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Legacies

To graduate from my PhD program I need to make a novel contribution to my field. This requirement is fulfilled by publishing a first author manuscript. Such a manuscript is a peer reviewed presentation of my work. The review process ensures that my work is novel, meaningful, and that my findings are supported by my evidence.

I began my PhD studies believing that my contribution would be revolutionary – just like those by Newton, Darwin, Einstein, and other notable scientists from history. I anticipated that I would find the mechanism for JMML development; that I’d discover the future therapy; and that clinical trials would be starting just as I was returning to medical school for MS3.

Such dreams are necessary to keep a young scientist motivated. Yet they describe the goals of a whole career, not a thesis project. In reality, scientific progress is slow and incremental. Knowledge is built upon a strong foundation and my goal as a trainee is to build for myself the most solid foundation that I am able. Now, in my third year of graduate studies, I’ve realigned the goals of my current studies to this reality.

But does this mean I have to delay making a contribution until my foundation is set? Can I make a difference now?

I believe that I can and I believe that I have. Yet, to have done so, I’ve had to redefine my measures of success. I can leave a legacy as a graduate student, but only once I recognize that such a legacy will not involve revolutions, cures, or press releases. I will describe one small contribution that I believe I’ve made and the three steps that I took to make it: i) identify a need, ii) find a solution, and iii) share my findings.

The Yoder lab is known for its work with human ECFCs: endothelial colony forming cells. These are highly proliferative cells that are currently (with no contribution from yours truly) in clinical trials for various vascular disorders. The lab uses these cells to study vessel formation. One set of experiments studies ECFC vessel formation in the context of supporting stromal cells: fibroblasts, mesenchymal cells, cancer cells, etc. However, when multiple cell types are mixed, it can be challenging to discern the contribution of each to vessel formation. A cell can morph, change shape, die, etc.

The solution: mark each cell type with a unique tag, such as a fluorescent proteins. If all ECFCs are red and supporting cells are green, then you can discern the contribution of each cell  type simply by comparing the role of red vs. green cells. Additionally, you can take striking pictures of these cellular interactions.

Yet, ECFCs do not innately express fluorescent proteins. They need to be introduced into these cells using viruses. To do so, one must first identify which type of virus can efficiently infect your cell of interest. Then, you need take this virus subtype and modify it to express the fluorescent protein. Then, this virus must be grown, introduced to the target cell (ECFCs), and hope that the virus does not cause the ECFCs to die or stop growing.

Previous researchers in the Yoder lab have infected ECFCs before, but with various efficiencies and unspecified methods. When I needed to have colourful ECFCs for one of my experiments there was no protocol for me to follow. Thus, I became to nth researcher in my lab to re-develop a system of infecting ECFCs.

I was fortunate: I had experience in other labs with viral production. I reconnected with these labs, modified their protocols, and over many iterations refined my methods until I was reproducibly able to produce viruses that could infect ECFCs with efficiencies of >98%.

GalV v VSVG tdTOM ECFCs

At this moment I stood at a fork in the road. I could rush forward with my experiment, using my efficiently colourful ECFCs for my own studies. Or I could pause my own work to write out a protocol that I could share with others. From a collaborative or distant perspective the choice is clear: share your findings. But from the grad school trenches the perceived need to rush forward with my own work was overwhelming. After all, the colourful ECFCs are not a sufficient contribution for me to graduate. Only the studies that use them could appease my Thesis Committee and allow me to obtain my degree.

I realized, however, that whichever fork I chose, my goal would be the same: to leave behind me a legacy – a piece of knowledge for others to have and use. I therefore chose to go ahead with the definite legacy: a wrote our a detailed protocol for how to design and make viruses and how to use them to infect ECFCs. This contribution cannot rival those of my science heros. Nor will it help me defend my PhD thesis in front of my Committee. However, it exemplifies the very reason that I chose to pursue a career in science: sharing my newfound knowledge with others in the hope that they will use it for their own purposes.

Protocol

The views expressed in this content represent the perspective and opinions of the author and may or may not represent the position of Indiana University School of Medicine.
Author

Stefan Tarnawsky

MS4 MD/PhD Student. Going into Internal Medicine; interested in Heme/Onc. Bread baker, bonsai artist, aspiring astronomer.