Brain, Microorganisms, and Gene Therapy

Ashley Garcia

BIOL-4500

November 16, 2018

           The central topic of our class is Ayurveda and balance. In high school biology we are taught that our body tries to maintain homeostasis through different processes, so from a young age, we’ve known that to function properly our body needs to be in balance. And in this class, we see how everything is connected and contributes to our health. Initial it was hard to see who our brain, microbiomes, and gene therapy are connected. However, after discussing these topics in class the connection between them is more obvious.

Brain  

            The brain is kind of a mysterious organ. We have a lot of information on the brain, like certain lobes of the brain are responsible for certain skills and processes, that nerve cell in the brain communicate via electrical pulses that are assisted by chemical signals, and the right side the brain controls the left side of the body and vice versa. But there is so much more that we still don’t understand. Like how information is encoded and interpreted, why people sleep and dream, and how our personality is decided by our brain. I also find it fun to think about how scientists run experiments on other brains to understand them and it was their brain that came up with the and can interpret the results; it’s like some weird inception. And since the brain is so mysterious it makes understanding how a disease affects the brain more difficult.

            Dementia is neurological disorder and a broad term used to describe a group of symptoms associated with memory loss and loss of other skills. Alzheimer’s disease accounts for 60-80 percent of all dementia cases. Last spring, I took cellular and molecular biology and one of our assignments was writing an experimental proposal, and I decided to write my proposal on the pathogenesis of AD. Currently, the pathogenesis of AD is not completely understood. However, there are few hypotheses about what causes AD. The most popular hypotheses are that AD is caused by excess production and the aggregation of β-amyloid, an imbalance in sphingolipid metabolism, or malfunctioning mitochondria. Many know that AD is associated with β-amyloid plaque buildup, however, there is another protein that is closely associated; hyperphosphorylated tau protein. Tau proteins are abundant in the nervous system as they support microtubule integrity. However, when they are hyperphosphorylated and the no longer function properly and can’t provide stability to microtubules properly. There is much to learn about Alzheimer’s disease.

            The brain is just a large, soft mass of tissue. So, most people think that people will die for a brain injury. amazingly it can handle quite a bit; for example, Phineas P. Gage. I first heard about Phineas P. Gage in a high school class, and I thought it was so crazy that someone could survive an accident like that. I’ve heard about this incident many times over during my time at college, and I still find it fascinating. I mean it’s crazy that the rail when completely through his brain, his personality basically did a 180, and yet he was able to make a complete physical recovery. He sure was lucky that he was able to survive that accident at all.

            It’s crazy that the brain can be so resilient. There have been many cases where, patients experience a traumatic brain injury (TBI) may end up forgetting to walk, but they are able to relearn. And in other cases, patients experience a TBI and are never the same again. Which brings up an interesting point; no two brain injuries are alike. Two people may experience that exact same TBI, but their symptoms and recovery may be completely different. This is probably why many brain surgeries occur while the patient is awake. I know the main reason is to ensure the surgeon affect the brain in a negative way, but maybe it’s also because there a difference in the way each person’s brain is “wired”. I mean, many surgeries are standardized, and the process is nearly the same from operation to operation. But since the brain is mysterious and unpredictable the process may vary a bit between surgeries, so they must keep the patients awake.

Microorganisms

            When most people think about microorganism a negative image pops up and they think about the “bad” bacteria that cause disease in other organisms. However, all animal and plants have established symbiotic relationships with different microorganisms. For example, our gut is home to many microorganisms that help digest our food. However, even "good" bacteria can cause us harm if they are in the wrong location or are out of balance.

