange exposure that occurred from the patient’s multiple tours of Vietnam while in the military. He received aggressive allopathic treatment from Sloan-Kettering, but was advised that the best one could hope for would be a rather short-lived reprise. We commenced some nutritional and botanical co-treatment, which none of the Sloan-Kettering physicians objected to. After two years disease-free it was clear that the patient had experienced an exceptional result. Frankly, although many people believe that conventional medicine has no interest in naturopathic type therapies, he was asked back to the hospital, and in his own words, ‘put in a large room filled with guys in white coats who wanted to know exactly what, how much and how long had I been taking these naturopathic things.’

Several years after that the patient, a life-long smoker, was diagnosed with bladder cancer. He was treated, with chemotherapy and with variable degrees of success by physicians at Johns Hopkins. The doctors here advised him that they would not treat him unless he stopped all naturopathic treatment, which he did. Eventually his bladder was removed and some metastatic spread was noted soon after that was thought to be from the non-Hodgkin Lymphoma He was placed on a series of Rituxan (Rituximab) injections and seemed to do well for a while. However, these eventually stopped working, the disease spread and at his final consult before being set up for hospice, when asked if there was anything left they could explore, was told that ‘maybe they should contact their naturopath and see if there was anything he could do.’

My take on things

A primitive approach, IMHO, is to base your decision on broad sweeping conclusions drawn from consumer reading material that limits your ability to decide what is the right thing to do then and there. Hopes, aesthetics and dreams are nice, but we must also deal with realities.

The goal of any good physician is simple: To get their patients from one side of the river over to the other. If it can be done exclusively with naturopathic modalities, so much the better. If in order to do that I need to combine modalities, well, that is part of the equation. If the only way that I would agree to ferry them across would be to require them to do only that which is acceptable to me I would not be much a ferryman, now would I?

A liability we physicians labor under is the delusion that our patients cannot get better without us and our methods. As soon as we let go of that we can participate in their improvement joyfully no matter from which direction it comes from.

1. Weinstein RS, Kuszak JR, Jakate SM, Lebovitz MD, Kluskens LF, Coon JS.ABO blood type predicts the cytolocalization of anti-P-glycoprotein monoclonal antibody reactivity in human colon and ureter.Hum Pathol. 1990 Sep;21(9):949-58.

2. Uhlenbruck G. The Thomsen-Friedenreich (TF) receptor: an old history with new mystery. Immunol Commun. 1981;10(3):251-64.
3. Heimburg-Molinaro J, Lum M, Vijay G, Jain M, Almogren A, Rittenhouse-Olson K.Cancer vaccines and carbohydrate epitopes.Vaccine. 2011 Oct 1.

Gotta love having an email address that ends in ‘.edu’!

Datapunk Logo.

However there were problems with the data files, beyond the fact that they were incredibly huge. They are not in a typically common data file format, where each record is delineated by a carriage return (‘enter’) and each field in the record is delineated by a  tab, comma or pipe (|)  character. The OMIM gene records as weird blend of individual lines that contain data and other lines that name fields, all of which are variable in length and appearance.  I’ve dealt with files like these  before (some KEGG files have this format)  and you have to really work hard to code a way for Perl (the computer language I typically use)  to tease out what you need. Fortunately, Perl has a vibrant community of programmers that produce different ‘modules’ that expand Perl’s capabilities. Thus you do not have to reinvent the wheel if someone has already done it.

One module I use a lot is called BIO::PERL. This has lots of cool interfaces and tools, including one that parses (reads) OMIM gene files. Normally that would be end of the story. However that BIO::PERL module, while doing a good job, was too slow, so I developed a work-around that involved using the module to tease out specific data, which was then re-organized and written to new data files indexed by the OMIM gene ID number. By the time I was done, I have four different data files which the program could quickly query and execute rapidly.

