28 April 2014
The primary focus of the last five years of my life has been the pursuit of a PhD, culminating with my PhD dissertation and defense. A week ago I defended my PhD and was awarded a Doctor of Philosophy in Biomedical Sciences, more colloquially known as a “PhD” or “doctor of science.” I’ve decided to coalesce some thoughts and impressions into something resembling a narrative on the process.
Images: On April Fools’ Day, three weeks before my PhD defense, I sent my good friend Eric Murphy an email: “Hey Eric, I’ve attended a few PhD defenses, but I’m still at a loss whether this would be proper attire?” and included a link to the image below. His response was short: “I’m doing it.” Being April Fools’ Day, the mischievous ambiguity of his response made me unsure whether he was actually planning something. Following the vein of mischievous ambiguity, I opted to not ask him to clarify, and he showed up to my PhD defense with, yes, a D Fence. Friends and family in attendance signed the D Fence after the talk.
The dissertation is a written document describing any and all of my even remotely meaningful work from my PhD. It included some published work, and some work that has not yet been published. I wish I could go into detail about the work I’ve spent several years of my life performing, but some of it needs to go through peer review before I can open it up to the world. C’est la vie.
To complete a PhD, one must host a defense, or public lecture followed by questions by curious specialist and non-specialist minds alike. The public lecture is the first formal occasion for a new doctor to open up their research, ideas and insights to society, to be pondered and questioned by anyone.
More practically, a PhD defense is the final meeting between the PhD candidate and their thesis committee. The main difference from previous meetings is that the public is invited to attend and interrogate the logic, reasoning, research, and knowledge of the PhD Candidate. The public lecture must make something highly esoteric understandable to curious non-specialist minds. But, the talk must remain technical enough to satisfy the Thesis Committee as well. It’s also a rare chance for a PhD Candidate to display their work to friends and family, and making a presentation that can meet all of these demographics is no easy task.
I have many friends and family in the area, many of whom I’ve had to somewhat neglect in my long hours (years?) pursuing new knowledge through research. It’s entirely possible for a PhD candidate to have very few people attend their defense, but where’s the fun in that? I had given many scientific talks to scientists, but rarely to the audience I was expecting. I saw it as a tremendous opportunity to practice my presentation skills, and perhaps have some fun in the process. I’m not referring to a hedonistic, lost-in-the-moment type of enjoyment, but the rare, fleeting satisfaction of doing something well, wrought by blood, sweat and tears.
After all, my original reasons for pursuing medical research were because I wanted to learn to wield the tools of science to have a shot at making a small contribution to medicine. Medicine is a physical manifestation of humanity’s will to live longer and more free of physical ailments and pain. The last century has seen a significant maturation of the relationship between medicine and science, the process by which we reproducibly uncover and define the way the world works. In tandem we can do incredible things like cure infections, eradicate communicable diseases, and make a dent in perhaps the most difficult of diseases to treat: cancer.
Image: Dated to 2600 BCE, the Edwin Smith Papyrus is an ancient Egyptian combination of surgical trauma manual with recommended therapies for fractures, dislocations, lacerations, infections, etc. Among the nearly 50 cases are two describing cancer, for which there was no recommended therapy. The ancient Egyptians clearly recognized cancer as a very difficult disease to treat, perhaps also recognizing the futility of trying to treat it with their medical tools at the time; that intervention was worse than leaving patients to slowly perish. Image courtesy U.S. National Institutes of Health
Along this theme, I dedicated the first chapter of my dissertation to the history of cancer metastatic theory from ancient times until the 20th Century: from fossilized clues about cancer metastasis to the 4700 year old written case studies on cancer patients, to Hippocrates, Galen, Paget, Halstead, and Fisher. At some point in the future I hope to be able to reproduce (with permission) this chapter of my dissertation here on my blog.
I opened my defense talk with a short historical context on cancer, stressing that ancient societies clearly recognized cancer as a very difficult disease to treat. Hippocrates is credited with coining the term “cancer” because he likely recognized the ability of it to crawl throughout a cancer patient, or the physical appearance of autopsied tumors reminded him of a crab. He is also credited with the term “Metastasis” which translates loosely to “dislodgment” or “to be set free.”
For visceral effect, I also included a PET scan of an advanced stage cancer patient (to the right, courtesy uchicago.radiology.edu) with metastatic tumors throughout the body. I then asked my audience to imagine being a surgeon tasked with removing the tumors with a scalpel, stressing the difficulty in treating advanced disease, and how imperative it is for us to understand the process by which this happens so we may target it in means more precise than, well, a surgeon’s scalpel.
I really wish I could go into details about my talk from this point out, but as I mentioned before some of the data has not yet been published, and even more is not yet available via open access (i.e. the publications are owned by entities that charge a fee to the public to view). A discussion on the merits and pitfalls of the antiquated publication model and its (mal?)adaption to 21st century medical research is warranted, but perhaps not here right now.
The abbreviated version of the rest of my talk: Cells have mechanisms that allow for recognition of their physical surroundings and biological zip codes in the body. The means by which they interpret these signals and decide to commit cell suicide or to migrate and grow are integral to the behavior of cancer cells, and at the center of this is my favorite protein: Caspase-8. Through rigorous experimentation employing recombinant protein biochemistry, cell culture models and experiments in vivo, I demonstrated how this protein can play a dual role in cancer malignancy. My research model suggests that this behavior might be toggled by combining two yet-to-be-tested-together classes of drugs that are currently in the clinic and in late phases of clinical development.
Image: A slide from my talk, introducing the concept of metastasis as a multi-step process with hurdles for a cancer cell at every step using very crude illustrations.
Cancer is actually a group of many heterogeneous diseases with overlapping etiology and behavior. My research alone is a far cry from a “cure.” Medical research is the combined efforts of thousands (millions?) of scientists past and present, and my work builds heavily upon work performed by those that came before me. It’s a tremendous honor and privilege to take part in this tradition. By communicating my results and ideas, I am closing a small piece of that loop and contributing (a very small part) to this process.
On a personal side, perhaps the most important and practical thing I have learned in the process is that, after five years of blood sweat and tears (and a healthy helping of head banging) I want some more. I have tested the depths of my motivations and I have found that I am indeed very deeply passionate about using science to improve the physical well-being of cancer patients. There are many times where I could have thrown in the towel, but at every hurdle and hill in my way I found motivation to continue. I remain easily excited by new prospects and developments in science as they pertain to oncology, and when I grab my morning coffee I often get distracted by reading scientific papers and oncology clinical trials results.
In terms of my career, I am allowing myself to be guided by the onus of finding the most impactful, efficient way to improve cancer diagnosis, risk assessment, and therapy. I am currently exploring several options in academia and the biotech industry toward these ends.
If you’ve made it this far I thank you, dear reader.