Joseph E. Pizzorno, ND of was kind enough to send along a review of my textbook Fundamentals of Generative Medicine that will appear in the upcoming issue of Integrative Medicine, A Clinician’s Journal.

Most are probably aware of Peter D’Adamo, ND, MIHFI as the author who popularized the blood type diet. Some have dismissed his work as simplistic—typically after only reading his consumer books. Those digging more deeply will find a fascinating, surprisingly well-documented world. However, this book is not specifically about the blood-type diet. Rather, it is the most profound exploration of biochemical individuality ever written. Roger Williams, PhD pioneering work in the 1970s (see the biography I wrote for the very first issue of IMCJ) inspired many of us who later became leaders in this new medicine.

We all believe that each patient is unique. However—and this is one of my pet peeves—too often I see this assertion used as an excuse for the same patient receiving vastly divergent—even contradictory—interventions for the same problem from different integrative medicine clinicians. I think much of this is caused by undisciplined and uninformed clinical thinking due to a superficial understanding of the true uniqueness of our patients. I realize this is harsh, but I think we can all do so much better for our patients. A major reason for this problem is that we have lacked the tools and a road map to truly understand the uniqueness of each patient and how our interventions interact with this uniqueness. There have been no textbooks—until now.

And this is why I am so excited by Peter’s work.

This textbook is published in a loose-leaf format and titled Volume 1. It is a daunting work, written for the healthcare professional seriously committed to deeply understanding their patients. Each of the 6 sections is devoted to a specific conceptual area—not organized by body systems as seen in other medical textbooks. The first section deals with the complexities of biological systems and how chaos and other theories can explain how a system can be dynamic, yet stable. In fact, how a dynamic system is much better able to maintain itself in a changing and challenging environment. The depths of Peter’s scholarly inquiry can be seen in his discussion of Darwin versus Lamarck and how the erroneously dismissed Lamarckism is now seen as the discovery of epigenetics.

The next section is a pretty conventional description of genetics and mutations. Unusual here is his discussion of haplogroups—i.e., the mapping of ancestral migration patterns. Section III continues the discussion of genetics, covering the polymorphisms that now start manifesting in the enzyme variations that produce the biochemical individuality. Again, all pretty conventional.

Section IV is where Peter starts really stretching our understanding by putting what we have learned in Sections II and IV into “morphogenic” patterns. Particularly interesting, and clinically extremely relevant, is phenotypic plasticity and how this holds great promise for “regenerative treatment.”

Section V delves deeply into epigenetics. Fascinating reading, but also scary as the story of how environmental toxins like bisphenol A (BPA) modulate gene expression emerges. Finally in Section VI we get the tools to consciously manipulate gene expression. Peter thoroughly documents how to use specific food constituents, botanicals isolated natural (and synthetic) compounds. As I am writing this on Halloween, all I can say is “Beware the Lectins!”

Strengths: 800 pages and thousands of references documenting biochemical individuality. Will fundamentally change how you think about patients.

Weaknesses: This book will eat all your spare time. It is not an easy read and you will rarely be able to use this as a resource while seeing a patient. Which brings up my major suggestion to Peter—please, we mere mortals need a Cliff Notes version for our office. Even better, how about some logic flow charts like IMCJ contributor Herb Joiner-Bey, ND created for the Handbook of Natural Medicine?

Bottom Line: Buy this book. Read a few pages every night. Your “incurable” patients will be deeply grateful and you will be once again mesmerized by the miracle of life.

Drum Hill Publishing, Wilton CT, 2010. $200.00
* MIFHI = Masters of the Institute for Human Individuality.

What can I say? It is always a sublime moment when a mentor and role-model approves of your work.

As far as practical employment, indeed this is not that book. Volume 2 will be the actual treatise on algorithms. That was the gist of my recent diatribe at the AANP (American Association of Naturopathic Physicians) conference in Portland: a call for a new ontology for this emerging field with the appropriate informatics, heuristics and pattern languages.

Fundamentals of Generative Medicine

I read the most interesting thing the other day. In his wonderful book Wetware Dennis Bray describes how researchers knocked out the gene for brain creatine kinase in mice. They were prepared for severe phenotypic changes and probable death of the animals. Surprisingly, nothing happened. They looked absolutely normal, although a few had slightly smaller brains. Now, how could knocking such an important enzyme produce virtually no change in phenotype? Working by cell network, they discovered that when a primordial system of singular importance is compromised, developmental influences legislate that other gene/enzyme systems simply compensate. It is coded into the system. Perhaps no better proof of this is the ‘small world’ network observation that any molecule in a cell is separated from any other molecule by an average of only three reactions.

