Wednesday, May 31, 2006

The Fossils Within Us

Cancer is viewed by most people as an accident. Something happens to turn cells bad. The view that I’ve had is that it is indeed an accident, but in fact many accidents, accidents filtered by the natural selection of the body itself. But things are a lot more complicated than I, and many others, have thought.

Presumably the body has many defenses against cancer – DNA correction processes, cell suicide, immune system responses, cell senescence, who knows what else. The result of these mechanisms is that we are probably "cured" of small cancerous events many times, maybe countless times, during our lives. The body is a paragon of self-correction, and why is that? The reason we can fix ourselves is that our ancestors were subject to natural selection pressures. Replication, variation and selection equals change, adaptation, fitness.

Pathogens are subject to the same forces, both within our bodies and within a population, filtered by the body’s defense mechanisms and by barriers to transmission. HIV is the customary exemplar of this concept. It is not particularly good at accurate reproduction, so it produces many bad copies, some viable. These copies are differentially resistant to or hidden from the immune system. The immune system adapts, since it is designed to work according to the same evolutionary rules, but it cannot keep up with the rate of variation for this pathogen. Each partially successful attempt at wiping out the virus just makes the surviving virus more resistant to your best tricks.

Our culture provides us with additional defensesmedical intervention, behavioral changes, research. Such tactics are extensions of and supplements to what the body tries to do, and the effortshave the same general impact on the virus. It changes. It adapts. The memory of RNA, (DNA in other pathogens) carries the successful adaptations. The copy errors induce new random changes, the sheer number of which are likely to create new adaptations. (This is why the viral load issue is so important.) So far, HIV is outsmarting us, individually, as a species and as a culture; but we are also very clever and won’t give up.

Cancer, as I have understood it, seems to follow the same scenario. Cancer cells reproduce without limitation and have sources of variation. Each of our defenses, each medical effort, each partially successful treatment, leaves some survivors. These survivors, although not as virulent as the original population perhaps, will be more resistant, thanks to natural selection, to our defenses. Unless completely wiped out, they will eventually destroy us.

There are two interesting aspects to cancer that make me question this understanding. 1) The defense mechanisms that a cancer develops can be extremely sophisticated, as noted in the BBC link . 2) Cancer, although it manifests itself with great variety, has customary, diagnosable types. There are recognizable syndromes, classifiable cells, predictable patterns. Now, the cancer cell has access to our entire genome, every protein, every trade secret from our distant past. It can, theoretically, reorganize these resources in any way to put up a defense.

We know that it can evolve, but it seems unlikely that it can evolve that fast, within a single person in a single lifetime. Do we think that it can be transmitted and thereby gain multiple generations to evolve more sophisticated responses? There have been arguments in the past that viruses cause cancer. There is some connection with viruses. Certainly HPV can induce cervical cancer. But are these viruses actually transmitting the cancer or merely triggering a latency? It seems from statistical studies that many triggers exist. Only 15% of cancers are related to viruses, and often a cancer can start with no apparent trigger at all. There is also no evidence that cancer, per se, is infectious. So it seems to me unlikely that the memory of the cancer can extend past a single human except through the human’s own genome.

The implication here is that the sophistication of cancer is pre-packaged somehow, that certain versions are more likely because of a predisposition. I think it could be akin to a common mutation. There are genetic configurations that are unstable for some reason. Such genes can change easily and frequently to a particular mutated, but nonlethal, form. As I remember, dwarfism in humans is the result of such a mutation. They can also change to a lethal form. Could cancer just be a predictable mutation of somatic cells?

A second possibility is that the virus is taking advantage of human reproduction to reproduce itself. Some viruses do insert themselves into host DNA. The virus is perhaps getting a free ride, like parasites on a fig wasp, but if there is no independence, then the virus loses its incentive to pursue any interest other than the host's interest. If there is no transmission to new hosts other than through the host, the only excuse for damaging the host would be incomplete integration, which implies that the virus would not yet have sophisticated host-specific defense mechanisms.

The other possibility, which is dancing in my head since I read the BBC article, is that there are pre-evolved sequences hidden in our genes which represent ancient alternative paths of development. Think about that for a minute. We may have evolved mechanisms to quash life-stages that were necessary at some point in our pre-history when our ancestors were axolotls or chordate worms or multi-cellular colonies of who-knows-what. When these incompletely eradicated pathways are fortuitously invoked by the afore-described micro-evolutionary process, it might lead to a stereotypical sequence of events. That is, inappropriate tissue development takes place that may have been appropriate in another context. Since it is almost normal by that standard, it proceeds unchecked.

5/30/2006 12:13 AM

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