One problem I encountered doing this was the exceedingly complex nature of the data returned from the BIO::PERL parser. Much of it was nested inside a series of ‘hash arrays.’ In the computer world an array is a place to store data, much like an egg carton stores eggs: once the eggs are in the carton, you can specify which egg you want by naming the column and row number of the egg you want. Easy enough, but in computer world, in addition to an egg (or an empty space), the location of any place in our egg carton can also contain the location of another egg carton!

This is how data often gains meaning from organization.

However, eugenics had a far seedier side. For example, in July 1933 Germany passed a law allowing for the involuntary sterilization of “hereditary and incurable drunkards, sexual criminals, lunatics, and those from an incurable disease which would be passed on to their offspring.” Sweden, the USA, Canada, and virtually every non-Catholic country had Eugenic Societies. In the USA, immigration policies were motivated by the goals of eugenics, in particular a desire to exclude “inferior” races from the national gene pool.

As the human legacy of Nazism became known to the postwar scientific community, and it shuddered at its consequences, and many scientists began to look upon genetics and anthropology as the very opposite of race-definers; they saw it instead as a way of showing just how bankrupt the notion of racial stereotyping was.

William Boyd and Isaac Asimov put the first modern scientific approach to race forward in a simple, readable, and completely forgotten book called Races and People. Written in 1955, it is an unabashed championing of the essential value of any human being. Asimov, well known to three generations of Science Fiction readers, had grown up Jewish in an era when significant portions of the world found anti-Semitism innocuous or even virtuous. Boyd, blood type anthropologist, science fiction writer and the discoverer of of the blood type specificity of certain  lectins (talk about a life!), used research with blood groups to demonstrate that the superficial characteristics which so many of us use to define race and determine our value vis-à-vis other human beings are utterly without scientific basis. (1)

Publishing their book in a time when racial segregation and colonialism were still the norm and in the wake of terrible genocide, Boyd and Asimov set the pattern for all future anthropologic and genetic analysis of race. However, with the onset of those classic liberal values we so identify with the 1960’s and 1970’s and their effects in popular culture and academia, the pendulum began to swing the other way round. In scientific circles, race became a non-entity, possessing no significance whatsoever.

'Around a flowering tree, one finds many insects.' - Proverb from Guinea

Boyd defined later race as “not an individual, not a single genotype, but a group of individuals more or less from the same geographical area (a population), usually with a number of identical genes, but in which many different types may occur.” For Boyd, as with Livingstone, you got your racial characteristics from where you live more than from your genes, and this explained why the variability made the notions of race untenable. (2)

Rather than being racists themselves, I think we should consider the early blood group researchers rare beacons of tolerance in a world still coming to grips with the notion of equality for all.

However, just because you say something doesn’t exist doesn’t necessarily make it go away, and it is childish to think that we can contribute to the elimination of racism by putting our heads in the sand with the belief that there are no clearly defined races. One of the primary blood type/ anthropology sources I’ve cited, Frank Livingstone, (3) even rejected the concept of race altogether. Livingstone suggested that the variability in the frequency of any gene does not utilize the concept of race. He pointed out that although it is true that there is biological variability between the populations of organisms which comprise a species, this variability does not conform to the discrete packages we call ‘races’. In other words, there are no races, the are only clines (a ‘cline’ is a gradient of physiological change in a group of related organisms usually along a line of environmental transition). This is still the guiding principle in contemporary anthropology; at least in name, if not in practice. Instead of racial distributions, we now have “clines”: distribution lines very much like those you would see on a weather map. Not surprisingly, most of these clines do a very nice job of delineating population differences that any person could have arrived at by simply traveling to that area and having a look around.

Alice Brues, a well-known physical anthropologist, addressed the folly of avoiding race as a physical characteristic:

“A popular political statement now is, “There is no such thing as race.” I wonder what people think when they hear this. They would have to suppose that the speaker, if he were dropped by parachute into downtown Nairobi, would be unable to tell, by looking around him, whether he was in Nairobi or Stockholm. This could only damage his credibility. The visible differences between different populations of the world tell everyone that there is something there.”

