Lost in Translation

I hope to return to the lab after this year and try to understand why immunotherapy is lifesaving for some patients like President Carter, while others like Mrs. B remain lost in a biological dark matter. Above all else, I am drawn to the opportunity to fight in her corner once more.
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She was dying.

Diagnosed with invasive colon cancer at age 41 and having undergone many unsuccessful interventions, Mrs. B, a police dispatcher and mother of two, came to us with hopes that an experimental therapy might find her cancer's Achilles' heel.

I was 23. I had just finished my first year of medical school and landed a summer gig on a clinical trials team at a prestigious cancer center. My previous research occurred entirely in the laboratory, where cancer existed only through the lens of a microscope or the label "Ca" on a test tube. But now, cancer had a face. If she met all of the criteria, Mrs. B would be the 11th and final person enrolled on this arm of the trial before it closed.

Prior to meeting Mrs. B, I had spent months studying the pathogenesis of disease during the first year of medical school. The clinical encounters that I had were focused on eliciting a proper medical history and being able to interpret and articulate a patient's narrative. All of this made me a good fit for the summer job on the clinical research team. Cancer patients who had exhausted other treatment options would reach out to us, inquiring about joining the investigational protocol. When their paperwork and tissue specimens arrived in the mail, I would review their records, helping my boss evaluate if they met the trial's parameters. A trip down to the pathology lab would allow me to analyze their biopsy samples for over-expression of a protein called HER2/neu, the unifying target shared by all our brave participants.

This trial was designed to test a therapeutic vaccine. It is a member of a broad new modality in cancer treatment called immunotherapy- medicines that are designed to turn the powers of the immune system against cancer. 2015 was a watershed year for cancer immunotherapy, with several new agents for the treatment of melanoma, lung and kidney cancers and multiple myeloma approved by the FDA. Recently, President Jimmy Carter announced that he has recovered from stage IV melanoma that had spread to his brain, thanks to treatment with one of these powerful, new agents.

The emergence of immunotherapy into clinical practice represents the success of translational research, in other words, conducting basic scientific inquiry and using the resulting knowledge as a scaffold on which to build new medicines. By studying the fundamentals of life, we can understand what goes wrong in disease and develop targeted interventions. It takes science from the lab bench to the bedside.

But this exciting progress is sadly occurring within an unpredictable research landscape. The 2016 federal budget and the "Moonshot for Cancer" announced in President Obama's final State of the Union promise a boost in funding for biomedical research. While encouraging, the new support comes after 12 years of flat funding and illustrates the volatile climate of modern science in the US. The sequestration cuts of 2013 dealt a major blow to our community. A report from that year entitled Unlimited Potential, Vanishing Opportunity published by the American Society for Biochemistry and Molecular Biology found that 18% of American scientists are considering taking their work to another country. Additionally, with more researchers competing for limited grant money and the tuition of medical school continually rising, bright young students are foregoing careers in science and medicine altogether.

These factors weigh heavy on my mind. I love conducting research and had always planned to pursue a career as a clinical investigator. But where is the sense in chasing a future that relies on the ability of Congress to produce stable budgets? Why not get a job in private practice where a higher salary would allow for easier repayment of my substantial student debt? Many scientists now often talk about a "great paradox;" the reality that biomedical research has never been better positioned to deliver transformative breakthroughs, yet the resources needed to produce those discoveries are plagued with great uncertainty.

On the day that Mrs. B was asked to come in for a screening physical -- the final step before being invited to join the trial -- I planned to wait for her in the lobby. The large research hospital can be daunting and I enjoyed greeting our prospective patients at the door. Off in the distance I spotted a frail woman and her husband. Though I had no idea what Mrs. B looked like, after hearing her voice on the phone so many times, it just had to be her. I waved but they had turned and were heading in the wrong direction. I reached into my pocket and dialed her cell number from memory.

After her clinical evaluation, my boss agreed that she was a great fit. Mrs. B and her husband wept as she signed the trial's enrollment paperwork. There was hope once more.

That night, I packed up my car. My summer fellowship had ended and it was time to head back to Buffalo for my second year of school. I returned to my bedroom to find a voicemail left on my phone. It was from Mrs. B. She called to thank me for helping her navigate down this new path. "I was lost in translation, but you fought in my corner," she said. I never deleted the message.

Mrs. B died last spring at age 43. She responded poorly to the vaccine and her disease further metastasized. After hearing the news, I pulled out my phone and listened to her voicemail again. The optimism in her tone was palpable. Her voice instilled in me a renewed sense of conviction. I recently applied to a competitive fellowship program that provides research-oriented medical students the opportunity to temporarily pause medical school and spend a year working with world-renowned scientists and clinicians.

Ironically, while she credited me with helping her find the way, it was Mrs. B that revitalized my passion at a time when I was feeling cynical about the road ahead. I hope to return to the lab after this year and try to understand why immunotherapy is lifesaving for some patients like President Carter, while others like Mrs. B remain lost in a biological dark matter. Above all else, I am drawn to the opportunity to fight in her corner once more.