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Wednesday, March 26, 2008



Dr. Lester CN Simon

When old country folks think you are force-ripe but they really love you and want to see you come good, they will tell you stories like the one about the young village boy who was apprenticed to an old sorcerer. Like all apprentices, the boy longed for the day when he could do all the things his master did, and more. But his miserly chores were confined to fetching water and cleaning the sorcerer’s workshop. One day, the sorcerer departed and left the boy to do his customary, mundane duties. Seizing the opportunity, the apprentice dressed up like the sorcerer, searched through the magic book and enchanted a broomstick to do all the work for him.

However, as the broomstick fetched the water, cleaned and washed the floor, the water was truly more than floor and the workshop became awash with water. Not knowing the magic words to enchant the broomstick to stop, the boy chopped the broomstick into pieces. But each piece continued to fetch more and more water and do less and less mopping. It was truly a disastrous case of mopping and the pipe running. The tail of the tale sees the sorcerer returning and breaking the magic spell.

In the story, the sorcerer returns, but in real life, there is no “Return of the Jedi”; the sorcerer does not come back. How then do we control the natural inquisitiveness of humans and the potentially disastrous waywardness of all societies? For quite some time now but more so recently, economists have been applying economic principles to matters that at first appear to be outside their realm but which, on closer scrutiny, operate on the same basic principles. In fact, the more you study any discipline whatsoever, the more you are drawn to the concept of one universal common sense, a universal logic, a theory of everything.

If economists can apply basic economic principles to many forms of human behaviour, maybe doctors can do the same using basic principles of medicine in general and of pathology in particular and see how they apply to life not just in vitro or in vivo but “in socio’’, or to use the correct Latin phrase, in congregatio.

A gene refers to a strand of DNA. DNA is the abbreviated name for a complex array of different chemical units. Genes are generally knows as traits that we inherit from our parents. DNA contains regions that are called coding sequences and these determine what the genes produce. DNA also contains non-coding sequences. These non-coding regions act to regulate the genes.

Proteins are the products of genes. Their manufacture requires that the DNA (containing the genes) be transcribed into another chemical strand called messenger RNA, which then translates the genetic code into the manufacturing of proteins. This transcription followed by translation arrangement defines the heart of the genetic hierarchical structure, in which the master chemical, DNA, is conserved in the nucleus whilst its properties are transcribed to messenger RNA which then leaves the nucleus and translates the code through the assembling of amino acids into proteins. Is there a biblical parallel here? Ironically, some viruses, like HIV, are RNA viruses and they have the ability to reverse the transcription process and make DNA from RNA.

Whenever we discuss DNA and genes we must remember en passant that a small portion of DNA resides outside the nucleus in a small but critically important structure called mitochondria, whose job is to provide most of the energy we need. A remarkable fact is that whilst we get our nuclear DNA from both parents, all of us, males and females, get our mitochondrial DNA from our mothers only, not from our fathers. This raises legitimate, non-blasphemous questions, unless there was some post-Adam molecular revolution, about the origin of Adam’s maternal mitochondrial DNA.

The Human Genome Project refers to the international collaborative scientific research effort to determine the sequence of human DNA and identify the structures and functions of all the genes it carries. There is still some unfinished business to attend to but a rough draft of the human genome was finished in 2000 and announced jointly by then President Bill Clinton and Prime Minister Tony Blair. The details of the last chromosome were published in 2006. Chromosomes refer to 23 pairs of organized structures in the nucleus of cells, containing DNA and proteins.

There are many interesting lessons to be learnt from the structure and function of the human genome, which refers to the entire hereditary information encoded in DNA. We now know that humans have about 30,000 genes instead of the 100,000 we estimated previously. For many years, scientists focused on the products of genes, which are proteins. However, we now know that many genes do not make proteins at all. What then do they do? They regulate.

Proteins are the building blocks of all living cells. Proteins carry out essential cellular functions ranging from the structural integrity of the cell to the very type of cell, the functions of the cell and the timing of the death of the cell. Whilst some genes contain the code for making proteins via messenger RNA, other genes are concerned with the manufacture of another type of RNA, a smaller RNA molecule called microRNA. These small units called microRNA function to either repress the translation of messenger RNA or they actually destroy the messenger RNA as part of their regulatory, inhibitory function. What are the implications of repressing or destroying messenger RNA and what happens if these microRNA regulators go awry?

There are good genes and bad genes. Different types of microRNAs target particular genes. Some genes, called oncogenes, are involved in the formation of cancer and can be seen as bad genes. Other genes, called tumour suppressor genes, are involved in suppressing cancer formation and can be seen as good genes. If a particular microRNA normally inhibits a gene that causes cancer (a bad gene), a reduction in the quantity or function of that type of regulatory, inhibitory microRNA will allow overproduction of the cancer-causing, bad gene. This is equivalent to a reduction in the quantity or function of the police, allowing the criminals to run riot.

Conversely, if the microRNA normally inhibits genes that suppress cancer (a good gene), excess activity of this type of microRNA will greatly inhibit the cancer suppressor gene and lead to cancer because there is little or no suppression from the cancer suppressor gene in the wake of its excessive inhibition from the regulatory microRNA. This is the equivalent of having a regulatory human rights watchdog group overseeing the suppressive actions of front-line, crime fighting police officers. The group functions so exceptionally well in inhibiting the over-zealous front-line police officers, the police complain that their hands are tied. The criminals not only run riot, they laugh all the way to, in and from their own bank.

The discovery of gene silencing through repression and destruction of messenger RNA by the use of regulatory microRNA was so critical in the field of molecular medicine, the discovers, Andrew Fire and Craig Mello were awarded the Nobel Prize in physiology or medicine two years ago, a mere eight years after they published their work in 1998. There is an irony in this seemingly new universal logic, this singular common sense, this theory of everything that runs through and links all branches of learning including economics and medicine. The basic principles involved here are as old as the hills. These principles are open knowledge and common fodder for any sorcerer’s apprentice and for any common, street-smart criminal who, as the don of an enslaved, drug-dependent, West Indian community, has been awarded far too many noble prizes.

(References: Robbin’s Basic Pathology by Kumar et al, 2007 &

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