Notebook: Circumcision as Lucky Charm

A very long time ago in my search for validation of my growing belief that God was a rather implausible and fanciful idea, I remember coming across a piece in some foreign journal that expressed astonishment at the disconnect between the professional lives and religious lives of Los Alamos nuclear scientists. Apparently some Godless European was incredulous at this greater insolvable problem than the mystery of splitting the atom. How could Ph.Ds spend their days dissecting the toughest theoretical and practical problems of the molecular world and their nights believing in mythological tales of creation and some sentient, eternal being in the sky and not suffer some mental break?

Richard Dawkins expressed this paradox by way of explanation. He said in his book, The God Delusion, that religion must have served some purpose for uniting mutually dependent bands of people in allegiance, identity and hope that ensured the survival of the species -- or at least the bands that took up such beliefs. His conclusion in light of the great suffering and destruction done in the name of religion, particularly Abrahamic religions, is that it is time to retire the meme of religious belief. Perhaps he is correct. But surely some other destructive force will fill the void as people in the main still need some tie to bind them to one another -- and means with an element of destruction and sacrifice seem to be the most effective so far.

To many, male circumcision represents a great hope to humanity. It is a hope that correlates with the great hope that crystallized in the coincidence of some animal or human sacrifice and the lucky salvation of the people who practiced it. (Think Pavlov ...) In those rituals, nothing real was achieved outside of the minds of the practitioners. In reality, a net loss was realized in the loss of the person or the animal. But the sacrifices lasted many multiples of time longer than people have enjoyed the modern era.

The data is pretty clear that circumcision damages the sexual lives of the men who suffer it. This is a truism that has been poorly studied, but amply anecdotally expressed in the internet age. It is done largely without consent, imposed by cultural authority on subordinates, and varies widely in its physical and destructive form. Yet its value remains in the minds of those who have suffered it, and in those who see salvation in it because they are so desperate or so forsaken.

The following article makes the case that HIV/AIDS is a "Darwinian event." A vaccine may never come. The virus works its destruction too slowly to ever "burn itself out" of existence. Except for the rare "elite controllers" and individuals with some mysterious immunity, no biological adaptation is possible for the great majority of individuals. Instead, it will be cultural adaptation that contains HIV.**

In the developed world, people will defeat the disease by learning to avoid and prevent it. Condoms used in more and more intimate settings are an adaptation. Serial monogamy is an existing adaptation in most of the world and one that will be adopted in sub-Saharan Africa where it is rare. Rapid and frequent testing is an adaptation. The article lumps male circumcision in with the others as an adaptation. Of course, male circumcision is not a protection. But it fills the human need for lucky sacrifice to ensure success.

Therefore, as condoms and monogamy take hold, education and testing seeps into the consciousness and routine of individuals, and as some populations are persuaded to embrace male circumcision, the poorer African communities that have been targeted won't really know what's containing the virus. But they will leave nothing to chance and continue to embrace it all.

Meanwhile, people outside Africa will likely use their own adaptations, condoms and testing, to contain the virus. They won't need male circumcision because they already know success without it -- and they aren't dependent on the United States or as dominated by it. The levels of infection have leveled off long ago and begun to decline in most of the world. The great epidemics in China, Southeast Asia, Latin America, and Eastern Europe, predicted in the first decades of the disease will likely remain predictions. But the reality will be something different. America and Africa will be alone in their dogma of destructive sacrifice for success.

**This is probably not true. However, in our fortunate age of advanced medicine and instantaneous communication, the biological processes required over generations to develop an innate immunity will likely never get the chance to occur.

Enjoy the Globe & Mail article below the fold.

A setback in the quest

A vaccine against HIV infection is one of the holy grails of research -- and is proving almost as elusive.

Late 2007 saw clinical trials of the world's most advanced HIV vaccine, by pharmaceutical company Merck, brought to a premature end. Not only did the candidate vaccine fail to protect people against HIV, it might have increased their risk of infection.

Millions of dollars and more than a decade of intensive research failed to produce a succesful biomedical protection against the deadly virus. Microbicides, vaccines and diaphragms failed to prove their effectiveness in advanced clinical trials. The notable exception is a public health measure that has stood the test of time -- male circumcision. Researchers are taking on a novel, formidable and poorly understood enemy.

The virus is a tiny pathogen consisting of nine genes packaged in a shell cannibalised from human cells. It has two key weapons: it disguises itself as human genetic material and it constantly mutates, dodging the immune system's attempts to fight it.

It has the advantage of remaining largely obscure. No one is known to have recovered from HIV infection and so scientists are unclear about the immune response at which a vaccine should aim. For HIV human genes are a place of replication and safety. The virus cannot reproduce on its own and so, once inside a cell, it heads for the nucleus. There it cuts open the twisting spiral of human DNA, chemically ties itself in and lets the diligent cellular repair mechanisms neatly fill any gaps.

Tucked into the cell's chemical core, it can lie latent and safe from the hunters of the immune system circulating outside. The human immune system has two strategies for dealing with infections. One makes antibodies, which block or inactivate invaders. The other uses killer T-cells to attack and chemically blast apart infected cells identified with the aid of helper T-cells -- also known as CD4 cells because of a prominent chemical component in their cell surface.

In a particularly diabolical twist HIV likes to invade the CD4 cells. Any vaccine that stimulates a response by infected CD4 also risks stimulating production of more HIV.

