Questions

11.   State each of Darwin’s four postulates. Fully explain how the generation of treatment-resistant cancer cells meets each of the four postulates for evolution by natural selection.

The theory of Natural Selection as put forth by Charles Darwin includes four postulates. First there is variation among individuals of the same species. Second, at least some of these variations are hereditary. Third, in every generation, there are more offspring produced than can survive. Fourth, natural selection operates on populations; meaning survival and reproduction are not random. Individuals with favorable adaptations tend to out survive and out reproduce others who lack the trait.

In much the same way that Darwin’s Postulates can be applied to HIV, it can be applied to cancer. Cancer is the unregulated over growth of cells in the body. There are many causes that can be attributed to cancer; among them are mutations, viruses, and even environmentally triggered genes. If a mutation, or a virus, or a genetically ‘turned on’ cells is turned on to cancer and replicates without control, it is likely that it will pass on its deleterious trait to its daughter cells and they will pass it on to their daughter cells. In this manner, these cells are separate from the other non-cancerous cells of the body and can represent a unique population in that they grow without control. However, we know that even in normal cell division, mutations arise. This does not exclude cancer cells. Thus the ‘immortal’ dividing cancer cells introduce variation into their daughter cells when they undergo mitosis. This introduces variation among the cancerous cells. In this way, Darwin’s first postulate is satisfied. Because cancer can be attributed to genes, and these cells are undergoing mitosis, some of this variation that occurs is passed on to more cancerous cells. This means that even though these cells are all cancerous, they are not all exactly the same, and this variation can be heritable. This is where treatment problems arise. Certain drugs target certain features in cancerous cells. For example, some drugs target signaling pathways that promote growth, others block receptors, and the list goes on. Since we know that not every cancer cell is the same, they are not all affected in the same manner and some survive the onslaught of the cancer drug. These cancer cells may then pass on their heritable qualities that allowed them to survive the attack of the cancer drug, and this is how cancer resurfaces. Postulate three meets this scenario. There are more cancer cells produced than can survive due to cancer treatment. Those that survive have a special adaptation that has allowed them to survive treatment. They can then pass on this favorable feature (favorable for the cancer population, not the individual), which is then selected for among the population of cancer cells. In the next generation, the cancer cells susceptible to the cancer drug have been destroyed while resistant strains survive and increase in frequency in the body as predicted by postulate four.

2. The authors repeatedly assert that therapeutic resistance in cancer is fundamentally an evolutionary process. Why, then, do you think the authors found such scant mention of evolutionary concepts in the cancer literature? Which of the three reasons on pages 6 and 7 do you believe are most to blame? (In answering this question, consider the way science was portrayed in the movie “Flock of Dodos.”)

The psychological barriers, that is, the misconceptions and even negative reactions from the public, as well as the lack of evolutionary thinking in medical professionals, definitely play a role. However, I think the lack of evolutionary concepts in papers involving cancer stems from the lack of evolution education. Without learning about evolution, of course it would be difficult for medical professionals to apply evolutionary concepts in their thinking. Some evolution education would go a long way in changing the way medical professionals think and can even clear up many of the misconceptions people have about evolution in general.

3. Why should a doctor understand evolution? To fully address this question, read “Health and Medicine” (Futuyma 2005) under “Service Learning” on WebCT.

It is very important for doctors to understand evolution because it can help combat infectious diseases. This can be seen in both antibody resistance and for vaccine development. Over time certain bacteria can be naturally selected since they are resistant to certain antibodies, therefore, when using the same antibodies for the infection it would not kill the bacteria. Vaccine development is also an important part of medicine since a new influenza vaccine has to come out every year because of the virus having so many strains from mutations over time. This can be seen in our paper because certain therapies for cancer are becoming resistant the second time around to patients. If the cancer returns, then these cancer cells that have returned are obviously resistant to the previous therapy and doctors would have to determine a new therapy to kill these new cells.

4. Consider the importance of variation in evolutionary processes. Why would it be important to evaluate the within-tumor heterogeneity in a population of neoplasmic (cancerous) cells?

This goes back to the importance of Darwin’s postulates. There is variation among cancerous cells just as there is among non-cancerous cells. Some of this variation is hereditary meaning it can be passed on to daughter cells during mitosis. Therefore, not every cancer cell is the same and is not susceptible to the same treatment. This is where failure arises in treatment. The mistake of lumping all cells in a tumor as exact replicas leads to the mistake of treatment that does not take into account the variation. If however it was possible to evaluate the within-tumor heterogeneity and match a treatment option to each specific variation all cancer cells will be targeted and not just the major susceptible group. Although this seems easy enough, it is not. There are millions of cells in a tumor that are dividing and introducing constant variation. Even if this variation were somehow identified, this would take a very specific drug to attack each cell.   

Bonus: Do you think med students should have to take an evolution class? Why or why not?

         From my own experience, I feel that taking an evolution class is absolutely necessary for med students to take. I have always accepted evolution, although my knowledge was limited compared to what it is now. It is through this broadened grasp of evolution that I see how much of an integral part of everything evolution is. Biology without evolution is physics without gravity. The same can be said of medicine and evolution. We have seen time and time again how this is true. Our textbook opens up with the example of how Darwin’s postulates play such an important role in HIV treatment and transmission. An outside example from class is the fact that we are facing a bacterial resistance to drugs epidemic. Basically what is occurring is due to the fact that not every strain of bacteria is the same, the ones that survive drugs flourish and pass on their genes. These resistant strains are no longer susceptible to our drug treatments. Had evolution and Darwin’s postulates been consulted this problem might not have ever happened. The paper we reviewed shows even more evidence of evolution in the medical field through cancer treatment. As an aspiring medical student myself, had I not take evolution I would have not even considered Darwin’s postulates when thinking of cancer treatment even though I do accept evolution.