The STING of Colonization

by Sylvia Klein

Abstract 

I enter the lab and don my small black nitrile gloves and papery, disposable lab coat. I look around at the sterility of the lab as I begin to gather the things I need for the experiment I’m planning to do. As I grab items I need from shelves, the freezer and fridge I think about how everything I am holding is plastic and will be thrown away. I try to remind myself that I am working towards having a better understanding of dengue virus to aid the over 50% of the global population that is affected by the mosquito borne disease. I think about how far removed the work is from that of the many people working in the field, often in communities lacking access to protective measures like mosquito nets. While laboratory research is vital to controlling or eradicating an infectious disease, research and public health have a dark history rooted in colonization. As researchers, we must be aware of the social context our research subject exists in and how to ethically perform the research.

Keywords: decolonization, infectious disease, equity, research

Introduction 

What is Decolonization? 

The field of public health is a direct descendant of these efforts to protect colonial power. Increased international trade, beginning in the 16th century, led endemic infectious diseases to pose a significant economic threat to the colonial empires. It became vital for colonial empires to understand the diseases their people were being exposed to. While these diseases also negatively impacted the Indigenous people of these lands, the goal of research was almost always to protect the financial interests of the colonial empire, often against the interests of native inhabitants¹. The colonies gained political health infrastructure to protect the interests of their colonial ruler. During the 20th century, independence from colonial powers led to the removal of colonial health care systems². Today many previously colonized nations continue to struggle to expand their health systems³, ⁴. The effort to increase equity and justice to these disadvantaged countries has taken on the term “decolonization”². True decolonization would require completely dismantling and rebuilding our global public health system and infrastructure. While not something an individual can feasibly achieve, incorporating the principles of equity and justice into current biomedical research is vital for reparations and a better future.

Methods 

Research Funding

From the standpoint of a researcher, understanding a disease is the best way to fight a disease. However, doing research can be extremely expensive, which negatively impacts less economically advantaged countries, many of which were colonized in the past. In developing countries, the resources for research are not available. Many of these countries are plagued by neglected tropical diseases (NTD), a group of over twenty diseases that are underfunded, understudied and undertreated. In the United States, funding for NTD has increased over the past few decades from $15 million annually, to $100 million⁶. However, this pales in comparison to the $5 billion in federal funding to study SARS-CoV-2 alone⁷. Lack of funding, leads to lack of research and publications. For example, in the biomedical research database, PubMed, a search for “SARS-CoV-2” returns 192,885 results and a search for “dengue virus”, a NTD, returns 18,011 results. Reduced funding and published research inhibits progress vital to eradicating NTD. These discrepancies in funding are a direct result of colonization as even today, diseases that impact those in control the most, receive the most resources. 

The effort to increase equity and justice to these disadvantaged countries has taken on the term “decolonization”²

Results 

A Case Study

While ethics in medicine has come a long way from Spanish soldiers knowingly giving Native Americans small-pox ridden blankets, there unfortunately still many examples of the downstream effects of colonization⁸. A prime example is the 2018 dengue vaccine trial controversy in the Philippines, a Southeast Asian country that was previously colonized by Spain, the United States and Japan before gaining independence in 1946. The Philippines is severely affected by the mosquito borne virus, dengue virus. Dengue virus has four serotypes (genetically similar, differences immunologically). Secondary infection by an alternate serotype is more likely to produce the more severe form of the disease, severe dengue hemorrhagic fever, a phenomenon known as antibody dependent enhancement. The dangerous relationship between antibody dependent enhancement and severe dengue hemorrhagic fever became even more apparent during the dengue vaccine trial in the Philippines. 

There is no widely used vaccine or treatment for dengue virus. However, the pharmaceutical company Sanofi-Pasteur has developed a vaccine, Dengvaxia. In 2017, a vaccination program was initiated in schools in the Philippines, where over 800,000 children received at least one dose of the vaccine⁹. After the initiation of the program, Sanofi relabeled the vaccine so that it was only recommended to individuals who had previously had dengue virus. The public was outraged that this had not been previously studied. The vaccination campaign was potentially involved in the deaths of multiple children, leading the Philippines Public Attorney Office to file a lawsuit against government officials and Sanofi¹⁰, ¹¹. 

The grosse mishandling of this situation has led to vaccine hesitancy and lack of trust in government health officials by citizens. Perhaps a decolonized approach to vaccine research and study implementation may have lessened these disastrous effects. This controversy serves as a robust example that better public health practices require equity and diversity. 

