In the Mayo Clinic in Rochester, Minnesota, a cancer patient is being treated with a new drug designed to help the body fight cancer.  Cancer cells are injected with a very specific biochemical created from a new technology called RNAi.  The chemical duplicates the gene that causes the cells to become cancerous but has the effect of actually turning off the gene which has caused the run-away growth that led to cancer.  The patient is able to slowly but recover from the disease, effectively healed.

Although this medical treatment is still being explored and is not yet applied in treating most diseases, the use of this technology is is being hotly debated in scientific and medical circles.  I first discovered the debate on RNAi after having watched a special on PBS’s Nova ScienceNow July 26, 2005 (http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html).  I learned how interference RNA (RNAi) plays a role in actually turning off certain genes when the cell detects possible invasion of a foreign body.  Yet it was not until I viewed the programs Secrets of the Dead: Mystery of the Black Death (http://www.pbs.org/wnet/secrets/case_plague/index.html) and Frontline: The Age of AIDS (http://www.pbs.org/wgbh/pages/frontline/aids/) that another idea came to me regarding the potential use of this technology to fight the HIV virus through limiting its transmission.

RNAi is the process whereby scientists inject double-stranded ribonucleic acid (RNA) into a cell or cells to stop the expression of a particular gene.  Thus, through advanced laboratory techniques, scientists can add an RNA strand for the color purple into a purple petunia.  The host plant identifies this foreign RNA strand as an attack (much like how a virus attacks a cell), thereby turning off the gene, in this case, the gene for the color purple.  The plant’s flowers will then be white.  RNAi is also referred to as inhibitory RNA, RNA silencing, or RNA inactivation.

Although I have been unable to ascertain whether or not researchers into RNAi technology and those researching CCR5-D32 in disease prevention have been able to, in essence, combine their research in the prevention of the transmission of HIV (human immunodeficiency virus) and the subsequent onset of AIDS (acquired immune deficiency syndrome), I believe that the potential for developing cures for this disease may be considerable. I believe it may be possible for scientists to use RNAi to “trick” the T-cells (involved in the immune system) into turning off the gene that creates the receptors which the HIV virus attacks, thereby creating a delta32 deletion without the individual having the need to be born with the mutation.

The study of the delta32 allele is most interesting.  This is simply a mutation among a small group of people that, in effect, helped those who possessed the mutation stave off the medieval Black Death.  Yet the Black Death, once commonly referred to as “the plague,” and HIV have more in common than many people may think.

A series of fascinating public television programs entitled Secrets of the Dead: Mystery of the Black Plague (http://www.pbs.org/wnet/secrets/case_plague/index.html) and Frontline: The Age of AIDS (http://www.pbs.org/wgbh/pages/frontline/aids/) really brought a revelation to me of the importance of random genotropic mutations in the continual, ongoing evolution of our species. In particular, I refer to the rise of the CCR5-D (delta) 32 allele in Western Europe and the part it has played in rendering the bacterial Bubonic and Pneumonic Plague and the HIV-1 virus impotent in causing fatality to the mutation's recipient.

It is a revelation, I say, because proponents of natural selection possess a nearly irrefutable example of how gradually an organism - in this case, Homo sapiens sapiens – under intense environmental pressure from microbial diseases – can experience change in their genetic structure, the coding for the very proteins which define a species and, ultimately, allow one to be susceptible or resistant to various genetic, bacterial, or viral diseases (http://ib.berkeley.edu/labs/slatkin/novembre/GalvaniNovembreMicInf2005.pdf).

The explosion of the delta32 mutation among human populations of Western Europe (a mutation of uniquely Scandinavian origin roughly 2000 years ago) was brought about by environmental pressure that began with the introduction of the plague in coastal Italy in about 1347. Geneticists have shown today that those individuals with the CCR5-D32 deletion mutation on one chromosome still contracted the disease but successfully recovered, while those carrying the mutation on both chromosomes were virtually immune to the plague's effects.

Interestingly enough, the HIV-1 virus attacks the immune system (T-cells receptors) in nearly the same manner as the plague, even though the former is a virus and the latter is a bacterium. Individuals who possess the CCR5-D32 mutation also show a heightened resistance to the HIV virus and even immunity in some cases. Because of these two infectious agents over a nearly 700-year period, estimates place the frequency of the mutation between 10 and 20 percent among human populations of European descent.

Today, given that the Black Death was relatively uncommon among the inhabitants of continents like Africa and Asia and among Native Americans in the New World, individuals from these ethnicities exposed to the HIV-1 virus are 1) more likely to contract it and 2) more likely to die from it once contracted.

