Henry Ford, it is said, commissioned a survey of the car scrap yards of America to find out if there were parts of the Model T Ford which never failed. His inspectors came back with reports of almost every kind of breakdown: axles, brakes, pistons -- all were liable to go wrong. But they drew attention to one notable exception, the kingpins of the scrapped cars invariably had years of life left in them. With ruthless logic Ford concluded that the kingpins on the Model T were too good for their job and ordered that in future they should be made to an inferior specification.

For the automotively challenged, the kingpin is the main pivot in the steering mechanism of a car or other vehicle. Originally this was literally a steel pin on which the moveable, steerable wheel was mounted to the suspension. It is usually made out of metal.

This story, well-known on the internet, was originally told by Nicholas Humphrey in 1976, and often referred to by other biologists including Jared Diamond and Richard Dawkins, the latter recounting the story in what is, by far, the most pessimistic chapter ("God's Utility Function") in his book River Out of Eden.

John Hawks, who has an interesting anthropology weblog takes a look at the Henry Ford story, and why evolutionary biologists seem to love it so:

Of course, the truth is natural selection doesn't cut back the quality of functional parts easily, either. Selection also has to overcome fixed costs in order to change populations: costs stemming from pleiotropy, epistasis, and coevolution with other kinds of organisms (e.g. predator-prey relationships, mutualisms, and mimicry). How much selective advantage can come from reducing femur diameter a smidgeon? It can't be very much, and it might easily be outweighed by the manifold costs of changing osteoblast function to accomplish it. In other words, adaptation is constrained by the same sorts of problems that constrain industry. Ruthless efficiency can rarely be maintained in biology or in manufacturing.

But then again, was the story even true?

Barbara Mikkelson over at the Urban Legends website thinks not, but offers an additional insight:

Though the legend is almost always positioned as a "let's screw the consumers" tale, on rare occasion it has been presented as an example of intelligent design."*

It all reminds me of the Edward de Bono books I read as a kid.

* She includes a similar type of anecdote about another engineering triumph, from WWII:

"A proposal was made to armour bombers in the places where the returning planes showed most damage from anti-aircraft fire. One young analyst suggested that instead, the planes should be armoured where the returning bombers showed no damage. He inferred that the planes that did not return were being damaged in the places that the returning planes were not. His suggestion was implemented and an X% reduction in lost planes resulted."

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. So, 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 SNPs that distinguish between races but don’t always result in some visually detectable difference. A collection of AIMs that distinguish African and European populations contains over 3000 highly differentiated SNPs. An example of an AIM gene is called “Duffy” and it codes for the Duffy blood group. A variant codes for a Duffy blood group 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.

Looks like it’s time for another one of my semi-autobiographical digressions.

By the mid 1970’s I had completed the required college level classes to allow my application to a college of naturopathic medicine, since by then I had determined to follow in the footsteps of my father and enter this (at the time) obscure and curious profession. This was a time of great difficulties for this tiny healing art; more naturopaths were retiring and dying than entering the schools, and the future of the profession indeed looked rather bleak. There were tiny glimpses of hope however at least in the one remaining school, where the “Old Guard”--most often gentlemen who had learned their trade in the 1920’s and 30’s—- were giving way to “Young Turks”; aging hippies and other political rejects from the 1960’s. Unfortunately this was not at all harmonious, and at the time I was to apply we heard that the school was in uproar, as one faction or another had locked it opposite out, changed the locks, kidnapped the files –you name it.

So instead, we looked across the Atlantic, to The British College of Naturopathy and Osteopathy, and upon acceptance, I duly relocated to the “Post-Swinging London” of the late 1970’s, which as it turned out was in a rather downtrodden phase, with escalating energy prices, joblessness and at times civil unrest. This was the era of the “Urban Punk” and “Anarchy in the UK”. One only had to look around to see heart-wrenching tableaus of its more hypocritical aspects: Homeless folks sleeping against under banners proclaiming the Queen’s Silver Jubilee.

Jobs were scarce, and as a foreign student, it would have been virtually impossible to get the few that were available. I had a small stipend, and made a “few quid” doing some odd jobs. Nonetheless the dire economic circumstances forced a series of relocations, each typically one level further down the social level than the one prior. Yet these were happy times, with great friendships and new experiences, more so when I landed at the charming London neighborhood of East Finchley, a quiet suburban backwater about five miles from London City Center.