So, what can we conclude? Our ‘typical’ clinical realities (linear, reductionist), obey what a mathematician might call ‘differential linear equations’. We start with a map someone previously figured out for us and walk through the forest following it. In biological reality, this is usually seen in higher level hierarchies, typically organelles, symptoms, etc.) Most gene/environment/phenotype manifestations are what I would consider to be ‘von Neumann type non-linear equations’ i.e you take one step towards the forest and with each subsequent step the trees rearrange themselves.

The proof of this is the notion in complexity circles of ‘phase transition’. Stewart Kauffman thinks that life itself lies on the brink of a gaseous/liquid state (for analogy- really we are talking about information here). ‘Liquid states’ in biological systems are characterized by flexible, oscillating (percolation) characteristics, ‘gaseous states’ by non-linear behavior (non-Boltzmann entropy, or maybe what Schroedinger called ‘negentropy’, but to me, more likely, a non-matter/energy ‘Shannon information entropy’ (surprisal versus uncertainty, etc.).

At its most basic, we can knock out CPK and have a rat live probably for the same reason that we can scratch a CD and still have it play.

So, anyway, I’d really like to write that second book, but I know I’m not ready yet.

Tags: biochemical individuality | generative medicine | joseph pizzorno | peter d'adamo | systems biology | wetware

Harvard University has developed an animation that would take their cellular biology students on a journey through the microscopic world of a cell, illustrating mechanisms that allow a white blood cell to sense its surroundings and respond to an external stimulus. What is especially nice is the degree of detail devoted to membrane dynamics and glycosylation mechanisms.

It’s a bit dense and rapid-fire for non-biologists, but play it a few times. There is much to learn here. The motorproteins seem uncannily ‘alive’.

Probably the only thing I don’t like is the cheesy, new-age sounding music. I could think of any number of better soundtracks.

Thanks to Ken Carlin for giving me the heads-up about this gem.

Tags: cell biology | computer animation | glycobiology | motorproteins | protein translation

A

gain and again in my investigations I come up against the greatness of one single man. William Clouser Boyd (1903-1983) appears to be one of those fascinating people who go on to dominate an entire area of research for a generation. It seems as if his creativity knew no bounds. In the 1940’s Boyd noticed that the protein agglutinin in lima bean would agglutinate red cells of human blood group A but not those of O or B. He had in fact discovered that many of these blood agglutinins were actually specific to one blood group or another. With Elizabeth Shapely he coined their modern-day name, lectins, which is Latin for “to pick or choose.”

Boyd was one of the first to begin using blood groups as an anthropological tool. In the years after the First World War, and in the tradition of the Hirschfelds, Boyd compiled the abundant blood group data coming from transfusion centers throughout the world. With his wife Lyle, during the 1930’s, Boyd made a worldwide survey of the distribution of blood groups. On this basis, he divided the world population into 13 geographically distinct races with different blood group genetic profiles. He also studied the blood groups of Egyptian and Amerindian mummies.

By 1950 Boyd had determined about 20 genes for outward appearance traits that are recessive for typical Asians and/or Europeans but homozygous dominant for Africans. These recessive genes include the 6 to 8 genes for light skin color, the genes for blue eyes, gray eyes, blond hair, red hair, thin lips, straight hair, sacral spot, lack of facial hair (beards), narrow nose shape, and some others.

William Clouser Boyd

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 antisemitism innocuous or even virtuous. Boyd used research with blood groups to demonstrate that the superficial characteristics so many of us use to define race and determine our value vis-à-vis other human beings are utterly without scientific basis.

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 1960s and 1970s liberal values we so identify with, 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.

Boyd wrote some excellent science fiction (under the name Boyd Ellanby) including two well-known books, Category Phoenix in 1952 and Chain Reaction in 1956. He also authored Fundamentals of Immunology (1943) one of the first immunology textbooks for medical students.

The night before the IFHI conferences begin it is customary to have a closed dinner for the teaching staff. The 2007 Conference featured the well-known glycobiologist and lectin scientist Gerhard Uhlenbruck. My wife Martha had arranged a special gift for the speakers: by scouring Ebay she had managed for secure several first edition copies of Boyd’s Fundamentals.

When Gerhard opened up his gift I first thought he was going to faint. But then I watched him proceed to lovingly rub the spine of the book, in a manner much like one would greet an old friend. Turns out he has lent his copy to a colleague many years prior and it had never been returned.

