Dr. Peter D'Adamo: Personalized Healing

Growing up in Brooklyn I remember many exciting and fun filled trips to Manhattan --or as anyone from Brooklyn calls it, “The City.” One of the features I always looked forward to seeing was a huge advertisement for a paint company that featured a can of paint pouring itself over a globe of the world, its byline proclaiming “We Cover the Earth with Our Paints.”

Excepting the obvious question as to why anyone would ever want to cover the world in it, paint is not a bad metaphor for how most scientists viewed inheritance before Mendel, it being a sort of “blended essence” --a mix of the features of both mom and dad, much like how we might combine white and black paints to make gray. In the late 1800s Charles Darwin proposed a mechanism of inheritance by means of gemmules, imaginary granules or atoms which are continually being thrown off from every cell or unit, and circulate freely throughout the system. Yet Mendel’s research showed that it was nothing of the sort; being in fact much more digital, like how a computer makes all sorts of interesting stuff out of what are essentially zeros and ones. Mendel’s theory nixed that notion completely, although after a while things started to be observed that appeared to indicate that genetics wasn’t all that black and white, on and off after all, but I’ll save that for a later story.

I’ve married a blue eyed woman, and have two daughters. The first daughter has brown eyes just like me. Simple enough: My brown-eyed alleles squash my wife's blue-eyed ones. However, my second daughter has greenish-hazel eyes, much lighter than mine or her sister, but certainly not bright blue like those of my wife, so it would seem like a little blending is going on over there after all. Eye color is not a simple dominant-recessive trait, although knuckle hair and tongue rolling are. The eye color trait is what geneticists call polygenic, which simply means that it is not decided by one single gene. In order to account for my younger child’s green-hazel eyes, we have to add other factors to the mix.

My wife is pure Irish on her mother’s side and a mix of Slovakian and Hungarian on her father’s. Hungarians have the highest percentage of green eyes of any population, close to 20%, so something in my wife’s blue-eyed world (the blue-eyed allele of her Hungarian father) produced a variant that refused to role over and die, but instead made alliances with other genes --including a recently discovered one that may go back to the Neanderthals--- that slips green eyes and red hair in between things, ultimately producing my younger daughter’s wonderful green eyes. Given that, you'd think I'd get the tongue rolling gene and she the knuckle hair, but alas, the results are quite opposite.

Many traits are polygenic, and when when added to the tremendously under-appreciated epigenetic effects on gene expression, explain why we have never found a single gene for diabetes, or cancer or Alzheimer’s disease. If it were that simple, we’d have had the answers to these questions already.

Another type of inheritance is very close to my heart. The allele (the set of alternate genes for any trait) for type O blood is recessive to the alleles for type B and type A. Again using my family as an example, biologically I am type A blood and my wife is type O. My daughters are both type A blood, so we know that they must have received a type O allele from mom and a type A allele from me. Their genotype for ABO blood type is A/o (recessive alleles are usually depicted in lower case, dominant in capitals, and genetic things are usually rendered in italics).

If I was instead type B blood and had provided a type B allele, the children would have type B, as type B is dominant to type O as well.

But here is where things get interesting. What happens if you were to receive one type A allele and one type B allele? Why, you would be blood type AB! The reason behind this is that although both B and A clobber O, they strike a tentative truce between themselves and split the kingdom and declare a dual monarchy. This is called co-dominance. There are not many instances of co-dominance in genetics, and ABO inheritance is almost always given as the example.

You may well ask why, if type O is recessive to types A and B, why hasn’t it disappeared, leaving only A and B to slug it out, and eventually producing a world of only type AB people? The reasons and proofs for this are mathematical, so I won’t bore you with them, but suffice it to say that if a population is large enough, and the individuals in that population tend to mate randomly, and there are no other major influences (such as one type being more resistant to an infectious disease), after one generation the gene pool will stabilize and reach a sort of equilibrium.

Since there is such a huge amount of o allele in the human population (so much so, in fact, that even though it is the recessive allele, individuals with type O blood constitute the majority of most populations around the world) it will keep propagating itself, whereas the type you’d have though would be replacing everyone else by now, AB, comprises at best about 2% of the population.

Most people probably have a negative concept of mutation, spawned by a slew of admittedly great science fiction. However, it might surprise you to learn that that vast majority of mutations, at least the ones that get incorporated into our genetic heritage, are not lethal and often don’t do very much at all. For example, let’s again turn to our trusty blood types. As we will explore in more later on in this book, genes are chunks of DNA that do things, like code for specific proteins. Although DNA is an incredibly long molecule (if all the DNA in all your cells was unwound and placed end to end it would produce a string capable of reaching to the sun and back several times) it is composed of a simple string of four repeating nucleotides abbreviated A,T,C and G. The sequence of these four repeating nucleotides is what contains the instructions for the protein.