Although the relative frequency of the CCR5-D32 deletion mutation is negligible among inhabitants of Africa and Asia, those few individuals who may have somehow inherited the mutation through a European ancestor will prove more likely to survive the AIDS pandemic, thereby increasing the incidence of the mutation even on these continents. I suspect that as the fatal HIV virus runs its course in the decades ahead (as all deadly pathogens eventually do), natural selection will globally favor those individuals who possess the mutation and its frequency in the human genome will continue to increase significantly.

Whether future unforeseen pandemics will place further environmental pressure favoring selection of the D32 mutation until the deletion becomes the genetic "rule" rather than the exception cannot be known with certainly; yet one thing that can be said with a measure of absolutism is that regardless of how far our technology and social institutions evolve, nature will continue to exert its influence on our species, subtle or otherwise. Natural selection is a real and vibrant force that will continue to operate as long as our planet can sustain viable life, enacting its own version, comparatively speaking, of genetic "uniformitarianism" and "catastrophism."

So, why is any of this important?  We as a species stand upon the threshold of genetic determinism, soon possessing both the ability and the will to construct through gene splicing future generations of Homo sapiens sapiens.  We will have the ability to splice genes for selected benefits such as intelligence and coordination while splicing-out genes that may predispose our descendents to diseases like Alzheimer’s and diabetes.  Still, for all the technological and medical precision we are developing, we may actually end up removing "bad" genes from our progeny's gene pool that may actually ward against new and deadly diseases such as HIV. 

Let's say that it's 100 years in the future, the turn of the 22nd century, and it is not uncommon for most couples and  individuals desiring to have a child to have their chromosomes spliced and arranged so that the subsequent off-spring is relatively healthy and devoid of most bad genes.  Additionally, let's assume that one of those bad genes, we'll call it the XYZ-Alpha mutation, causes humans to stop producing an enzyme that may cause pimples on the skin.  We don't, after all, in a world where we can create our perfect children, want they to have unseemly skin blemishes; that may cause them to be ridiculed and teased in school.  So, in this hypothetical example, it is standard operating procedure (excuse the pun) to remove any occurrence of this mutation from the gene-splicing procedure.  Except for those who are destined by poverty or simple choice to have children the  "natural" way (this will become increasingly viewed as a Medieval and Draconian method of creating offspring, to be sure), all other children will be genetically free of unseemly mutations and, therefore, less genetically diverse.  Then, it happens.  An arrival on the scene of a wholly new form of virus called, for argumentative purposes, ABC.

Interestingly enough, this new ABC virus attacks receptors on the XYZ allele, resulting in the prolonged and painful wasting away of the human victim from the outside in.  It is spread in a variety of ways but is primarily a blood-borne pathogen that is exchanged through the transmission of body fluids.  It began in developing nations and has been transmitted to three continents before the World Health Organization was able to identify the disease.  Since the virus has a dormancy period of 10 to 20 years, health officials have no idea what the true infection rate is since the dormant virus does not appear in any currently used blood pathogen tests.

In no time at all, wealthy, gene-spliced, jet-setting adults and children alike have contracted the disease both on vacations and on selfless humanitarian missions overseas, bringing the disease home with them and spreading it among the general population as well as their gene-spliced peers with whom they typically socialize choose as mates (class begets class).  These near perfect, attractive, intellectually and physically gifted individuals are decimated by a disease that spares few who do not have the XYZ-Alpha mutation.  In essence, because of the lack of foresight of those who would genetically recombine humans so that they are void of predisposition to diseases and other bad genes, attempts to create whole, healthy children leads inadvertently to their death.

As we develop the techniques and the expertise to create gene-spliced offspring, I believe that we should consider our choices and weigh the potentialities with the inherent risk of the unforeseen.  Just because we possess the ability and the power to do something does not necessarily mean that we should do it, at least not after careful deliberation and an ongoing, global forum on the ethical implementation of technology, particularly that which could alter the very evolution of our species. 

There are, though, hurdles that I imagine must be overcome in order to create such a treatment.  Recently, the National Cancer Institute noted that in human test subjects, cells eventually developed a resistance to RNAi treatments (http://www.cancer.gov/ncicancerbulletin/NCI_Cancer_Bulletin_010306/page5). Until this field of research is fully tested and problems overcome, it may still be some time before effective, long-term medical treatments utilizing RNA interference technology become common place.