Results of Grid

Total Run Time (y:d:h:m:s) (Rank)	0:010:05:36:52 (#416,376)
Points Generated (Rank)	33,318 (#322,072)
Results Returned (Rank)	156 (#265,801)

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.  

Relevant Journal Article

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026100

Interview Responses

Haddy's Response

1. Describe your feelings about or response to the interview.

 

I have known Cody for about two years, and when I heard about the news of his cancer, I was devastated. It seemed almost impossible to me that something like that could happen. After he returned to school I was glad he was there and talked to him like normal. I felt uncomfortable bringing up what he went through to him feeling he had had enough of it, and I think he knew. I fessed up to him before the interview that I was uncomfortable about asking him about his cancer. He was very understanding, so understanding I felt rather foolish for not talking to my friend without the excuse of the interview earlier. After the interview I had an appreciation for what he went through and it made me stop and think about what he and his family must have gone through.

 

 2. What changes occurred for you as a result of your interview?

The interview made me realize that no one is immune to life. Often times I just go on autopilot and the days mesh together. I hated that I was doing that.

 

3. Did anything about the interview disturb you?

I was only disturbed by the fact that I had not had a previous sit down with Cody

 

4. Describe the connections you found between the interview and your research & classwork.

 

I like the grid and think it’s a great idea. Talking to Cody reaffirmed how imperative it is to help in these types of research. Before it was an assignment I could feel good about. After the interview it added a level of emotion I was lacking.

Phu's Response

1.     I was not present when the interview took place. Jack and Haddy knew Cody personally and they thought it would be awkward for someone Cody didn’t know to be there for such a personal topic, and I agreed. However, while I was listening to the recorded interview, I felt almost awestruck at how calm Cody seemed to be even after everything he went through. I could also feel that he genuinely wanted to help others in his situation when Jack and Haddy asked what advice he would give to others.

2.     Although I already knew that cancer isn’t an instant death sentence anymore, when Cody said it in the interview, it was like it had a lot more weight to it. To me, it reaffirmed how far cancer treatments have come and how far they will advance in the future.

3.     The disturbing part of the interview for me was when Cody was describing his hospital visits. It made me realize that while the treatments are more advance, the procedures themselves are still rough on the patients.

4.     I believe that our grid that aims to conquer cancer through x-ray crystallography is a step in the right direction for cancer treatment. Since cancer is different for everybody, x-ray crystallography will hopefully lead to better cancer treatment regiments that are tailor-made for people, kind of like how a nutritionist made a custom diet plan for Cody.

Jack's Response

1.     Describe your feelings about or response to the interview.

Since I know Cody on a personal level this interview really hit me pretty hard. He had sent all of us in pike updates about how everything was going during the fall semester but it really didn’t sink in until I heard it from him. Just hearing him talk about it made it seem so much more real to me then just reading an email about it. You could hear it in his voice how much it has affected him and his family and how much pain he had actually been going through. It was a very good interview and I wish I could have talked to him about it this in depth with out it being mandatory for a class. I felt ashamed but I was glad I got a chance at all to make it happen. It seemed like such a life-changing event such as cancer can hit anybody after hearing him. We all live in such a closed world of our own that stuff like this can only happen to people we don’t know.  The interview was a real eye opener to say the least.

2.     What changes occurred for you as a result of your interview?

One thing that really struck me was how much he had to change his diet. He said in the interview that it was hard for him to understand why people wouldn’t change something like this if they really had a will to live. It really makes you think when you eat something that isn’t great for you what kind of effect it will have on your body. Hearing this really opened my eyes on using nutrition for medical care. It really fascinates me how much we rely on drugs when changes in diet can increase health quite a bit.

3.     Did anything about the interview disturb you?

The one main thing that disturbed me about the interview was how much he was struggling getting back into the swing of things. I’m sure he knew it was going to be difficult getting back into it but to the extent of what he is going through it is pretty amazing. He has some real dedication and hopefully he makes it through the rest of the semester with out any more problems.