The difference between having the gene for type A blood or type B blood is a variation of a mere seven letters out of the total of 1,062 that make up the entire gene. We even know exactly where they differ: letters number 523, 700, 793 and 800. If you are type A blood, you have C,G,C,G in these locations, whereas if you are type B blood you have G,A,A,C there instead. Yet however slight this difference is, it is enough to cause a major problem if you were to receive the wrong blood in a transfusion. These are called point mutations because they are a simple one-letter misspelling in a gene, unless as in the case of blood type it is a consistent variation that is inheritable, in which case it is called a polymorphism.

The type O gene mutation is even more interesting. It derives from a frame shift mutation. If you are type O you may be surprised to discover that rather than having a difference of letters, like A and B, you're just missing one letter, number 258, entirely.

So hopefully by now you are comfortable with the notion that mutations are just part of life, unless of course you are unfortunate enough to have gotten a lethal one (and there are many) which probably would never have allowed you to get so far in life as to be able to read this blog. Many, if not most, of these mutations are spontaneously terminated while the sufferer is still an embryo in utero. Virtually all of the well-known genetic disorders are semi-lethal.

There are may causes of mutations, including viruses and radiation, but the most common cause is the simple fact that when our cells reproduce, they must make a complete copy of there DNA, and sometimes the copies don’t turn out so great. Think about the photocopy of that great joke that circulated around the office cubicle the other day. If it was barely legible, with bloated letters that ran one into the other, it was probably because someone made a photocopy of the original, which was quite likely a photocopy of the previous copy. Each time a copy was made of a copy, the writing was degraded a bit more.

Genes are like that. Often as we get older, we tend to get more and more of this “photocopy effect”. Perhaps what was once a word string of CAG became CAA. Even if it is copied correctly, it will be CAA from there on. Perhaps not unexpectedly these mutations are called “copying errors” and given the enormous amount of cell division that goes on over the course of a lifetime it is the real surprise is just how good of a job we do at it.

Fascinating presidential election; certainly a very unique and historic outcome. It will be interesting to see --given the perilous state of affairs we find ourselves in-- whether 2008 is also the first presidential election in which (come January) it is the winner rather than the loser who demands a recount.

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.

Although just about everyone knows something about DNA, I’d like to take a few moments to introduce you to RNA, the real power behind the throne.

Protein represents what biologists call phenotype – the living, breathing, metabolizing part of life. DNA is information. Other than acting as a blueprint and occasionally remembering to replicate itself, it doesn’t have a single real world obligation. It is RNA that acts as the bridge between DNA and protein, translating the message of DNA into the reality of proteins. All the basic functions of the cell require RNA. Copies of the desired DNA gene message are first copied onto one type of RNA, which is then read by a machine composed in part by some more RNA to create proteins by linking amino acids which are delivered by another type of RNA.

Let’s start the second part of our story with the sweet, if short life of Messenger RNA, or mRNA.

At a certain point in its life, the cell may get an urge to make some sort of protein or enzyme. Let’s say that you have developed an untidy habit, like smoking cigars. As anyone who has ever tried one can tell you, the first experience with nicotine is usually far from pleasant, with dizziness and nausea the usual end result. This reaction occurs because the new smoker has yet to habituate himself to the poisons in the cigar and has not yet developed a way to detoxify and break them down. Over time the continued smoking of cigars sends an environmental message to cells of the liver telling them that they need to make higher levels of the enzymes used to detoxify tobacco toxins. This message (“hey, he’s trying to kill us out there!”) travels to the cell nucleus, where special machinery locates the section along the DNA that contains the gene to produce these detoxifying enzymes, snips it open and unravels that part of the DNA to expose the blueprint.

At that point an enzyme called RNA polymerase comes along, reads the DNA code and makes an RNA copy by linking together similar building blocks (a stretch of RNA is similar to DNA except that RNA is almost always single-stranded and uses the nucleotide Uracil instead of Thymine). This is called “transcription” and just like a court stenographer transcribes the court proceedings, so RNA transcripts the proceeding necessary to make a protein. The RNA strand, called Messenger RNA, (mRNA) is then extensively primped and tweaked to clean it up and get it just right. From here it is about to embark on the ride of its life.

Once everything is set to go, the mRNA is shot through the one of the many pores which act as gates between the cell body and the nucleus. Once out into the cell proper it is carried to the real workhorses of protein synthesis, the ribosomes. Using a railroad analogy, you can think of a ribosome as a dispatcher in the rail yard, whose job it is to assemble an entire freight train. Each time the phone rings the dispatcher gets his next order:

“Fetch the Baltimore and Ohio flatbed with the Honda Hybrids on it. Attach it to the Union Pacific 3985 locomotive.”