Tags: isaac asimov | lectins | paleoserology | william boyd

T

he gene-centered view of evolution (aka gene selection theory or selfish gene theory) holds that natural selection acts through the differential survival of competing genes, increasing the frequency of those alleles whose phenotypic effects successfully promote their own propagation. According to this theory, adaptations are the phenotypic result through which genes achieve their propagation.

The genetic “selfishness” here means maximizing its own transmission, not any other more emotionally or morally loaded meaning of the word selfishness. However the real manifesto of the gene-centered view of evolution is the somewhat self-deprecatory Central Dogma as advanced by Francis Crick (1916–2004), one of the discoverers of the molecular structure of DNA in 1958:

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that information cannot be transferred back from protein to either protein or nucleic acid.

In other words, once information gets into protein, it can’t flow back to nucleic acid. This extreme view of genetic determinism has largely fallen by the wayside. Information jumps all around the genome, from genes to proteins to transcription factors and back to genes. In addition, the information contains in the DNA code is of rather low information density (you can specific any one nucleotide with as little as two ‘bits’ of information: 01, 11, 10, 00). Glycomic influences (attaching branching sugars to proteins) add immeasurably more information density and control much of the actual fate of the proteins coded by DNA.

Prior to Dawkins, the selfish gene concept was advanced by George C. Williams (1926-2010) in his 1966 work Adaptation and Natural Selection. In it, Williams argued that each phenotype is the unique product of the interaction between genome and environment. It does not matter how fit and fertile a phenotype is, it will eventually be destroyed and will never be duplicated.

The natural selection of phenotypes cannot in itself produce cumulative change, because phenotypes are extremely temporary manifestations.

In essence, the selfish gene concept attempts to address the very basic problem whose identification goes back to August Weismann (1834-1914) —what are the levels at which natural selection works? In particular, how and why would natural selection further a trait that is good for the survival of a group or society, but injurious to the individual? An example is the alarm notes sounded by certain species of birds. Although good for the group, a single bird that sounds the alarm risks being identified and perhaps eaten by a predator. According to natural selection, these “altruistic” traits must have been selected because they benefit the group’s survival.

However, there are obvious shortcomings with this argument. For example, if a gene crops up that results in a bird becoming a “non-caller,” one might expect that this gene would spread in the population and replace the genes for altruistic behavior compared with the altruistic “callers” who would become less likely to survive and reproduce.

It's mine!

R.A. Fisher (1890-1962) and J.B.S Haldane (1892-1964) recognized this problem, but William D. Hamilton (1936-2000) provided an answer, in what became known as Hamilton’s Rule. In each behavior-evoking situation, the individual assesses his neighbors’ fitness against his own according to the coefficients of relationship appropriate to the situation. In other words, the beneficiaries of altruistic actions are almost always the members of the altruist’s family. Even if the altruist himself has less offspring, the genes underlying the altruist’s behavior increase in frequency.

The selfish gene concept has been codified (at least for the general public) in the work of Richard Dawkins, particularly in the appropriately titled The Selfish Gene (1976). Dawkins took up Hamilton’s approach and extended it to a “gene’s eye view.” According to Dawkins this selfish behavior can help us to understand the evolution of all adaptive traits. To Dawkins, the genes are “selfish” because they do not concern themselves with the reproductive success of the individual insomuch as they are interested in the propagation of the gene in subsequent generations.

To Dawkins, we are the “survival machines” of our genes. Key to the concept of the selfish gene is the belief that the inheritance of acquired characters, or even phenotype in general, are not an evolutionary factor in any real physical sense. Genes are not naked in the world. They are usually packed together inside a genome, which is itself contained inside an organism. Sort of like microscopic interstellar travelers, genes build vehicles to promote their mutual interests of jumping into the next generation of vehicles.

Dawkin’s theories have had their opponents, including the evolutionary biologist Ernst Mayr (1904-2005):

Yet the funny thing is, that if you ask a man in the street who the greatest living Darwinian is, he will say Richard Dawkins. And indeed, Dawkins has done a marvelous job of popularizing Darwinism. But Dawkins’ basic theory of the gene being the object of evolution is totally non-Darwinian.

From Charles Darwin’s 1876 letter to Moritz Wagner:

In my opinion, the greatest error which I have committed, has not been allowing sufficient weight to the direct action of the environment, i.e. food, climate, etc., independently of natural selection.

Stephen Jay Gould (1941-2002) took issue with the gene as the unit of selection, arguing that genes are not directly “visible” to natural selection. Rather, the unit of selection is the phenotype, not the genotype, because it is phenotypes that interact with the environment at the natural selection interface. To Gould, gene differences do not cause evolutionary changes in populations; they register those changes.