4.     Describe the connections you found between the interview and your research & classwork.

Since our grid is on helping to find the cure for cancer it was quite evident that people that are not affected by this terrible disease can help out by just downloading a computer program. Since Cody is only a patient and not an expert in the field it was hard to tell how much of a difference it could actually make but doing something for people like this is always a good feeling. 

Interview with Cody Schuler

The other day some of our group members interviewed Cody Schuler, a fellow Rockhurst student who was recently diagnosed with renal cell carcinoma, aka kidney cancer that had metastasized to his bones and liver. This was a difficult interview to conduct because we know him on a personal level and had known what he had gone through. Cody made it very easy for us however, and was very open about his whole experience.

Cody was unsure exactly what grid computing was, but after explaining how the Help Conquer Cancer grid links multiple different computers together via the internet to improve the results of protein X-ray chromatography, and how that would improve their understanding of cancer initiation, progression, and treatment, Cody replied, “That’s definitely a good way for the average Joe to get involved.” Cody emphasized that sometimes people who donate money do not know exactly what it’s going for or what the process is. They are uncomfortable donating money because they can’t see a direct correlation between their donation and impact.  This is why he thinks that grid computing could be a great way for people to get involved that would be of little or no inconvenience.

Cody was diagnosed back in August 2011, and when asked what he felt when he was first diagnosed, he said, “It was shocking. It’s so far away now it feels like… when I think about what that felt like, it feels like it was like a different lifetime.” Cody did not go back to school that semester, but said that the diagnosis really brought his family together. 

As for treatment, Cody has undergone hypofractionated radiation therapy, where a lot of radiation is given in a short amount of time. Supposedly this worked faster, but had more risk of damaging good tissue and lead to Cody’s hair quickly falling out everywhere they administered the treatment, to which he responded, “Small price to pay.” Cody has also received some mild chemo and antiangiogenic drugs, which prevent new blood vessel growth, thereby cutting off tumor vasculature to prevent their growth and spread. Cody had been on no other medications up until last week, when pain and intense headaches sent him to the E.R. K.U. Cancer Center gave him some steroids and painkillers, which have been keeping inflammation and pain away with only some minor sore leftover.

Cody has also undergone several surgical procedures. One was an angiogram embolization, which involved using tubes to cut off the blood supply of the tumor. This took two days, seven hours each day, and on the third day they were able to remove the tumor. The next procedure was a few weeks later when he had a skull plate put in. The most recent procedure was the removal of one of his kidneys. When asked what he was thinking when going into surgery he stated, “… I didn’t really have time to think about it because by that time you’re so dazed and confused, you just go and do whatever they tell you to do.”

For Cody, one part of the treatment process that really stuck in his mind occurred during his first stay at the hospital for his first few surgical procedures. He had been under anesthesia for a combined 24 hours in a three day period. “[When you get that kind of general anesthesia and you’re, like, knocked out for that long, when you wake up it’s hard to sleep. And when you do sleep you have nightmares. So I was having nightmares and, on top of that, I was in a lot of pain.” This combined with an environment of constant poking and prodding from medical personnel was the toughest part of the process for Cody.

Cody’s advice to others around his age that get diagnosed with cancer is to first not panic. “It’s not what it used to be. Cancer still has the same connotation, but there are a lot more treatment options now and a lot more people - a huge number of more people - surviving it.” Second, he tells them that a lot of this situation is in your control. “It’s how you make it out to be, so you need to stay positive first of all.” Finally, if you seriously want to survive, to make the most of treatments, and to avoid as many side effects as possible, Cody says you have to change your diet. Cody himself went to see a nutritionist who took into account several factors such as his blood type, genealogy, age, etc to create a specialized diet for him. Cody stressed that this is an important consideration for anyone dealing with a serious illness.

Overall, Cody feels that his experience with cancer so far probably hasn’t changed him enough since he still gets stressed out over things like school. But, he does admit that now he doesn’t care as much about what people think anymore. “I’m going to be myself and I’m going stick up for what’s right […] No point in stressing myself out and compromising my values to fit in.”

Even though Cody is busy with school and treatment, he still took time out of his day to speak with us. He was very hospitable and open. We greatly appreciate his time and wish him the best.