All posts by Shraya Sharma

A Reflection On Our Evolutionary Medicine Class and Five Reasons as to Why Evolution is Important

For my last blog post, I thought it would be appropriate to reflect on this course and the significance of evolution in the broader context of medicine and drug development. In his Huffington Post article, Steven Newton briefly explains five reasons as to why evolution is an essential component of modern medicine. The five areas of medicine where evolution plays a critical role (in Newton’s list) are: H1N1 and emerging diseases, HIV, vaccines, antibiotic resistance, and drug development. While the notion of evolution may conjure an image of a slow process, this article demonstrates otherwise. Four of the five topics that Newton mentions emphasize how rapidly evolution can occur and how it mandates the development of new treatments, vaccines, and antibiotics.

On a deeper level, however, this article is particularly relevant to this course as many seemingly ‘obvious’ statements that Newton mentions now carry a deeper evolutionary meaning and context with them. For example, when Newton mentions how ‘rapid evolution combined with rapid travel’ can lead to the spread of a disease, I am reminded of our class discussion on how human behavior and rapid transportation have facilitated the transmission of many infectious diseases. Furthermore, Newton’s reference to how a ‘multi-drug’ approach is better suited for HIV treatment (due to the virus’ rapid evolution) reminds me of Dr. Goldberg’s lecture on cystic fibrosis (CF) and how drug cocktails have been used to treat patients with CF. The article’s discussion of the importance of vaccines and the mechanisms behind how they work serves as a reminder of Dr. Mina’s lecture on LAIVs and the common misconceptions associated with vaccines. Additionally, Newton’s discussion of how antibiotics can “[wipe] out almost all [of an individual’s] bacteria” reminds me of Justine Garcia’s lecture on the critical role that the microbiome plays in health and disease outcomes. And lastly, Newton’s reference to drug development and the use of animal models serves as a reminder of our discussion on personalized medicine and the inaccuracies associated with animal model testing. Thus, by fortifying our understanding of fundamental evolutionary principles and by providing us with a plethora of examples of how evolution shapes modern medicine, this class has equipped us with a deeper insight and appreciation for Evolutionary Medicine and its wide applicability to the past, present, and future of medicine.

http://www.huffingtonpost.com/steven-newton/five-reasons-why-evolutio_b_459636.html

Engineering Malaria-Resistant Mosquitoes

This Scientific American article delves into the genetic engineering of malaria-resistant mosquitoes in an effort to reduce malaria transmission between vectors and hosts. By injecting an engineered gene into the Anopeheles stephensi mosquitoes’ eggs, Dr. Anthony James and his colleagues were able to breed malaria-resistant mosquitoes that were incapable of transmitting the malaria parasite to humans with a bite. Intriguingly, the engineered gene has been shown to be dominant; consequently, Dr. James and his colleagues believe that releasing the malaria-resistant mosquitoes in strategic locations could potentially reduce transmission rates significantly. This novel development in the field of infectious diseases is particularly significant as many scientists predict that climate change (and increased rainfall) may increase the prevalence of malaria by providing mosquitoes with more breeding sites through puddles. One obstacle to this transmission-reducing method, however, is that researchers would have to generate millions of malaria-resistant mosquitoes and subsequently release them into specific locations at strategic times. While this novel method for reducing transmission rates does face certain obstacles, it could potentially be used to reduce the prevalence of other vector-borne diseases such as dengue fever and the West Nile virus. Consequently, Dr. James’ study has significant implications for the prevention of vector-borne diseases, particularly in areas where access to medical resources may be scarce. This Scientific American article is relevant to the nature of our malaria discussion as we briefly mentioned how scientists have genetically engineered malaria-resistant mosquitoes; as a result, it was interesting to gain a deeper understanding of how researchers have actually accomplished this.

http://www.scientificamerican.com/article/malaria-resistant-mosquitoes-lab-bred-first-time/