Dawkins and his critics were united in assuming that genes are the only unit of heredity relevant to the evolution of organisms, and that acquired traits are not inherited, so it would be hard to consider the criticisms of the selfish gene concept as anything other than disagreements inside of an admittedly genocentric camp. Regarding the inheritance of behavior, the selfish gene hypothesis comes up rather short, a fact that Dawkins has himself acknowledged, promoting the idea of selfish genes instead as a “thought experiment” and as a “powerful and illuminating metaphor.”

Idea as Gene

One concept in The Selfish Gene I’ve always liked was Dawkins’ notion of a meme. For those who have never heard of the concept, at its simplest, a meme (rhymes with dream) is an idea. Any idea. It is simply something that gets stuck in the human mind.

Examples of memes are tunes, ideas, catch-phrases, clothes fashions, ways of making pots or of building arches. Just as genes propagate themselves in the gene pool by leaping from body to body via sperms or eggs, so memes propagate themselves in the meme pool by leaping from brain to brain via a process which, in the broad sense, can be called imitation. If a scientist hears, or reads about, a good idea, he passed it on to his colleagues and students. He mentions it in his articles and his lectures. If the idea catches on, it can be said to propagate itself, spreading from brain to brain.

The 'Apple Underdog Meme' positions its competitors as dictatorial Big Brothers.

You can think of a meme as a sort of ‘thought replicator’ stored in our human brains and passed on by the imitation of others. Some memes are helpful, others can be harmful. For example if you pulled up to a man on the side of the road that looked like a policemen, you might expect directions to a particular location to be accurate. However, people can simply walk into a uniform store and buy a policeman’s uniform. Some people may see a connection with memes to brain washing or thought manipulation, but that would not the case in anything but a tiny fraction. Most memes are passed along as a desire to inform, assist, or make a special statement about ourselves.

Our minds are not a blank slate on which any idea can be impressed. To be understood, a new meme must connect to the values and process that are already available to the individual. In addition one must also be willing to believe it or to take it serious. For example, although you are likely to understand the proposition that cartoon animals can talk with each other, you are unlikely to accept the proposition that this occurs in the real world without very strong evidence. Therefore, you will not add it to your ‘information base’ on animal characteristics. The cartoon meme will not manage to change your view on the subject.

Some writers think there are two basic types of memes: procedural and propagative. A good meme, like a good virus, will have special characteristics that insure continued growth. Without them, they eventually die.

• Fidelity: The ability to maintain accuracy and correct errors to maintain integrity.
• Fecundity: The fertility of the idea. The ease by which an idea it spawns itself. To me, this appears to be environmentally dependent. ‘Cultural relevance’ is probably a critical aspect of meme fecundity.
• Longevity: The longevity of an idea is related to how relevant it continues to be, as its meme is passed to newcomers and future generations.
• Co-adaption: Effective memes tend to thrive in the company of other replicators that compliment them.

Cancer as a Selfish Gene

What the selfish gene hypothesis does accomplish is provide an underpinning for the disturbing notion that genetic determinism can sometimes work at bewildering cross-purposes. The genes in an organism sometimes “disagree” over what should happen. That is, they appear to have opposing effects. For example, in some mammals, a gene in males may want to produce lots of healthy sperm, but others may want half the sperm to be defective. Some genes in a female may want her to nourish all her embryos; others might want her to abort half of them. Some genes in a fetus may want it to grow fast, others slowly, and yet at an intermediate rate. Some genes want to protect chromosomes from damage. Others want to damage it.

These conflicts arise because genes can spread into a population despite sometimes being harmful to the larger organism. These genes might give themselves a benefit but typically cause problems for other non-linked genes in the same creature. In that sense, they are indeed selfish. In fact we can define selfish genes by just such intent: stretches of DNA (genes, fragments, non-coding DNA, portions of chromosomes, whole chromosomes) that act narrowly to advance their own interests (replication) at the expense of the larger organism. This in turn leads to selection of other genes that try to suppress this activity, and thereby mitigate the harm. This evolution of selfish genetic elements and their relative control attempts inevitably leads to “intragenomic conflict.”

Most selfish genetic elements contrive to be transmitted as a disproportionate percentage into the organism’s progeny. Instead of being our idyllic, Mendelian 50%, selfish genes might manage to get into 66%, 99% or 50.01% of the organism’s progeny. Genes inherited in a biased manner can spread into a population without doing any good at all for the organism; it might even be harmful. Such a gene is said to “drive” or be “driven.”

