Dr. Peter D'Adamo: Personalized Healing

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.

You are a collection of cells, literally trillions of them, each with a specific design and function. With a few exceptions, cells have a basic architectural design, most of the time being depicted as looking like a fried egg cooked sunny side up. However, in reality they are three dimensional beings, so it might be better to think of the average cell as a golf ball that you’ve cut across its midline. The “white” of our cell model is the body of the cell, and here are found many specialized areas called organelles that do particular jobs, much like our own internal organs have specific jobs as well. The “yolk” of our cell model is called the nucleus, and in this compartment there lies the object of our affections, the chromosomes.

Chromosomes were first discovered at the end of the 19th century by a German biologist named Walther Flemming. Flemming was looking at cells under a microscope and got the idea to use colors to dye the cell to make it easier to see things. The idea must have worked better than anticipated since he at once began to see spaghetti looking things in the nucleus that dyed a very deep color. As is the fashion, he named these entities chromosomes which is Greek for “colored bodies”.

Chromosomes are one of the more dynamic faces of Nature; they have to be, since they are responsible for the passing on of the Baton of Life that we call reproduction. The number of chromosome in the cell nucleus differs somewhat from species to species. We human have 46 chromosomes; dogs have 78; alligators 32; cabbage plants 18.

Your chromosomes are both the governess and chauffeur of the most important molecules in your body; DNA. Like any blueprint, DNA needs to read in order for the work order to be constructed. Now, DNA is a long, long molecule. If it were completely unraveled it would be about six feet long, yet so thin that it would be invisible. If the entire DNA, in every cell of your body, was stretched out and laid end-to-end in a straight line, it would reach to the sun and back over one thousand times.

I think an effective way of describing the dynamic qualities of the chromosome is to use a few metaphors. My older daughter likes to knit, so we often visit the knitting supply shop in town for fresh yarn. Yarn usually comes wrapped in skeins, a length of yarn wound around a reel. Most yarn comes in lengths of 80-150 yards. One of the nice things about buying yarn this way, rather than just as one long unwound string, is that you can put it under your arm and walk to the car. This is certainly better than tying a knot to the rear bumper and pulled the unwound string all the way home. Thus, the first important lesion of chromosome dynamics; if you’re going to reproduce you’ve got to stuff that entire DNA into a very small, tight package. Chromosomes are just that: tight packages of DNA.

On the other hand, it is very difficult, if not downright impossible to knit anything if the skein of yarn still has the paper label wrapped around it. In order to use the yarn, you have to unwind it. That’s the formula: when the cell needs to use DNA to get information about how to make a protein, it has to unwind it. When it needs to reproduce, or turn off the DNA information flow, it needs to concentrate and condense it.

DNA is packaged and concentrated by special proteins termed histones. This concentrated DNA is called chromatin, which is the DNA plus the histones that package DNA within the cell nucleus. Chromatin structure is also relevant to DNA replication and DNA repair.

Histones are very cool bead-like proteins that spool the DNA in a way that makes it either tighter or looser, sort of like the cardboard around which our skein of yarn is wrapped. Histones respond to changes in their structure by tightening the DNA wrap or loosening it. Whenever a cell needs to access the genetic information encoded in its DNA, the histones on the section of the DNA that is needed undergo a chemical reaction called acetylation by which a molecule called an acetyl group is stuck on the histones, causing them to relax and unravel. When business is concluded for the day, special enzymes come along and chomp off the acetyl group cause the histones to become de-acetylated, which makes them tighten up again, sending the DNA in the region back to its resting state. Think of it like this; when your DNA needs to work its histones chow down on acetyl groups for breakfast and they do yoga; when it needs to reproduce or shut down, the histones lift weights --the strain of which causes the acetyl group to pop out of their mouths.

Only until recent times have we understood this mechanism, and of its supremely paramount importance: That it is used by the environment to influence gene function and that influence, for either good or bad, can be passed on as inheritance. Amazingly, we not only inherit the genes from our parents, but state of histone acetylation of the genes as well. Thus, the histone acetylation patterns of the genome are a prime mechanism of epigenetic inheritance, along with DNA methylation.

Scientists have given each human chromosome a number, according to its size; thus chromosome number 1 is the largest, then number 2, etc. Chromosomes come in pairs, one from each parent. So there are 23 pairs, for a total of 46 in us humans. Numbers 1-22 are non-sex chromosomes called autosomes, and pair 23 contains the X and Y sex chromosomes.

In the few minutes it has taken to read up to here, this, around 400 million of your red blood cells were depleted and replaced, consistent with the set of genetic instructions contained in your DNA. This is where the genetic code comes in.

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.

I wrote this note as a comment on my colleague Rick Kirschner's blog:

Hey Rick,

I thought long and hard on this, especially since I've spent a lot of time dealing with misrepresentations of my own work. On one hand there is the ever-present desire to turn the other cheek and convert my response into a teaching opportunity. This works in certain circumstances --often if the skeptic is actually curious about that which they are skeptical of.

Most are not.

In most other circumstances, turning the other cheek will often get that side of your head smacked as well. As Ho Chi Minh once said in reference to Mahatma Gandhi, "Had he grown up in Vietnam, he'd have ascended into heaven long before he did."

Because these people are often prisoners of their own zealotry their tactics are not very often of the velvet-glove variety. Since they don't respect that which they are skeptical of, and anything goes and every tactic is permissible

Of course this automatically brands them as pseudo-skeptics not skeptics, since true skeptics are more than happy to amend an existing opinion with the presentation of new evidence. Most of these guys just feel that modern allopathic medicine (and hence the public) is under attack from vicious, dangerous woo-merchants and it is their anointed job to exterminate this vermin.