            During the first few days of life, there is a period of bacterial colonization, where a sterile organism is inhabited by microorganisms that are likely to stay for the rest of there lives. So, it’s natural that these bacteria would play an important role in the development of the immune system, digestion, and absorption, and act at a barrier against pathogens. In an interesting experiment conducted by Nobuyuki Sudo, they hypothesized that the connection between microbial colonization and the immune system during early life might alter the responsiveness to hypothalamic pituitary-adrenal (HPA). HPA is a neuroendocrine system that is heavily influenced by early life. Results of this experiment showed that ACTH and corticosterone elevation in response to stress was significantly higher in germ free mice than mice with normal microbiota. The germ-free mice also showed decreased neurotrophic factors expression level compared to the mice with normal microbiota. The result of this study supports other evidence that shows communication between the brain and the gut, and that events that occur in the gastrointestinal tract have long lasting effects on response to stress. Interestingly, there is also evidence that stress can lead to change in gastrointestinal motility and that changes in gastrointestinal function affects the brain. Understanding the delicate balance between the body and brain can be important to developing new treatments for both gastrointestinal and mental disease. If specific changes in the gastrointestinal tract or brain can be connected to imbalances in the other system, we can treat the disease by correcting the imbalance.

Gene Therapy

            In class, we discussed the ethical and social concerns surrounding gene therapy. I’m currently taking biomedical ethics and one of the interesting things I’ve noticed during our discussions, is the impact that large government has on science and vice versa. Like the HUGO International, the equivalent of the U.N. for the human genome. Their goal is to bring the benefits of genomic sciences to humanity by protein genomic research, exchange of scientific information, and ethical discussions. Although it’s great that there is an international committee that is devoted to ensuring ethical genomic research, the issue is that there are no ensuring countries conducting gene therapy research are done in an ethical manner and the committee only addressed somatic gene therapy. Another interesting example of the relationship between government and science we talked about in class is the legislation created because of genetics, like the Genetic Information Nondiscrimination Act (GINA) which prohibits health insurers and employers from discriminating based on genetic information. I feel like it’s kind of weird that we have legislation like GINA to prevent discrimination genetics, but we don’t have the same kind of legislation to protect patients with preexisting conditions. I mean we could easily thing of a person’s genetics a preexisting condition since genetics play a large role in the development of certain diseases and disorders.

            Gene therapy is still being researched, many are concerned about whether changing the human germline is okay. To begin the discussion of gene therapy it’s important to distinguish between ethics and morality. Ethics objectively prescribe a standard of conduct, while morality is a system that establishing rules that relates to right and wrong. While morality may change between people and culture, ethics is more universal. So, to have a proper conversation it’s important to just talk about the ethics of gene therapy. The paper we read this week was a thesis that argued that gene editing is ethical, which I agree with as long as the proper restrictions and legislations are created to ensure the proper use of the procedure. But what I found interesting about the paper is that Austen Yeager assumed that CRISPR and gene modification carried little risk and was safe to use in humans. He had to make this assumption to be able to discuss the ethics of gene therapy, but I think it’s also important to address the fact CRISPR is relatively new technology. There are still many aspects of gene therapy that need to be refined. Also, scientist don’t know the long-term effects of gene modification. For example, scientists is just starting to understand epigenetics and the mechanism involved. There’s a lot of research that still needs to be done before gene therapy become a viable treatment for genetic conditions. So, I think right now its more important to make sure the research going into CRISPR and human genome editing is ethical. Because I don’t believe that “the end justifies the means”.

Ayurveda

            As science and medicine continue to research the unknown and gather new information about our overall standard of life and health will likely increase. And as more research is conducted, we will see knew connections and how seemingly unrelated processes are connected. By better understanding who our body, mind, and spirit are connect to other processes medical professional will learn how to better address disease and mental disorders. For example, our mental health can be greatly affected by our spiritual and physical health; like recovering from a brain injury or Alzheimer’s disease. Our brain is also affected by microorganisms, which also are important to our immune and digestive systems. And gene therapy will hopefully become another tool for treating chronic and debilitating genetic diseases. However, before gene therapy become a viable tool, we have to understand how our environment effects epigenetics and the role our genes play in our personality/mental state. Life is a balance act and so is our health and medicine.