Cancer is the ultimate intragenomic conflict, a selfish cell lineage. It is the inevitable results of the fact that cells within a multicellular organism are not quite genetically identical to each other, and become even less like each other over time, an effect that is inevitable, and is strongest in long-lived ones. Humans are genetic mosaics and within our bodies cell lineages can expand or contract according to their tendency to proliferate.

Cancers have evolved high rates of replication, compared with other cell clones, at the expense of host fitness. Precisely because cancers are harmful to the organism, there will be selection for properties of adaptations that can prevent or delay their occurrence. An indication of the importance of these adaptations can be seen when comparing adaptations in our own species to that of mice. Of the wild mice in the laboratory, raised under benign conditions, 46% will have gross tumors at death. Humans are 3000 times larger and live 20-30 times longer than mice, so if the probability of a cell becoming cancerous was the same per unit time in us as in mice, none of us would make it out of the womb alive, let alone reach puberty.

Portions excerpted from Fundamentals of Generative Medicine copyright 2010, Drum Hill Publishing, USA.

Tags: cancer | central dogma | darwin | dawkins | meme | memetics | natural selection | selfish gene

I

recently put a picture of myself (circa mid-70’s) on my Facebook page. It generated quite a few comments, but by far the most interesting came from Kristin, a long-time web friend, who asked “what words of wisdom could I give to that young man in the photo?” I replied that my advice would be –that if he were around long enough– he’ll probably have to live with all his choices, but not necessarily all his circumstances.

A decidedly deterministic take on things I’ll admit, but still, a rather useful heuristic that apparently does find its place in more life processes then you’d think.

The Game of Life, or simply Life, was invented in the early 1970’s by the mathematician John Horton Conway. Life is a zero-player game, meaning that its evolution is determined by the initial state of the cells and thus requiring no further input. Executed on a grid of squares (cells), each in one of a finite number of states (much like the ancient game of Go) you interact with Life solely by creating an initial configuration and then simply observing how it evolves —typically through some sort of computer algorithm. Like real life, Life evolves through iteration, and iteration requires the dimension of time.

In the Life grid of squares a “cell” can be live or dead. Putting a marker on its square shows a “live cell.” A “dead cell” is simply an empty square. Each cell in the grid has a neighborhood consisting of the eight cells in every direction including diagonals. Life’s evolution is determined by its initial state, requiring no further input from humans. One interacts with Life by creating an initial configuration, turning it on, and observing how it evolves.

Life has some very simple rules, which are repeatedly run with each iteration of the game:

• A empty cell with exactly three live neighbors gives birth to a new cell.
• A live cell with two or three live neighbors survives and stays alive.
• In all other cases a cell dies or remains dead (from either “overcrowding” or “loneliness”).

• The number of live neighbors is always based on the cells before the rule was applied. In other words, we must first find all of the cells that change before changing any of them.

Rules for Conway's 'Life'

Despite its simplicity, Life achieves an impressive diversity of behavior, fluctuating between apparent randomness and order. One of the most interesting features of Life is the frequent occurrence of “gliders” (arrangements of cells that essentially move themselves across the grid) and other high order-clusters of organization.

Life is just one example of a cellular automaton, any system in which rules are applied to cells and their neighbors in a regular grid. It is one of the simplest cellular automata to have been studied, but many others have also been invented, often to simulate systems in the real world. Life is the study of how elaborate patterns and behaviors can emerge from very simple rules. It helps us understand, for example, how the petals on a rose or the stripes on a zebra can arise from a tissue of living cells growing together. From a theoretical point of view, Life is interesting because it dynamically has the power of computation: Conway was able to show that Life in certain circumstances could model a “universal Turing machine,” essentially a very basic computer.

Possibly because it was viewed as a largely recreational topic, little follow-up work was done outside of investigating the particularities of Life and a few related rules.

Life is a intricate web of many simple components acting in complex ways.

Conway’s Life is one of the simplest examples of what is sometimes called emergent complexity or self-organizing systems.

The complexity of an object or system is a relative property. A fundamental feature of complex systems is that they consist of many (or at least several) integral parts that are connected via their interactions. Their components are both distinct and connected, both autonomous and to some degree mutually dependent. It is more or less universally accepted is that complexity is situated in the time-space between order and disorder.

Fifty years ago, if a group of scientists were asked to define the key to life, the great majority would point to metabolism; how we obtain energy from food. However, adding all the required molecular components and stirring it up will not produce an organism. A more modern view of molecular biology is concerned with organization in time and space. How do the molecules of life arrange themselves throughout the cell’s compartments, how do they move around, and communicate so as to synchronize their actions? We can ask this question because we can now inspect the working cell at a molecular level and take snapshots of its molecules doing their business. And it is a community of daunting complexity.