Thus it is unlikely that appeals to reason will ever work effectively, since dialogue is not what they are interested in -- anymore than someone would ever be interested in dialoging with a cockroach before they stepped on it. People who dialogue with cockroaches usually don't step on them.

Like Ho, Adolf Hitler also had an opinion of Gandhi, remarking once to Lloyd George: 'Why doesn't someone just shoot him and be done with it?'

Let's call a spade a spade: The more extreme of these 'anti-SCAM' pseudo-skeptics will not rest until we're completely discredited and eliminated.

Thus their tactics and criticisms are almost always of the 'gotcha' variety. This is usually performed by trying very hard to cover their opponents in manure so that they can stand back, point to them and say 'look, they are covered in manure.'

Gerhard Uhlenbruck, the worlds leading lectin researcher, and one of the few scientists who has openly acknowledged the value of my work has a nice way of reflecting on the silliness of what these people do with their time:

"Never chase a lie. Let it alone, and it will run itself to death."

Stephen Jay Gould also had a nice way of turning the tables on pseudo-skeptics. This from 'The Structure of Evolutionary Thinking' (2002):

"If none of the foregoing charges can bear scrutiny, strategists of personal denigration still hold an old and conventional tactic in reserve: they can proclaim a despised theory both trivial and devoid of content. This charge is so distasteful to any intellectual that one might wonder why detractors don't try such a tactic more often, and right up front at the outset. But I think we can identify a solution: the "triviality caper" tends to backfire and to hoist a critic with his own petard -- for if the idea you hate is so trivial, then why bother to refute it with such intensity? Leave the idea strictly alone and it will surely go away all by itself. Why fulminate against tongue piercing, goldfish swallowing, skateboarding, or any other transient fad with no possible staying power?

So, if Uhlenbruck and Gould are correct, why do so many people spend some much time making life miserable for people with new ideas?

Probably because, although we talk of ideas, it all distills back down to power and money. New ideas often threaten the exact type of person who (personality-wise) would go on to make the perfect pseudo-skeptic. The type of person who buys into the existing power structure, hook, line and sinker. Anything that takes away from the reflected light ('My son the doctor.') they have spent so much time and money on gaining. For which they so sacrificed and assiduously played the game in order to secure. This is not just a threat -- it is also a nightmare.

So what is the answer?

Like any test of will (and for a myriad of reasons) victory goes to those with the ultimate staying power.

In military terminology there is a tactic called 'the refuse.'

Back in the old days, these guys would just line up opposite each other on some level field and go at it. Typically, since most people are right-handed, the right side of an army's line would often be stronger than the left. Thus the idea of any good commander would be to 'refuse' to fight (usually by slowly pulling back) on his left side while trying to press the advantage on his right.

This is a fundamental tactic in Aikido martial art. It is called 'entering,' the idea being to enter inside the physical space of the attacker and then by turning as you enter, you align your force with his and for a brief transcendental moment, see the world as he sees it. Very hard to have a fight with someone who is trying their hardest to see your point of view. It is very hard to hit something which has as its ultimate goal to be where you are not.

I stopped writing for pseudo-critics years ago: You can't please them, they won't buy your books anyway and the people I really want to help educate don't want to read that type of stuff.

I just refused to do it.

Now, while most magazine articles critical of my theories have long-ago been relegated to the landfill, you can still buy my first book only in hardcover despite being twelve years in print.

Why? Because the theory works in many people and they go on to tell other people.

Now, if I need to buy a new hammer I'd be somewhat interested in reviews that tell me which hammers 'not to buy,' but ultimately if my best friend tells my which brand of hammer he's happy with, I'm probably going to go with that advice. I would also find questionable reviewers who had nothing good to say about all hammers in general.

Let's commit to always doing the hard work. Let's accept the fact that we practice a revolutionary form of medicine and let's stop looking for approbation from the very people whose preeminence we threaten and who cannot appreciate the strides we've made and the struggles we've endured in order to put this profession back on its feet.

Let every patient see the value of what we can do. These pseudo-skeptics will always have their coffee claches; their little goldfish bowls, where naturopaths do nothing right and allopaths nothing wrong. But let's refuse to make it into something bigger than it really is, because that is not the main battlefield.

Instead, let's wake up every day determined to redouble our efforts to improve the lives of our patients.

I'll end this diatribe with two more Vietnam Era quotes, which to me seem oddly relevant since US health care is currently in a Vietnam-like quagmire.

The first is from Lyndon Johnson, a fundamentally un-quotable president. Johnson did once say something I thought was of note. In dealing with criticisms of his Great Society program, he was heard to say:

'It takes a master carpenter to build a good barn. Funny thing though, is that any fool with a match can then burn it down.'

Let's remember that we are master carpenters. The public can be trusted to see the benefit of good barns. Let's also refuse to put the matches in the hands of our opponents.

The second quote is from a meeting between a Vietnamese general and an American general in Hanoi several years after the war ended.

'You know' said the American general, 'you never beat us in a single battle.'

'Yes, that is true.' replied the Vietnamese general, 'however it is also irrelevant.'

Remember water always beats rock. That's because water can go around rock. Let's refuse to butt heads with rocks.

And as the quote goes "Medicine progresses funeral by funeral."

They were referring to the doctor's funeral, not the patient's.

Take care and good luck with the new book.

Peter

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?