Curated Paper 2 - Austin Martinez

Curated Paper 2

Someone said to me yesterday, “Isn’t it interesting how our bodies are literally one large chemical reaction?” When you take a step back and look at the body as a whole, it is astounding how connected it is. We like to compartmentalize the body: the head, the torso, the limbs, and so forth. Yet, like a central ecosystem, our bodies are large communities that interact and, when something happens in one area, the effects cascade throughout. This is how we can link such different portions of the body such as the central nervous system, the digestive system, and the tiny strands of DNA that link it all together.

The brain is, without a doubt, one of the most mysterious and intriguing pieces of the body. Its anatomy is functionally magnificent, its biochemistry is in depth. In our discussions on the brain, I really feel that we were able to pull together the anatomical and biochemical aspects of the brain. I had heard of many of the diseases we had discussed in class, but I didn’t ever really understand how they worked, or what they were. Many of these I lumped into the same category, of course knowing they all had different mechanisms of action, but somewhat ignorantly thinking, “Parkinson’s? Huntington’s? Creutzfeldt-Jakob? They’re all pretty much Parkinson’s.” It was outstanding to be able to cover each of these diseases and really find out that they are all extremely distinct in their presentation, which also makes them distinct in treatment options.

As we discussed the mechanism of these diseases, in conjunction with ancillary research this prompted on my part, I was actually, finally able to understand how these brain diseases develop. For example, Alzheimer’s. I knew that there was an issue with Tau protein deposition, but as I went on I came to realize that there are really more than one hypothesis surrounding Alzheimer’s. The majority deal with protein deposition, specifically how during the folding process the alpha-helices are clipped and beta sheets are clumped together. Using the knowledge provided in this class, as well as others, I was now able to understand how these diseases actually occur.

While I am not planning on specializing in the brain, I am preparing to be a doctor. I’ve been accepted to medical school and plan to focus on orthopedic surgery, if I match with that residency. Although that is a musculoskeletal field, this same principle applies – it isn’t simply learning the symptoms of the disease; those mean little if you don’t understand the principle behind it. It applies to the skeleton as much as it applies to the brain. Understanding the normal mechanism for function in the skeleton helps you recognize much more than understanding the symptoms of abnormality.
I was able to take this same method when looking at the other diseases we approached, including Huntington’s. Upon hearing about its genetic approach, I was able to apply things I had learned in Genetics to gain a deeper understanding. Not only did this understanding come as we discussed brain diseases, but also as we discussed traumatic brain injuries. I found it shocking, yet reasonable, how so many social aspects of a person’s functioning is altered by a physical change in the brain. One of the locations in the body that has plenty of room for exploration is the gut. On first appearance, the gut appears to be fairly straightforward - it’s a tube that functions in secretion and absorption for digestion. It wouldn’t appear to have much effect on how the rest of the body functions, but this is actually false - the flora of bacteria in the digestive system have an outstanding affect on what the rest of the body feels. 

This was probably as telling as finding a positive correlation – by having evidence supporting no difference with microbes and parenting, this still reveals a lot about how the behavior of people and animals are influenced by the bacteria in the gut. Rather than having a correlation to the gut, this difference in parenting was genetically linked instead of environmentally linked. This was significant because it defines the boundaries of what microbes do and do not change.

There is a delicate balance of the gut bacteria. They function in the digestive system for many cellular and metabolic processes that cause changes in hormonal flow through the body. We read an interesting article regarding the microbe of the gut and stress hormones. Society as a whole is stressed out – taking this back to our discussions of the brain and mental disorders, it sure seems like a large portion of the populace is influenced by anxiety, depression, and other mental disorders. Of course people don’t choose these, but it does make me wonder, what ties are there to gut flora and mental condition, as it relates to what we put in our food? For example, if we have eating or other environmental habits that affect our gut microbe, is it having not only an effect on the stress response, but also other mental responses we don’t quite know about? Bringing it back in, there was a positive correlation found between gut microbes and stress. Perhaps the most significant finding was not just this correlation, but also that parenting was not positively correlated to the gut microbe.Genetics then positively affect the microbiome, which in turn affects hormones, which then affects the brain and all the other systems of the body. Perhaps this makes it a bit more clear as to how all of these biological systems are connected - a change in one has a “domino effect” on changing other systems. The body is not so singular as we like to think - its complexity is far beyond even our imagination. This links everything back to the genome. Genes are natural - everyone has genes that code for who they are. With the advance of technology, we now not only understand genes, but also that they can be changed. That is both an intriguing and scary thought. 

Another aspect of this is how does gene therapy affect future generations genomes? Certainly we don’t claim to understand all aspects of how gene therapy affects the body. It is a new technology, and many more things will be revealed about it. But if we alter someone’s genome, what will that do to subsequent offspring? Returning to Down Syndrome, individuals with this disorder cannot produce fertile offspring. If we were able to edit their genome so that they could produce fertile offspring, would the offspring be unaffected? Would they be physically and cognitively complete? Of course we don’t understand these questions yet, but they are things we will have to think about in the future.
I did enjoy that the aspect of ‘playing God’ was explored in our discussion. I feel as though the points that were brought up were fair, and that most people believed that there is a point in science that is too far, stepping beyond the nature or God. The technology is fantastic, but it really is the ethics that need explored. One major genetic disorder that we discussed that could be handled is Down Syndrome. There are many other disorders similar to this, but this was one we discussed in class and that everyone is familiar with. Not only are these individuals experiencing shortened life spans, but also many physical and mental problems as a result of the chromosomal errors. I do think we could use gene therapy to help these people; however, I love these people as they are (I think everyone does) and by fixing Down Syndrome in one person, I think that could cascade into fixing the syndrome overall. We seek to eradicate disease in other ways - for example, the influenza virus. We recognized that it could be prevented and took action, and today influenza kills far less people than it did a hundred years ago. The difference is that treating influenza, or problems like it, don’t necessarily alter the genome and also are made post-birth. This is where the ethical issues arise with genomic alterations in gene therapy - they alter the actual DNA of an individual and it is done pre-birth. Anything done pre-birth is controversial, as we see with abortion. 

And that is the goal. To know more about how these things cascade into each other. It is imperative for future medicine that we connect these things - I hope I live a lifetime to see many more mysteries unfolded. The topic of eugenics was brought up - “cleansing” the genome to make a master or purified race. I don’t know that this is an entirely apples-to-apples comparison, but really isn’t gene editing the same? Clearing out the undesirable genes? Perhaps not in the same way that WWII horrors presented it, but similar. Some way I can see a superseding to this ideology would be in the interest of saving lives. If an unborn child was not going to survive, and we could help them survive by gene editing, I could see this as a profitable case. There are many considerations to be taken - once again, would the child be able to function and lead a normal life? I think we need to understand more about gene therapy and that it could possibly be used for good when we know more.