From J. Jean Cui, a co-inventor of Xalkori in an interview in an Elsevier R&D publication:
...What is the role of the medicinal chemist in the development of precision medicine and how can younger generations prepare to make contributions in this area of research and development?
[snip]
...The adjective “medicinal” already alludes to the complexity of the work and, consequently, the demands on a medicinal chemist. He or she must understand biology, must be a data scientist, must be familiar with the full spectrum of assays and analyses that inform his or her design work. A medicinal chemist must remain up to date on developments, always look for new potential targets, new applications for a candidate drug and new ways of designing molecules to meet often contradictory requirements.
Looking into the future, as more discovery and optimization work is conducted at smaller biotech companies, the medicinal chemist will also be expected to control development costs, to seek new resources, and to interact collaboratively with a growing number of stakeholders that can inform his or her work. Though perhaps a daunting prospect, this increased responsibility will be accompanied by a greater and more direct impact of his or her work on the well-being of patients.
For a future career in medicinal chemistry, nothing can replace knowledge acquired through experience. Academic training is only the beginning of the medicinal chemist’s preparation. He or she must continue to learn from the work of designing and optimizing a compound, from the often overwhelming information that he or she must integrate, and from the people with whom he or she interacts. Important to remember is that this chosen profession is at times very frustrating, but also has moments where you advance in solving a problem and that satisfaction is unmatchable. Be always flexible and creative, and strive to do something different.One thing that Dr. Cui mentions here is the centrality of the medicinal chemist in a drug discovery project. Derek Lowe mentions this every once in a while when he says that "You are in real trouble if someone knows more about your project than you do." I think about that a lot.
[I do also have to note (whenever anyone talks about this, as Dr. Cui does here) that as medicinal chemistry moves to smaller companies, this comes with lower wages and benefits (combined the lottery ticket of an eventual buyout.)]
I worked with Jean Cui, she was a project manager on my project. She has been pretty shameless in hogging credit for work done by others. I have seen her sharp elbows and her real chemistry/management skills up close. She published my work - on the series which I designed - without my name on the paper. Eventually she wrote erratum "about five co-authors inadvertently left of the paper"...
ReplyDeleteI don't think she should be taking full credit for crizotinib, as much as she likes to. The drug has been developed by a fairly large team, for c-Met kinase - a different target, and it was quite nonselective (off-target activites). Pfizer eventually shelved the cMet project. Some times later, ALK project prompted re-screening of old compounds, crizotininb was highly potent in ALK as well, so they took it without further structural modification and used it as ALK drug; the off target c-Met activity was probably a bonus.
Sigh, this is just making me to and fro. I really can't figure whether or not it is a good idea to continue with postgraduate studies in chemistry, especially into medicinal chemistry. To quote Jean Cui directly "He or she [the chemist] must understand biology, must be a data scientist, must be familiar with the full spectrum of assays and analyses that inform his or her design work. A medicinal chemist must remain up to date on developments, always look for new potential targets, new applications for a candidate drug and new ways of designing molecules to meet often contradictory requirements."
ReplyDeleteI couldn't have personally professed my own interests or desire for my career any better - it's everything I've ever wanted to do I suppose. I am just so scared from reading this blog about the job market and prospects for PhD chemists that I've been so offput, why not just go and study something clinical like Medicine and have a guaranteed job at the end of it.
It's all a big mysterious gamble, isn't it? It is my belief that it is better to be forewarned about the worst case scenario than not. What I think Dr. Cui demonstrates here is the best case scenario - the things you get to do, should you get a position as a medicinal chemist in pharma.
DeleteKnowing the challenges you will have to face (short version: doing good work in graduate school and postdoc, finding a top-notch chemistry program to be a part of) may help you make your own cost/benefit analysis.
The problem is that the kind of people who land on their feet after every re-organization or layoff, the chemists who become successful tend to be less than impressive as scientists, managers, and human beings.
DeleteAfter SUGEN-Pharmacia, I worked directly for a chemist who was a terrible ass-kisser, terrible organizer and could not care less for chemistry done in her lab. She set us all for a failure in order to make herself look better with the top management, because she hoped to get a position of medicinal chemistry boss (the Director of medicinal chemistry had serious heart disease and was to retire). So our boss was quite ruthless - volunteering us for what else we could do (so I ended up working at the same time on scaleup, methodology development, late-stage medicinal chemistry optimization, salt form selection and doing the stability studies. We had five formulation people in a brand new lab doing absolutely nothing, so I had to do their job too. Then we found out the final compound to be scaled up cannot be purified on silica or by crystallization, so we had to purify 40g of material for rat studies by doing manual injection using semiprep column, 200mg per injection, every 50 minutes, because our boss did not want to spend money on prep HPLC. We were taking night shifts, and she was coming back with more stuff to do... ) Anyway, two jobs and promotions later, she is in charge of the entire small molecule medicinal chemistry program at a major company, with 300 people working for her. I would not let her synthesize methyl benzoate.