Again, as long before, a pleasant and affluent suburb, East Finchley in 1977 was the infrastructure and architectural equivalent of a visit to an eccentric, wealthy, emphysemic great-aunt. While sipping tea and hearing of the “old days” you might gaze upon the fine wood details of the hand made furniture or the anonymous faces in the dulled and dusty photographs on the wall, often in the poses of stern solidity or in an exuberant moment of victory. It would seem that only the passage of time could dull the greatness of all that past glory.

If Great Britain was at its mercantile and military zenith by the beginning of the 20th century, even more so was its pre-eminence in the rapidly growing fields of genetics, statistics and evolutionary biology. In 1890, at the pinnacle of the gilded greatness that was Victorian England, doughty old East Finchley witnessed the birth of one the greatest of her sons, a man who in the words of a one historian was a “genius who almost single-handedly created the foundations for modern statistical science.” His name was Ronald Aylmer Fisher.

The son of a successful businessman, Fisher was had a precocious intellect, and because of his poor eyesight learned mathematics without the use of paper and pen; leading to a marvelous ability to visualize problems in geometrical terms, and to forever frustrating both teachers and students by being able to produce mathematical results without setting down the intermediate steps.

Fisher published an important paper in 1918 in which he used powerful statistical tools to reconcile what had been apparent inconsistencies between Charles Darwin's ideas of natural selection and the recently rediscovered experiments of the Gregor Mendel. Among many and varied later accomplishments, it was this singular achievement that gave birth to modern evolutionary science. This was completed with the publication of The Genetical Theory of Natural Selection in 1930.

In 1943 Fisher accepted the Chair of Genetics at Cambridge University. Photographs invariably show a bearded, white haired, bespectacled man, with very thick glasses owing to his extreme myopia. More often that not, a billowing pipe accompanies the picture. He was addicted to the crossword puzzles of the London Times, which in characteristic fashion he filled in only those letters where the words crossed each other. His eccentricities, termed by his student “Fisherania,” though sometimes embarrassing, where more often the source of great entertainment to his friends.

Johann Wolfgang von Goethe wrote that “Certain flaws are necessary for the whole. It would seem strange if old friends lacked certain quirks.” Certainly Fisher had his flaws. He was an early and enthusiastic proponent of Eugenics, a social theory advocating the improvement of human hereditary traits through various forms of intervention, including sterilization, prenatal testing and screening, genetic counseling, birth control. Fisher was also opposed to the developing argument that smoking caused lung cancer, partially due to his dislike and mistrust of Puritanism and perhaps also due to the solace he had always found in his pipe.

Although he would rapidly wash his hands of the more dunderheaded students, Fisher was a inspirational mentor to his acolytes, many of who would go on to stellar careers of their own in the field of genetics, statistics and anthropology. These ranks included the previously mentioned A.E Mourant, who did work with Fisher on the epidemiology of Rh blood group genetics; Robert Race and Ruth Sanger (who my friend Gerhard Uhlenbruck once described as 'Being married-- but to other people.') themselves later on co-authored an acclaimed textbook on blood groups; A.W.F. Edwards and Luca Cavalli-Sforza, who studied the “relatedness” among various population groups.

The British biologist Conrad Hal Waddington conceived of genotype (your genetic plan) passing through environment into phenotype (the physical you) as a walk through an 'Epigenetic Landscape'. He conceived a mode of visualizing this process, in which phenotype development is seen as marbles rolling downhill. In the beginning development is plastic, and a cell can become many fates. However, as development proceeds, certain decisions cannot be reversed. This Landscape has hills, valleys, and basins and marbles compete for the grooves on the slope, and eventually coming to rest at the lowest points, which represent the eventual types of tissues they become.

The Epigenetic Landscape. (After Waddington, C. H., 1956, Principles of Embryology)

Waddington was a big thinker. Not only did he visualize development as passing through the peaks, slopes and valleys of the Epigenetic Landscape, he considered this process one of increasing constraint, or as being "canalized� as he referred to it: That the early choices influence the later options. If we think of the canals of Venice, the analogy works even better; our little gondola floats from one canal into another and then another. Each choice leaves it fewer options than before, and since gondolas need water, so we can't just pick it up and put plunk it into another canal.

Now just for a moment visualize a newly fertilized egg. It already contains all the wisdom and information needed to eventually go on to produce a completely formed human being in its DNA, but over time it must develop various cell lines (called germ layers) that can then go off and further distinguish themselves as arteries, nerves and organs. Its unfolding is stochastic (a process that is non-deterministic in the sense that the current state state does not fully determine its next state.).

