John Butler

Senior Scientist, Medicinal Chemist at Amgen

Informational Interview: March 2019

Dr. John Butler is a UTSW graduate school alum from Dr. Joseph Ready's lab in the Organic Chemistry department. During his time in graduate school, Dr. Butler pioneered syntheses of kibdelone C and simaomicin alpha, two complex aromatic polyketide natural products. Evaluation of the antitumor properties of kibdelone C evolved into a highly collaborative project at UT Southwestern, involving the laboratories of Dr. Nijhawan, Dr. Rosen, and Dr. Posner.

Dr. Butler has since moved to Amgen, where he has started a successful career in medicinal chemistry. He has been involved in a variety of projects, including Amgen's recent drive to development selective inhibitors of the voltage-gated sodium (1.7) channel for the treatment of pain, and has since been the Chemistry Lead for an early-stage program for Parkinson's Disease.

What originally drew you to Organic Chemistry?

Going into college I liked science and wanted a career that would impact human health so I pursued a pre-med program. When I took chemistry I really enjoyed the classes and due to excellent teachers and the small department at the University of San Diego I was able to interact a lot with my professors who encouraged me to focus on chemistry. When I took organic chemistry I really enjoyed the problem solving and the connection to medicine. I gained exposure to synthetic chemistry and drug development at ACS conferences and through the then booming biotech industry in San Diego. I was able to participate in undergraduate research in computational and synthetic chemistry and really enjoyed working in a research lab. I've always loved building things: from Legos to working construction in high school, and decided I wanted to learn how to make molecules and specifically some of the toughest molecules: natural products. I decided to pursue graduate school in synthetic chemistry with as much interdisciplinary training as possible, this and the encouragement of Stu Ravnik, led me to the graduate program at UT Southwestern.

How did your career path evolve to a Medicinal Chemist at Amgen?

I think I always wanted to work in industry after graduate school even though there were definitely times when I thought that wasn't going to be the path for me. After a lot of training in organic synthesis I came to Amgen, as most entry level chemists come to industry, straight out of academia and without any experience with the job I was hired to do except for the basic chemistry skills required. Through on the job training and good mentors I slowly gained experience and greater understanding of medicinal chemistry. There are constantly new things to learn which is one of the great aspects of the job.

What is your average day like at Amgen?

My day to day is highly dependent on what project I am working on and what my role is on that project. Early on in my career I spent 95% of my time on synthesis and design of target analogs for my project. This involves regularly taking in the data being generated by the team in assays and trying to understand and make connections with the structure so that new targets can be designed. This make - test - design cycle is the basis for any medicinal chemistry effort. Currently I am the chemistry lead for an early stage program for Parkinson's disease. I spend most of my day analyzing data and communicating with team mates in other functional areas such as neuroscience or pharmacokinetics and drug metabolism to design experiments and queue compounds in assays to get the data needed to guide optimization of the chemical matter we are working on. I also spend time working with other chemists on the team to design analogs and trouble shoot chemistry. All of these efforts are highly collaborative and is why I really enjoy early stage drug discovery.

How is chemical synthesis in industry different from synthesis in academia? What skills have you gained?

I think for the most part when you are working on a project in an academic lab you tackle one synthetic problem at a time, setting out ideas for experiments and prioritizing them in order of probability of success. As a medicinal chemist in industry we come up with ideas for analogs that will deal with the problems of the project. The amount of time spent making a certain analog depends on how likely it will be successful, which is often difficult to predict. We need to be able to prosecute many ideas quickly and can't spend a lot of time on something if it is very speculative. This means we need to use reliable chemistry to access analogs quickly; the protein we are trying to bind doesn't care if we used the coolest new JACS method to make a compound. That being said, there are times when the data or a model point to prioritization of a specific analog that might be very difficult to synthesize and this is when coming up with creative synthetic solutions can have a huge impact. In these cases being able to make anything and having a breadth of synthetic experience are crucial.

In terms of the actual practice of synthetic chemistry, industry and academia are very similar. I think the main difference is that there are many resources for purification that are available in industry and learning how to utilize these can be a challenge. You have to be open to new ways of doing things and seeking out advice.

What translatable skills make employees successful in the pharmaceutical industry? What can graduate students do to cultivate these across a variety of departments?

Communication is a huge part of being effective in a team of scientists. Being able to communicate effectively with scientists outside your area of expertise is especially important. As a grad student, making an effort to discuss research outside your area is good practice for this. I think making time to gain exposure to research areas outside of your specialty are also a good way to not only broaden your experience but can also let you find out if you would enjoy working in a more interdisciplinary environment. Other translatable skills that are important are those that are important for being a good scientist: critical thinking skills, creativity, curiosity, and personal organization. As a student in synthetic chemistry, I can't remember having many opportunities to analyze large data sets which is very common in medicinal chemistry. Trying to discuss data with your lab mates when you can is not only helpful with this translatable skill but will probably improve everyone's research too.