An important paper written against the use of race as a method of classification argued that since the probability of mis-classifying an individual based on variation in a single gene is approximately 30%, race is an invalid taxonomic construct: In short because humans share 50% of their DNA with a rose bush, we must be 50% the same. This was countered by an argument (“Lewontin’s Fallacy“) that argued if one took into account more genetic markers, the possibility of a racial mis-classification rapidly dropped to almost 0%. The counterargument to this counterargument is that if we looked at enough genes we could presumably distinguish Swedes and Norwegians as two distinct races.

Let’s take a moment to remember while that Boyd and Asimov did not deny the existence of race, they demolished the notion of using race to determine an individual’s value. For our purposes, we’ll use race and ethnicity simply to get additional information that may be valuable in helping to design a more intelligent lifestyle for you, the reader. Let’s just assume that you can and do belong to certain human groupings whose members have more in common with each other than they do with other groupings.

What we call a “race” is really just another fact. Moreover, when we try to subsume it into non-existence, we do injustice to both sides of the distinction. When you share a fact with someone, it makes no one the better or worse, just better informed.

‘History is bunk,” wrote the industrialist Henry Ford. It is a quote with the ring of truth in it. We are destined to interpret past events through the eyes of who left the record (usually the winner) and our own modern day thoughts and rationales. Losers rarely write history, and it is just about impossible for the average person to put himself or herself in the mindset of a person living in a world without light, heat, supermarkets, and the Internet.

Science is fact-based, but scientists can sometimes be charmingly naïve. One of the most common ways they display this naiveté is the coining of politically correct euphemisms. Thus, instead of the negatively charged term “race” you sometimes see the phrase “mutually inbred ancestral groups” which, at least to me, sounds even worse.

Despite the gloss, we at least now have a framework to allow us to collect and categorize those genes and polymorphisms that show different frequencies between races.

Called Ancestry-Informative Markers (AIM) this category of genes includes blood groups, markers of pigmentation and other SNP’s that distinguish between races but don’t always result in some visually detectable difference. A collection of AIM’s that distinguish African and European populations contains over 3000 highly differentiated SNP’s.

An example of an AIM gene is called “Duffy,” which codes for the Duffy blood group, The Duffy blood group has a variant that codes for a Duffy blood type (Duffy Null allele) that is found 100% of Sub-Saharan Africans, but occurs very infrequently in other races. Interestingly, like some of the hemoglobins, this variant has been known to provide some resistance to malaria infection.

Another interesting variant of the APOA1 gene (the TT genotype) is seen in high concentration in African Americans. This variant may help to explain their higher rates of heart disease as a genetic factor leading to difficulty in adapting to new nutritional environments.  (1)

Once, after a public lecture, I was approached by an attendee who asked if I was aware that there were criticisms of my work as ‘racist’ on the internet, and that I had derived my conclusions from long-discredited research done by the Nazis in concentration camps. It turned out that the accuser was a zealous follower of veganism , who thought this might be an effective way to quell further interest in my conclusions.

In all of my trolling through the scientific literature on blood groups since 1910 I’ve not recovered a single reference on ABO blood group that supported any of the racial notions then in vogue in Nazi Germany. My suspicion is that if any research was done the results were not supportive of their racist prejudices — i.e. the subjects were more alike on a blood group basis than they would have liked to admit.

1. Boyd WC and Asimov I. Races and People. Abelard-Schuman 1955
2. Boyd WC. 1952 The Contribution of Genetics to Anbthyropology. in Anthropology Today, ed. by A.L. Kroeber,
3. Livingstone FB. 1962 On the non-existence of human race. Current Anthropology 3 (3):279-281.
4. Lutucuta S, Ballantyne CM, Elghannam H, Gotto AM Jr, Marian AJ. Novel polymorphisms in promoter region of ATP-binding cassette transporter gene and plasma lipids, severity, progression, and regression of coronary atherosclerosis and response to therapy. Circ Res. May 11; 88(9):969-73. (2001)