“Next, locate and attach the milk tanker from Happy Cow Farms.”

And on and on, until you have one of those interminably long freight trains that take twenty minutes to pass by the railroad crossing as you desperately try to get to the airport.

Just like our rail dispatcher, ribosomes get the information from messenger RNA, by zipping along the code like an old fashioned ticker-tape, reading the code called 'codon triplets' to determine which amino acid to fetch, then linking that amino acid to the prior one, and fetching the next instruction, etc. until it gets a stop message.

In this job the ribosome is assisted by a different type of RNA called Transfer RNA which acts like a crusty old rail yard worker, bringing the appropriate amino acid to the ribosome. At some point the protein is finished up and released, and the messenger RNA decomposes back to the basic building blocks of DNA and RNA, called nucleotides, and ready to do it all over again.

From there the sky is the limit. Proteins are interesting in a lot of ways but perhaps most interesting in their folding tendencies, a molecular origami if you will. Depending on the amino acid sequence and length proteins will fold into a myriad number of complex three dimensional shapes, and it is these shapes that give them their unique powers over the environment.

For example a protein of a certain shape may function as an enzyme, taking sugar molecules and attaching them together, turning single sugars onto cellulose, an important dietary fiber. The protein that results from our string of amino acids might be an insulin molecule, helping to control the owner’s blood sugar, or even a protein that helps DNA do its job, perhaps even part of another ribosome!

As I said, the sky is the limit.

The RNA Queen is so basic to life that many scientists think that perhaps life originated with it, and not with DNA: That DNA came along later as a way to 'memorialize' the work of RNA.

Because I attended a Catholic grammar school which was private and did not receive any state or government funding, we were often dispatched on extenuated and cheerless forays out into the public in a quest for its nickels and dimes. This usually included the sale of various candies or 'chance books,” a cluster of five or ten tickets which entered the owner into a drawing of some sort, for a variety of possible prizes.

Never mind that this same public (due to the limitations of spatial geography and the ambulatory capacities of a ten-year old) was already paying through a myriad of other schemes to keep their kids in this very same school. Typically after suitable introductions had been made and accompanied by sufficient eye-rolling and entreaties heavenward, the wallet would be procured and another book of chances sold. Usually, I’d take the opportunity to remind them of what a wise investment they had made, only to be greeted by the sobriquet “Sonny,” and the dismissal of a future possibilities with an off-hand “I’ve never won anything, and I’m not very lucky.”

From that point to this, I’ve always marveled when people tell me that they aren’t very lucky, since of course it is not true. Just wondering about your unluckiness, marks you as being among the luckiest of all. As a matter of fact, you have won one of the greatest raffle prizes of all time; at odds so astronomical so as to be incalculable. You’ve won the raffle of life.

Just think. Your parents first needed to have come from genealogical lines that survived through all the plagues, wars and accidents of time. Second, they needed to be in physical proximity, so as to come into contact with each other. Third, they had to be attracted in such a manner as to stimulate (hopefully) the urge for procreation in each other. Fourth, they had to be in that particular mood at just the time when the team “up at bat” sperm and egg-wise was you. Fifth, the sperm that carried the genetic information from your father had to compete with millions of other sperm in a race that would make the New York City Marathon look like a trip to the store for a newspaper. Sixth, even upon winning, that sperm had to find an egg at just the exact time when it was ripe for fertilization. Finally, after fertilization, the embryo had to travel through the Fallopian tubes and implant in the uterus where it developed form the cluster of cells into something that would eventually grow to the point where it could take care of itself.

So who among us is unlucky?

In continuing my work on developing The Individualist Wiki, again and again I come up against the greatness of one single man: William Clouser Boyd.

William C. Boyd.

• Boyd wrote the first textbook of immunology.
• Boyd discovered the blood type specificity of many lectins.
• Boyd coined the word 'lectin.'
• He was one of the first 'paleoserologists', using lectins to trace the blood type distributions of many populations around the world. Boyd was the first to document that blood group substances could be recovered intact from physical remains of graves, such as from mummies.
• With Isaac Asimov, he wrote a book for the general public which was one of the first to attack the notion that race was a scientific fact.
• He developed antibody techniques, such as precipitation and flocculation, and applied them to blood group serology.
• He was among the first researchers to recommend the use of magnesium salts in the immediate aftermath of heart attack.
• Boyd wrote some pretty good science fiction (under the name "Boyd Ellanby" ).

Every time I venture into something, be it ABO blood group immunology, lectins in foods, anthropology, and a slew of immunology techniques, this guy was there first. It's a pity nobody really knows about him.

Best serologist, ever.