My Research: A Case Study

As a second year virology graduate student, sitting at a biosafety hood, there is not much I alone can do to combat the systemic colonialism in research. However, I can strive to do my best to make my own scientific interaction and research equitable and just. 

My research revolves around understanding differences in the immune response to dengue virus infection between mice and humans. The immune response is complex and dynamic, so my work focuses on a small part of the puzzle. Typically, when we are infected by a pathogen, proteins in the cell detect DNA that doesn’t belong and initiate many pathways that work to defend the host. I study the interaction between dengue and one specific pathway that involves a protein called STING (stimulator of interferon genes). Normally, when STING is activated, it leads to the activation of more proteins and leads to the generation of Type I interferon, a small protein. These small molecules then go on and activate many other pathways that are antiviral, working to control infection.

In humans, upon dengue infection, a part of the virus cleaves a protein called STING (stimulator of interferon genes). This cleavage of STING by dengue “breaks” the pathway I mentioned earlier, so the important antiviral genes that defend against infection aren’t activated. This means the virus can continue to infect more and more cells, leading to more severe disease and higher levels of virus in our cells. This interaction is relatively unique to humans and a few other mammals.

None of our model animals in research have the same interaction. Animal models are essential for developing effective therapeutics and vaccines. Dengue virus is poorly modeled in current mouse models. While there are non-human primate models, there are ethical and financial problems that make these models intractable for researchers in less advantaged countries. During dengue infection, in our models, the antiviral genes are activated – which doesn’t occur in humans. This makes comparisons between humans and model animals difficult and less useful as the response systems are different.

My work is specifically focused on understanding why these differences occur. In my work I ask if it is possible to manipulate mouse STING so that it interacts with dengue the same way that human STING does, and hopefully generate a more realistic model. So far, I have done some experiments that suggest changing part of the sequence of mouse STING may be a viable method to generate a better model. To test this, I am using the gene-editing technology – CRISPR, to edit the STING of mouse cells. I will then infect them with dengue to see if the change impacts the ability of the virus to infect cells.

Discussion 

Much of the time I spend doing research is spent at a biological safety hood, allowing lots of time for introspection on my role in science, public health and academia. In my research, I am aiming to study the molecular mechanisms that underlie why there are not good animal models for dengue, in the hopes that I will be able to assist in the generation of an animal model that is more relevant and equitable. I aim to be a part of efforts to continue to decolonize public health, through public health advocacy and equity work. In addition, I hope to improve how scientists, as a whole, view working with communities that are impacted by neglected tropical diseases and how they go about studying the diseases themselves. I hope by bringing awareness to the systemic issues within research and by trying to generate resources and make them more available to the scientific community, I may be able to play a role in increasing equity in biomedical research.

In science, research is often split into two categories: basic and translational. Basic research is research with the goal to more fully understand some biological phenomenon. Translational research is research that can be directly translated into medical interventions. My work toes the line of these two categories. The work I am doing doesn’t necessarily have a direct clinical application, but is moving the field towards a treatment for this neglected tropical disease in the hopes to mitigate some of the downstream effects of colonization.  

Often, we scientists use the real-life implication of our work in introductions to papers and grants, but that purpose is mostly used for justifying the work to whomever is providing the funding for the research. In a similar thread, we accept Eurocentric scientific ideology, such as the idea that negative effects to people and the environment are the cost of better future medicine. The pile of plastic I end up with at the end of the day sometimes makes me wonder if the outcomes we strive for are worth these costs. There is a disconnection between the sterility of science and the people we aim to help. 

Plastic use has come to be a symbol of these trade offs for me. The range of mosquitoes is beginning to widen, resulting in even more people being at risk for diseases such as dengue. The range is expanding as a result of rising global temperatures. Reducing plastic consumption has become a goal of many people and communities, but reducing plastic use in laboratories is difficult as it is embedded in how things are done and often can not be recycled due to biohazard concerns. For me, plastic ties the cost of research to the near future reality where mosquito borne-viruses will begin to impact countries that were once colonial powers. 

A decolonized approach to research is advantageous to all global citizens. Many people in power are currently unaffected by neglected tropical diseases, but expanding mosquito ranges will change this. Increased funding and resources for neglected tropical diseases will be immediately beneficial for many previously colonized nations, but in the long term will be beneficial for all of humanity. 

References