A therapeutic vaccine has to encourage T-cells to kill infected cells with active HIV, preventing HIV infection from progressing to Aids.

A vaccine that prevents HIV infection must stop the virus from implanting itself in human genes, where it lies latent.

Such an antibody-based vaccine could block those parts of HIV that bind to cells, theoretically leaving the virus futilely bumping between the cells, unable to replicate and vulnerable to the body's clean-up services.

But killer T-cells would still be needed to finish off any virus that managed to escape the antibodies, as well as any virus particles that could avoid the antibodies by spreading from cell to cell. Vaccines use dead, weakened or dissected pathogens to prime the immune system so that, when the real disease arrives, the body's response is swift and effective. But with a virus such as HI, which can insert itself into human genetic material, using a whole virus, even a dead one, is risky.

So scientists use dissected bits of HIV. The most obvious pieces to use are the spiky surface of the free-floating virus -- but this is the most mutable part of HIV, so it might simply avoid the immune response as its shape alters.

As a result potential vaccines have to trigger responses to the virus's less variable internal parts. Today powerful computer programs use graphics to design molecules which will attach to potential targets on HIV, much in the way that architects build townhouses.

Unfortunately, this is still something of a hit-and-miss affair because precise molecular engineering requires more knowledge of HIV than is available. Not only does HIV mutate constantly, but the viral population within a person evolves over time, altering the method of attack and discriminating less about which cells are invaded, used and destroyed. A vaccine that works at one point of HIV infection might be less effective at another.

Another problem facing researchers is how to detect which vaccines are likely to work before starting costly and time-consuming, full-scale clinical trials. One signal that a vaccine might be working is a strong response from the immune system. Alas, the Merck vaccine showed that a strong immune response does not necessarily mean increased protection against HIV.

The Step trial -- the South African branch was known as Phambili -- was halted late in 2007 after interim analysis indicated that the vaccine did not provide protection. More detailed analysis suggested that receiving three shots of the vaccine might actually increase the infection risk -- although this could be a statistical glitch. If there is increased risk, it appears to be greatest among people with stronger pre-existing levels of antibodies against the vector carrying the HIV proteins in the vaccine. If, or why, this vector can increase risk of HIV infection is still under debate -- but, without a firm answer, the closure of the Step trial has had a chilling effect on vaccine research.

Not only was the Merck vaccine the leading candidate, but the same vector is being used in other potential vaccines. Easy to genetically engineer and grow, and prompting strong responses from several different parts of the immune system, it appeared to be ideal for the job of vaccine transport.

The failure of the Merck vaccine dampened the mood among researchers. To boost their morale, some are turning to the oration of a fighter from another age.

Presenting a slide, one of them quoted former British prime minister Winston Churchill: "Courage is going from failure to failure without losing enthusiasm."

The evolution of a killer

HIV is influencing the social and cultural evolution of human societies and will eventually alter the genetic pool in populations where the disease is rampant. This argument was put forward by Professor Alan Whiteside of the Health Economics and HIV/Aids Research Division, University of KwaZulu-Natal, and Alex de Waal of Harvard University in the latest Southern African Journal of HIV Medicine.

Acknowledging that hard data on the issue is still sparse, Whiteside and De Waal contend that HIV is a Darwinian event, which has an evolutionary effect on human beings in three interlinked ways -- directly through genes, through cultural adaptation and through changes in the ecological framework of human beings. History of epidemics shows that some people or populations might have higher, or lower, susceptibility to a disease than others and that these differences might result from evolutionary pressure exerted by other infections.

Ramifications from the plague might still be echoing because the bacterium Yersinia Pestis killed an estimated one-third of Europeans. People with the genetic edge, which enabled them to survive that biological holocaust, might have some resistance to HIV.

Conversely, the huge effect of the virus in sub-Saharan Africa could be because Africans have not undergone plague-driven genetic selection. In the same way genetic resistance to HIV might cause a long-term evolutionary impact on genes among human populations with very high levels of infection. Such effects, argue Whiteside and De Waal, could be behavioural because body chemistry influences human behaviour.

A feature of HIV in sub-Saharan Africa is that it sickens and kills adults. So the virus could be exerting evolutionary pressure in favour of people entering puberty and reproducing earlier. It could be causing cultural adaptation favouring populations where early reproduction is encouraged or male circumcision is practised. The effect of HIV on human culture and environment is a demonstration of Darwinian pressure on "memes", say the two social scientists. Memes are theoretical units of information, such as songs or religious belief, that combine to create culture.

A concept initially developed by evolutionary theorist Richard Dawkins, memes "live" in human brains and are analogous to genes in that they respond to competition, vary during interpersonal transmission and mutate. HIV's Darwinian effect might promote memes such as monogamy, which would be more advantageous than the meme of having multiple sexual partners.

Whiteside and De Waal say there is little evolutionary pressure for HIV to lose its lethal nature, because of the long period of infectiousness before the onset of Aids. The virus kills over such extended time that the epidemic is unlikely to burn itself out unless there are behavioural adaptations or a vaccine. The two writers also highlight the potential evolutionary effect of HIV on other pathogens, because a large population with weakened immune systems encourages other diseases. Even microbes normally kept in check by vaccination might seize the opportunity to mutate and evolve in immune-compromised individual systems before spreading.

Reference

Bereford, Belinda. A setback in the quest. The Globe & Mail (Canada). January 7, 2007.

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