"Stochastic" is one of those great words that is more often misunderstood than understood. It is often quoted as being synonymous with random, but the actual Greek seems to imply something closer to "unknowable." It's often used in the arts (very often in music composition.)

In short: We know it's going to happen; we just don't know what is going to happen.

Your journey from genetic imprinting (the genes that were determined at conception) to full phenotype (the physical you) is to a great degree a stochastic process. which is why Waddington's metaphor is so great. Any architect will tell you that a house almost never winds up like that original plans. Environmental variables (cost of materials, availability) alter reality as the construction project moves from one stage to the other. We cannot always predict the eventual outcome, but we can describe and learn about the landscape in which it takes place and that, to a degree allows us to understand things.

Hindsight is always 20/20, because the outcome almost always describes the process.

That journey started long before your conception, since epigenetic gene control is hereditable.

You are in essence, not what you eat, but rather what your parents, grand parents and even great grandparents ate. Unlike defective genes, which are damaged for life, epigenetically controlled genes can be repaired. And, activation and silencing tags that are knocked off can be regained via nutrients, drugs, and enriching experiences. (1)

Conceivably the cancer you may get today may have been caused by your grandmother's exposure to an industrial poison 50 years ago, even though your grandmother's genes were not changed by the exposure… or the mercury you're eating today in fish may not harm you directly, but may harm your grandchildren (2)

These inherited traits can continue to influence the onset of diseases like diabetes, obesity, mental illness and heart disease, from generation to generation.

All in all, the next few years should prove most interesting...

The post-genomic era, which is fueled by automation and other technologies, provokes a change in our grossly naive view of genetic determinism (that single genes govern complex traits) to the obvious reality that most human diseases are complex entities. Gene(s), although necessary, contribute only partially to disease, while environmental factors, lifestyles, epigenetics and epistasis significantly influence pathophysiology and, eventually, the expression of transient biomarkers that can be utilized for diagnosis and prognosis. Human osteoarthritis and rheumatoid arthritis are multifactorial, complex diseases. The genetic inheritance of these diseases remains elusive, although they tend to run in families wherein some siblings have a two- to tenfold increased risk of developing the diseases.

From: Future of genomics in diagnosis of human arthritis: the hype, hope and metamorphosis for tomorrow
Ashok R Amin?, Seth D Thompson? & Shailey A Amin
Future Rheumatology
August 2007, Vol. 2, No. 4, Pages 385-389

Epigenetic alterations have been known to be of importance in cancer for ~2 decades. This has made it possible to decipher epigenetic codes and machinery and has led to the development of a new generation of drugs now in clinical trials. Although less conspicuous, epigenetic alterations have also been progressively shown to be relevant to common diseases such as atherosclerosis and type 2 diabetes. Imprinted genes, with their key roles in controlling feto-placental nutrient supply and demand and their epigenetic lability in response to nutrients, may play an important role in adaptation/evolution. The combination of these various lines of research on epigenetic programming processes has highlighted new possibilities for the prevention and treatment of metabolic syndrome.

From: Nutritional Epigenomics of Metabolic Syndrome
Catherine Gallou-Kabani, and Claudine Junien
Diabetes 54:1899-1906, 2005

Full Article

1. Asim K. Duttaroy Evolution, Epigenetics, and Maternal Nutrition 2006 Darwin Day Celebration.

2. Montague T. A New Way to Inherit Environmental Harm. Synthesis/Regeneration 39 (Winter 2006)

This Transfusion: Sword swallowers and sore throats | ABO in Neanderthals| Blood groups and endometriosis | Nutrigenomics and personalized diets | This News This Week

Welcome to The Weekly Transfusion, 1.6 for the week of April 26, 2009.

Sore throats more common in sword swallowers

Sword swallowers run a higher risk of injury when they are distracted or adding embellishments to their performance, but injured performers have a better prognosis than patients who suffer iatrogenic perforation....Major gastrointestinal bleeding sometimes occurs, and occasional chest pains tend to be treated without medical advice. Sword swallowers without healthcare coverage expose themselves to financial as well as physical risk.

Article Link

Comment:

I guess it is just that old 'occupational hazard' story, sort of like the study that discovered that woodpeckers don't seem to get headaches.

Genetic characterization of the ABO blood group in Neanderthals

The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans. We have analysed two male Neandertals that were retrieved under controlled conditions at the El Sidron site in Asturias (Spain) and that appeared to be almost free of modern human DNA contamination. We find a human specific diagnostic deletion for blood group O (O01 haplotype) in both Neandertal individuals. These results suggest that the genetic change responsible for the O blood group in humans predates the human and Neandertal divergence. A potential selective event associated with the emergence of the O allele may have therefore occurred after humans separated from their common ancestor with chimpanzees and before the human-Neandertal population divergence.