There’s no sense in being precise when you don’t even know what you’re talking about.

—John von Neumann

Tags: cellular automata | game of life | game theory

J

ean-Baptiste Pierre Antoine de Monet, Chevalier de Lamarck (1744 – 1829) was a French naturalist and an early proponent of the idea that evolution occurred and proceeded in accordance with natural laws. Lamarck is however remembered today mainly in connection with a discredited theory of heredity, the inheritance of acquired traits (“Lamarckism”) He was also one of the first to use the term “biology” in its modern sense.

The Chevalier.

After serving in the army, Lamarck became interested in natural history and writing a multi-volume flora of France. After years spent working on plants and believing that species were essentially unchanging he began to investigate invertebrates (another term he coined). Working with mollusks he grew convinced that transmutation or change in the nature of a species did occur over time and set out to develop an explanation, which he outlined in his 1809 work, Philosophie Zoologique. In this work he encapsulated his theories into two “laws”:

• In every animal that has not passed the limit of its development, a more frequent and continuous use of any organ gradually strengthens, develops and enlarges that organ, and gives it a power proportional to the length of time it has been so used; while the permanent disuse of any organ imperceptibly weakens and deteriorates it, and progressively diminishes its functional capacity, until it finally disappears.
• All the acquisitions or losses wrought by nature on individuals, through the influence of the environment through the influence of the predominant use or permanent disuse of any organ are preserved by reproduction to the new.

Lamarck saw spontaneous generation as ongoing, with the simple organisms thus created being transmuted over time and becoming more complex and closer to some notional idea of perfection.

Like Hans Driesch’s work a century later, Lamarck believed in a teleological (goal-oriented) process where organisms became more perfect as they evolved. Teleological explorations try to interpret the purpose, or “end reason” behind things. It is most often contrasted with metaphysical naturalism or physicalism, the position that everything that exists is no more significant than the sum total of its physical properties.

Most modern geneticists reject most teleological implications by nature, although as the geneticist J.B.S Haldane (1892-1964) observed:

Teleology is like a mistress to a biologist: he cannot live without her but he’s unwilling to be seen with her in public.

Lamarck’s defenders believe he is unfairly vilified today. They note that he believed in organic evolution at a time when there was no theoretical framework to explain evolution. He also argued that function precedes form, an issue of some contention among evolutionary theorists at the time.

Darwin not only praised Lamarck in the third edition of The Origin of Species for supporting the concept of evolution and bringing it to the attention of others, but also accepted the idea of use and disuse, and developed his theory of pangenesis partially to explain its apparent occurrence. Like many of his contemporaries Darwin believed in the inheritance of acquired characteristics simply because before the discovery of the cellular mechanisms for genetic transmission the idea was the most plausible.

Nowadays, the idea of passing on to offspring characteristics that were acquired during an organism’s lifetime is called Lamarckism. Lamarckism would go on to a long life in thousands of high school biology classes, serving as an example of “what not to do.” This view was, until very recently, thought to be inconsistent with modern genetics, certainly until the discovery of epigenetic (post-genomic) inheritance.

Tags: lamarck | lamarckism

T

he summer of 1968 beckoned and looked very promising. I had just successfully navigated the 5th grade and could anticipate balmy days spent butterfly collecting, trading comic books, listening to baseball on the radio, and playing afternoon stick-ball, a uniquely New York City street game involving a stick –usually appropriated from an unwatched broom– and a hard pink rubber ball manufactured by the AJ Spaulding Company universally referred to as a “Spalldeen.”

Stick-ball.

However my dreams for such a bucolic near future came to a screeching halt one afternoon when I was greeted by my little brother at the door with news that we would all soon be flying in an airplane! That sounded exciting enough, but further elaboration disclosed a darker truth: We would be flying to the village of my mother’s birth in North East Spain. My knowledge of the place was minimal at best: I had only seen rather quaint photographs with scallop-cut edges of what appeared to be a ramshackle, sleepy and sun baked town populated by sunburned farmers with dazzling white teeth clustering around a new tractor, scooter or calf. It looked foreign, smelly and somewhat ominous.

Soon enough we headed for the airport to begin our journey. Modern, security-frazzled, airline customers may not realize or remember just how much of an event traveling by airplane was in the mid 1960’s. Washed and scrubbed, wearing rayon shirts and thin ties, mother in Sunday best complete with pill box hat, we journeyed the Atlantic in the marvelous Boeing 707.

