As I contemplated the contents of this essay I realized my interest in medicinal chemistry actually started 40 years ago when I was in high school. My initial forays into this field included an ill-fated attempt to prepare the local anesthetic ethyl chloride in my parents’ garage. I am not really sure they completely understood what I was doing. The place must have smelled like a distillery since the first step of the synthesis was the production of ethanol by yeast. How I expected to isolate the ethylene gas required as the reactive intermediate in my planned synthesis is a mystery to this day. Suffice it to say, my project was put on hold when I found that I could only purchase concentrated sulfuric acid in tanker car volumes.
Ironically, my initial career goals were to be a Spanish-speaking lawyer in New York. However, my 10th grade schedule wouldn’t allow for Spanish I, so I took chemistry instead. The rest, as they say, is history. I also built a gas chromatograph in high school and carried a slide rule on my belt…so I didn’t have many friends. I never studied Spanish or law. So much for childhood dreams, but I think things have turned out pretty well.
I am now proud to say that the experience garnered in these rougher years and the intervening four decades has finally paid off! I believe I now possess a rare combination of “academic” enthusiasm and medicinal chemist cynicism that makes me perfectly fit for my work in the ITDD (The Institute for Therapeutics Discovery and Development).
If you will pardon a dog-like metaphor, academics are typically like enthusiastically-herding border collies (this is most assuredly meant as a compliment) whilst medicinal chemists (at least the industrial types I know) are more like Dobermans with their jaws around your calf. My crossbred nature, nurtured by stints in the ivory tower (Dartmouth College) and the halls of medicine (Parke-Davis and Pfizer), turns out to be ideal for my current role as an innovation forager. In the ITDD I work at the interface of academic dreams and translational reality on a daily basis. To be ultimately effective I need to engage the dreams, seek out the truth, and then attempt to nurture the dream while injecting a dose of reality into the process. The evanescent, cloud-like ideas of great science may not be easily condensed into effective restoratives, but that’s my job…and I love it! I have had the chance to work on projects ranging from to Alzheimer’s disease and ataxias to anti-fungals and suppressors of suppressors, the latter being a new anti-tumor vaccine adjuvant discovery project. Where else would I get an opportunity like this?
My association with the Grossman Center for Memory Research and Care began back in 2007 when I met with Karen Ashe and Kathy Zahs on an interview trip in the Phillips-Wangensteen Building warren. They were both soo excited to talk with a medicinal chemist who might help decipher the interactions of Abeta56* with NMDA receptors that I left their company determined to work with them when I started my position at the UMN. While there are passionate researchers in industry, my experience is that none of them possess the passion for their work that many of the colleagues I work with in the academy. Decades of research focused on the same field is the difference, I suspect. Over the years of my collaboration with the GCMRC I have learned a bit about the biology of Alzheimer’s disease and have been able to contribute, in my own small ways, to the execution of projects related to AD drug discovery. I consider this a privilege. It is satisfying that I can apply my skills and the skills of my coworkers to such a potentially impactful project. Unfortunately, many AD biology researchers want for a translational institute like the ITDD. Their discoveries frequently languish in the valley-of-death between idea and utility because they don’t have the support needed to prepare proof-of-concept compounds. The biological and clinical expertise of the Grossman Center is a perfect match for the medicinal chemistry and other early stage drug discovery skills available at the ITDD. I am happy to be part of this match! And now I think I have plenty of friends!