Article Link

Comment:

Certainly one of the major evolutionary advantages of being blood type O was their double-barreled antibodies; this blood type being the only one that reacts to both “A things” and “B things” in the environment. This probably provided an extra layer of protection against any number of epidemic diseases (plague, smallpox) and many endemic ones (flukes and parasites) as well. If this immune “hyper-vigilance” would go on to increase the rates of inflammation and auto-immune disease in their modern descendants, it should also be remembered that these are often diseases of later life, typically past child bearing and rearing age. Thus if it were a late-model alteration, it certainly provided a significant survival advantage. The Founder Effect can be seen in the characteristics and distribution of the genes for Rhesus Negative and O blood type among the early Mesolithic Period during the so called- ‘Happy Paleo’ period, which also shows some correlation with the ancestral haplogroups R1b and I. On the other hand blood type A seems to have conveyed a better chance of surviving the ‘lean’ period of the early Neolithic; a slightly different, perhaps better way to starve. Type A’s more tolerant immune system may have given them the benefit when it came widening the diet and exploring new foods.

ABO and Rh blood groups distribution in patients with endometriosis.

The blood group A was more predominant in women with endometriosis, while blood group O was less predominant. The overall risk of women with endometriosis and A blood group was 2.89 (95%CI, 1.85-4.52). No significant difference was detected in ABO and Rh blood groups in women with endometriosis according to the severity of disease. CONCLUSION: Women with endometriosis have a 2.9-fold increased risk in the A blood group distribution. The role of blood groups in the development of endometriosis remains to be determined.

Article Link

Comment:
I verified the observation back in 1988, when we were observing whether increases in opposing blood group antibodies were associated with any reproductive illnesses. We observed that in our small endometriosis group, all women were type A, and all virtually had elevated antibodies to foreign blood types (in their case, blood type B ). It did seem at he time to be an area ripe for future research, but I never got back to it. It is nice to see that others have observed the same tendencies.

The antibodies in the ABO system (isoagglutinins) called anti-A and anti-B are not normally present at birth. The antibodies develop between 3-6 months of age due to the stimulation of the newborn’s immune system by microbes and foods that possess antigens of an opposing blood type. In, for example, type O children, they will begin forming to type A and B red cell antigens as soon as the child starts eating food, because the A and B antigens are actually found in quite a number of plants. So, as soon as the child starts eating plant food, she'll be exposed to those antigens and start making antibodies against them.

Nutrigenomics and Personalized Diet: From Molecule to Intervention and Nutri-ethics

The relationships between food, nutrition science, and health outcomes have been intensively analyzed over the past century. Genomic variation among individuals and populations is a new factor that enriches and challenges our understanding of these complex relationships. Hence, the rapidly emerging intersection of nutritional science and genomics - nutrigenomics - was the focus of a special issue of OMICS: A Journal of Integrative Biology in December 2008 (Part 1). The OMICS Nutrigenomics Special Issue (Part 2) February 2009 is The relationships between food, nutrition science, and health outcomes have been intensively analyzed over the past century. Genomic variation among individuals and populations is a new factor that enriches and challenges our understanding of these complex relationships. Hence, the rapidly emerging intersection of nutritional science and genomics - nutrigenomics - was the focus of a special issue of OMICS: A Journal of Integrative Biology in December 2008 (Part 1). The OMICS Nutrigenomics Special Issue (Part 2) February 2009 is now available free online

Article Link

Comment:
Two entire issues on personalized nutrition with virtually no mention of any of the bio-markers that really determine individualized dietary functionality: ABO blood groups and secretor status. Maybe these bio-markers are just too low-tech for the average scientist. More likely, the nay-sayers behind the smear campaign I've had to endure over the last ten years have had their desired effects.

No matter, if you read enough history you soon realize that Billy Shakespeare had it right: 'Truth will out.'

News of the Week

• April 28 2009: Dr. Peter D'Adamo - Lecture at Backus Hospitalthe basics of 'Eating Right For Your Type.' Open to the general public. More information
• June 5-7 2009: Personalized Medicine in Form and Function. A weekend intensive seminar with naturopathic physician, scientist and author, Dr. Peter J. D'Adamo in Norwalk, CT. This seminar provides training in personalized nutrition determination using blood grouping, secretor status, epigenetic indicators, dermatoglyphics and biometrics. Extensive overview of the latest clinical and laboratory techniques, information systems and pharmacology. Certification will also be offered. Presented by the Institute for Human Individuality. CME's may be available. More information. SEATING IS EXTREMELY LIMITED. RESERVE YOUR SEATS NOW!