Cohuet 2010 Summary

The article delves into the evolutionary selection pressures that have shaped the vectorial capacity and competence of Anopheles mosquitoes. Cohuet et al. begin by addressing the impact of parasite virulence on a host’s fitness; in particular, the team narrows down the infection-induced costs to fitness to a reduction in survival or the ability to reproduce. To explain a possible reduction in longevity from Plasmodium infections, Cohuet et al. proposed four hypothesis: cell damage, a costly immune response, competition between the host and parasite for resources, and parasite-induced behavioral changes that increase mortality. Cohuet et al., however, reasoned that a reduction in fecundity is a more commonly observed fitness cost of infections as it minimally affects transmission rates in comparison to a reduction in longevity. The article also delves into the length of the sporogonic cycle as a determinant of vectorial capacity; specifically, Cohuet et al. suggest that a longer time for sporogonic development favors producing higher number of sporozoites. The group further suggests that carrying out the sporogonic cycle at an optimal temperature yields a high number of sporozoites while decreasing the length of the sporogonic cycle. Intriguingly, a study revealed that Plasmodium­-infected flies demonstrated a greater attraction to higher temperatures than non-infected flies. Additionally, Cohuet et al. present a hypothesis suggesting that anthropophilic behavior plays a role in vectorial capacity. I find this hypothesis particularly appealing as it provides an evolutionary and historical context for the adaptation of high vectorial capacity in the Anopheles species. While the article delves into many studies and biological processes, I feel that Cohuet et al. do an excellent job of emphasizing the underlying evolutionary theme throughout the article. The notion that there is a constantly evolutionary ‘race’ between parasites and their hosts is rather intriguing; in particular, the fact that this adaptations ‘race’ often leads to rapid evolution is particularly interesting as the theory of evolution generally evokes the connotation of a slow process that occurs over thousands and thousands of years.

The Human Microbiome May Be Seeded Before Birth

This NYTimes article is relevant to the nature of our discussion on microbiomes and how they can be used for the treatment of various disorders. The article begins by addressing the common misconceptions that fetuses are sterile and that babies are first exposed to bacteria when they exit the birth canal. In 2010, Dr. Josef Neu closely studied stool samples from newborns before their first meal and found diverse microbes in the samples, regardless of whether the child was born on time or prematurely. Additionally, Dr. Esther Quintana studied the amniotic fluid, placenta, and umbilical cord blood of healthy babies and found that each contained a certain amount of bacteria. Questions remain, however, on how the bacteria are first transported from the mother to the fetus and whether a random or beneficial set of microbes are delivered to the fetus during pregnancy. Currently, Dr. Neu and other researchers are studying whether a microbiome helps a fetus during pregnancy. Intriguingly, beyond exploring the microbiome found in fetuses, researchers are also closely studying how the microbiome can be functionalized to treat disorders such as gut infections and autoimmune disorders. For example, the article mentions the possibility of providing a mother with a ‘microbial cocktail’ that can be used to transport specific microbes to the fetus for the treatment of a specific disorder.

I found this article rather interesting as I was not aware that bacteria naturally occur in fetuses, amniotic fluid, and placenta blood. Building from our discussion in class, this article is evolutionarily significant as it suggests that a mother can possibly influence her child’s microbiome, which can ultimately have extensive health and dietary impacts for the child.

http://www.nytimes.com/2013/08/29/science/human-microbiome-may-be-seeded-before-birth.html

Body Parts on a Chip

Link to TED Talk:

http://new.ted.com/talks/geraldine_hamilton_body_parts_on_a_chip?utm_source=email&source=email&utm_medium=social&utm_campaign=ios-share

This TED Talk is particularly relevant to our Tuesday discussion regarding the accuracy and safety of using animal models to predict the effect(s) of a drug in humans. In this TED Talk, Dr. Geraldine Hamilton introduces a new model called Organs On A Chip. The chip recreates the basic functional units of an organ as well as the biochemical, functional, and mechanical environment normally experienced by the cells/organs in the body. For example, a recreated lung, in a nutshell, consist of a porous membrane, two fluidic channels (for blood and air flow), capillary cells, and lung cells. Additionally, the porous membrane of the lung is contracted and relaxed to mimic the mechanical strains that the lung cells experience during ventilation. To test various conditions – chemicals, bacteria, immune cells, viruses, etc can be added to the fluidic channels to monitor their interactions with the cells and one another. For example, to mimic a lung infection, bacterial cells were added to the air channel and immune cells were added to the blood channel; intriguingly, the immune cells crossed the porous membrane and phagocytosed the bacterial cells. Lastly, because Hamilton’s group has successfully recreated the liver, gut, heart, and bone marrow, these chips can be connected with fluid channels to further study the interaction of drugs/chemicals in the “Human on a Chip.”

I think Dr. Hamilton’s TED Talk is incredibly fascinating as it offers a novel, safe, and accurate model for testing drug interactions in the human body. Additionally, I believe this technology essentially carves the pathway for personalized medicine and pharmacogenomics as cells from specific individuals, populations, and age groups can be used to recreate organs. Furthermore, this model shows vast potential for studying the complex biochemical interactions between drugs and other chemicals/cells as a number of substances/cell types can be added to the fluid membranes to mimic an in vivo environment. Lastly, by simulating some of the complexities of a human body, the human on a chip shows potential for bypassing the unethical use of animal models.