Fully jet-lagged we landed many hours later at Barcelona airport and were greeting by a deputation from the village, 150 screaming, waving and wildly gesticulating Catalans, for this was, as I would soon be told “Catalonia, not Spain.” From Barcelona we soon began our travels westward, into the Llobregat river valley and the mountains of the Montserrat, strangely carved peaks that are the results of eons of erosion by now-extinct giant rivers. This is an enchanted land; not for nothing are Catalan artists overrepresented in the Surrealist art movement.

Winding down roads of choking dust, we made our way to the town, or pueblo. Until then having grown up in the restrained, plasticized and sanitized habits that characterized the USA in the 1960’s, I was in no way prepared for the coarse, almost brusque mannerisms of these folks. The gesticulated wildly, seemed to argue about everything, screamed at each other from their windows and talked at an amazingly rapid-fire rate of delivery. It’s phenomenally fertile land, and the local people are rumored to be the only people in Spain who can “make bread out of stones.” The closest town, which is at the border between Catalonia and Aragon, was described as being “renowned for its figs, and the thick-headedness of the inhabitants.”

Culture shock soon set in. A shy kid to start off, I was soon just happy to find a quiet place and read my bon voyage present, a fortunately huge book on the battle of Gettysburg. Unlike my little brother, who was muy sympatico, eating in the café and yelling at the soccer games on the one TV like everyone else, I just felt alienated. One had to be careful with their choice of friends. The headless automaton jumping around my aunt’s kitchen spurting blood all over the place was just shortly before the chicken with two different colored eyes that I had so carefully observed that morning. Cute, friendly rabbits were soon rendered into grotesque hanging parodies of the “visible body” model that I had built that Christmas.

Being the wonderful people that they are, my family soon began to try to get me to come out of my shell. One of my uncles took notice of my liking of history, and soon we were off in his tiny car, visiting Visigoth and Roman ruins. Another uncle, a simple but lovable farmer, would take me out to his fields, hold a finger up to his lips so as to say “let’s keep this secret to ourselves” and begin pushing aside sagebrush, rubble and other weeds, revealing a lovely Roman husband and wife gravestone. Gradually, I began to open up to this wonderfully simple and pure world.

Around midday we would break for lunch and siesta, which never varied all that much; a medium sized fish, called a “sardine”, stuck on a branch and placed around perimeter of a small fire, some olives and almonds from the field, followed by a peach or pear. Since it was still too hot to go back to work we’d look at clouds or the distant hills and at one point I asked him what lay beyond those hills.

“Saragossa.” He said.

“And beyond that?”

“Navarre.”

“And beyond that?”

“The Basques. But they are different than us, and a little crazy.”

It would take a lot for a Catalan to call someone else “different”, and to a Catalan, the Basques may well be the only qualifying group. Like the Catalans, the Basques are very independent minded, with great cultural sensitivity and were consequently heavily repressed during the Franco dictatorship. Similarly, they have experienced a phenomenal cultural renaissance in the years following his death.

An ancient people, or more correctly a “people island,” they have resisted virtually all attempts at assimilation, forced or otherwise. In the Basque language there is no name for “Basque”. There is a name for the language that Basques speak, Euskera and a Basque is simply defined as a Euskaldun, someone who speaks Euskera.

But we would have to go back farther still to get a grip on the Basques. You have to go back to a very cold, dry time without agriculture. The Basques, you see, are sort of living fossils, probably the most direct link we genetically possess to a distinct people that can be traced back to the Pleistocene Age.

The upper right-hand corner of Spain has some of the most interesting dialects to be found in the world over such a small piece of geography. Catalan, the language of my family, is an ancient Latin derived tongue, probably closer to the Latin of the Romans than either modern day French or Spanish.

For a romance language, Catalan has a surprising number of consonants, with the free use of the letter x as an example. But for all its unique qualities, Catalan is a relative newcomer, the Romans having inhabited the area roughly two-thousand years ago. Prior to that the population was a hybridization of two earlier groups, rather short, dark haired and eyed indigenous people, called Iberians and taller, lighter transplanted Celts who arrived a few hundred years prior to the Romans in search (like their modern-day counterparts) of a warmer climate. These two groups intermingled freely, fused and produced what historians called the “Celt-Iberians.”

Yet these modern languages are distinct from Basque Euskera or any of the Semitic or African languages as well. English with it clipped and nasally sounds; German with its guttural mega words; French, with its mellifluous hints of romance and Hindi, with its beautiful Sanskrit writing all share Indo-European as a common ancestor.