Until next time.

In addition to my feverish efforts to bring www.dadamo.com back into the Information Age ---the shoemaker's kids do in fact often lack shoes--- the so-called holiday week finds your humble blogger finally mastering the intricacies of Apple's wonderful Keynote presentation software. If like me you've always used PowerPoint, Keynote is indeed a revelation.

The purpose of using presentation software is to give presentations and my upcoming lectures in Arizona are providing the necessary threat-impetus.

At the request of the Arizona Naturopathic Medical Association (AzNMA) on Saturday, January 10, 2009 I'll be doing a total of four hours of lecturing to docs and a one hour public lecture (with a half hour reserved for questions and answers) at the Doubletree Paradise Valley in Scottsdale, AZ. If you are in the Phoenix area why not plan to stop by. I can promise you that the slide/multimedia/rumination presentation may well give old Al Gore a run for the money.

Any trip to Phoenix also affords the extra benefit of seeing our good friends Paul and Laura Mittman. I'm so proud of what Paul has accomplished at Southwest College.

Found this little unused snippet from the volumes of material that was prepared for The GenoType Diet but never used. Thought it might make for interesting reading.

The high water mark of hunter-gathering is often called the Mesolithic period ('Middle Stone Age') which began around 10,000 years ago and ended with the introduction of farming. The onset of farming differed from place to place, starting early in the Near East and much later in Europe. Hunter-gatherer technology reached its apex during the Mesolithic era; fishing tackle, stone adzes, canoes and bows have all been found preserved at various sites.

Popular culture tends to depict our Stone Age ancestors as crude, simplistic animals perpetually at the point of starvation. "Solitary, poor, nasty, brutish and short" as Thomas Hobbes had put it in 1651. Nothing could be farther from the truth. Though small in number, Paleolithic hunter-gatherers worked far fewer hours and enjoyed more leisure than typical members of industrial society, and they still ate well, satisfied with very little in the material sense. The transition from hunting and gathering to agriculture was not necessarily a one way process, and evidence seems to disprove any notion that hunter-gatherers were saved from extinction by the advent of farming technology. They seem to have been familiar with farming practices when it arose, but for the longest time simply rejected it, or used it as a marginal supplement to the diet.

As these late hunter-gatherer societies evolved, they began to develop specializations such as fishing and seafood collection, harvesting nuts and fruits, or trapping small animals. They often had simple forms of representative government, based around family or clan.

Perhaps it is not coincidental that the story of the Garden of Eden in the Bible shares some of the same elements in its storyline. Some anthropologists have hypothesized that the Garden of Eden does not represent a geographical place, but rather represents cultural memory of the simpler times of hunter-gathering, when man lived off God's bounty, as opposed to being civilized and toiling at agriculture.

A large percentage of the world's cultures have stories of a Great Flood that devastated earlier civilization. This flood is sent by God or the gods as an act of divine retribution to destroy civilization. Noah and the Ark in Genesis, Matsya in the Hindu Puranas and the Epic of Gilgamesh are among the most familiar versions of these myths, all of which divide prehistory into a pre-flood or Antediluvian and a post-flood world.

Certainly there were major changes to the planetary water table at the end of the last ice age, as melting waters for the rapidly diminishing glaciers would have caused the levels of the seas and oceans to rise about 125-150 feet, deluging and destroying many prior land bridges, such as that between Alaska and Siberia, and isolating many populations. The end of the last ice age was also accompanied by the mother of all volcanic eruptions as the movement of the African plate opened a fault-line under the Mediterranean Sea, creating a string of volcanoes that still exist, such as Vesuvius and Etna. There is some geological evidence suggesting that a massive prehistoric flood occurred around 8000 years ago as the Mediterranean Sea spilled into the present day Black Sea.

William Ryan and Walter Pitman, geologists from Columbia University proposed what came be called the 'Black Sea Deluge Theory' which hypothesizes that melting of the last great glaciers caused the rising Mediterranean to finally spill over a rocky sill at the Bosporus eventually flooding 155,000 square kilometers of land. Despite some supportive findings, the theory remains an active subject of debate among archaeologists.

Although by this time agriculture had already reached the plains of central Europe, the Ryan and Pitman linked its spread with farming people displaced by the flood. It has been suggested that the memories of these displaced survivors was the source of the Great Flood Legends.