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.