In the early 1600’s Pierre De Lancre, a French witch hunter, speculated why the Basque area seemed to harbor so many witches. He thought the problem stemmed from their great numbers in the various Jesuit missionaries, with all their evangelizing, which had affected them with demons from far-off places that they had carried back to Spain. De Lancre also thought that their early adoption of tobacco use might also be working on their minds. He held Basque women in special contempt, saying that they produced only undersized and cursed children who died.

The Genetics of the Basques

As Mark Kurlansky recounts in The Basque History Of The World, this last accusation may have had a ring of truth to it, since Basques are renowned among anthropologists for their strikingly high percentage of individuals who have the Rhesus negative (RH-) blood group genotype (dd): 60% compared to an average of 16% for the rest of Europe. When a mother is Rh- and she gives birth to Rh+ children, an immune reaction can occur which gives rise to a hemolytic (“blood destroying”) anemia, and often would lead to the death of the child.

The word haplotype is a combination (portmanteau) of the phrase “haploid genotype.” A haplotype is the genetic constitution of an individual chromosome. A genotype is distinct from a haplotype because an individual’s genotype may not uniquely define that individual’s haplotype. The haplotypes in the human genome have been produced by the molecular mechanisms of sexual reproduction and by the history of our species.

We humans are diploid (have a pair of each type of chromosome, so that the basic chromosome number is doubled. Our haplotype will contain one member of the pair of alleles for each site. A haplotype can refer to only one locus or to an entire genome. A genome-wide haplotype would comprise half of a diploid genome, including one allele from each allelic gene pair.

A.E Mourant suggested that modern day Basques have other characteristics, which may mark them as descendants of the late Paleolithic population of Western Europe: They share a skeletal resemblance to Cro-Magnon man and they are the only Western European people who do not speak a Indo-European language.

Unlike knuckle hair, where we could conceive of a single allele being dominant to the other, with Rhesus (Rh) blood groups it’s the relationship of two gene chunks, each composed of three independent alleles. The Rhesus system has more than 40 antigens, is the most complex blood grouping system of them all. The most significant antigen is D, followed by C, E, c, and e antigens. Ronald Fisher, in partnership with Robert Russell Race developed one of the two nomenclatures called the Fisher-Race Theory, used for describing the genetics of the Rhesus blood grouping system, the other being the Rh-Hr Nomenclature of Alexander Weiner.

The difference between the two systems is pretty straightforward: In the Fisher-Race System each gene controls of the product of the corresponding antigen. In other words the D gene produces D antigen, c gene produces c antigen etc. However, the d gene was hypothetical, not actual. We all inherit a set of three Rhesus (Rh) genes from each parent as part of a haplotype.

A haplotype is a chunk of alleles at different places along the same chromosome that are inherited as a unit. Sort of like if you went to a clothing store, bought a blue sweater, and wound up being convinced by a very good salesperson that the sweater would look great with this pair of plaid pants.

To finish the story of the Rhesus blood group, if the maternal genome was Rh haplotype cDe and the paternal genome cde haplotype, the offspring would be Rh positive. Actually any capital letter will make you positive, but a capital D is especially positive, which is why Rh status is often simply a matter of “big D” or “little D.” The Basques are interesting when it comes to Rhesus blood group: 50% are cde/cde, the highest percentage of Rh- blood group in the world.

Thus De Lancre’s observation that Basque women produced only undersized and cursed children who died may have had a ring of truth to it.

The hemochromatosis gene (HFE) has a polymorphic variant (c282y) that is found in very low incidence among the Basques, who instead have the H63 variant. The c282y variant is sometimes called the Celtic polymorphism because it is found in a very large percentage of Celtic people.

It has been speculated that the c282y variant may have been an adaptation to decreased dietary iron in cereal grain-based Neolithic diets. Both homozygous and heterozygous carriers of the HFE c282y mutation have increased iron stores and therefore possessed an adaptive advantage under Neolithic conditions. An allele age estimate places the origin of the c282y mutation in the early Neolithic period in Northern Europe and is thus consistent with this hypothesis. c282y seems to be the result of an effort to “accumulate” the non-heme iron found in plants as a response to the lowered intake of animal products occurring with the conversion of hunter-gathering to neolithic agricultural practices.

The Basques are culturally and geno-graphically unique, thought to be a mesolithic remnant settling in the northern area of Spain before the LCM (Last Glacial Maximum). The high frequency of type O Rh- blood and the low incidence of the c282y polymorphism may indicate that these three genes relate to preferences for heme (animal-derived) iron.