Dr. Craig Lindsley


As one of the directors (co-director with Dr. Jeffrey Conn) of the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD), Dr. Craig Lindsley is part of a growing initiative at Vanderbilt to turn the university into a hybrid pharma-academia drug development powerhouse. After his post-doc at Harvard, Dr. Lindsley spent six years at Merck where he established the Technology Enabled Synthesis (TES) group. Using a parallel synthesis approach combined with microwave synthesis technology and a custom LCMS platform, Dr. Lindsey led the development of proof of concept compounds for nascent drug development programs. In 2006, he brought his talents to Nashville, TN, to direct the medicinal chemistry efforts of VCNDD.
Based on his industry achievements, patents, prolific rate of publication in high-tier journals, and awards spanning decades of work, Lindsley's name is surely one known by most scientists in the world. Still, with everything he's done and will do, that recognition should reach far beyond the confines of chemistry or neuroscience. Luckily, I found this picture, which is proof that his work rings in the ears of those who ring ears.
The following interview took place on September 16, 2016.
INTERVIEWER
Where’d you grow up?
LINDSLEY
Houston, Texas, and then a tiny town called Lufkin (setting of Friday Night Lights).
INTERVIEWER
Who and what inspired you as an early scientist?
LINDSLEY
Dave Ball, one of my professors at Chico State. He had a real passion for teaching and training students. He got me hooked on organic chemistry.
INTERVIEWER
Can you provide a brief summary of your PhD work?
LINDSLEY
My PhD was organometallic methodology and organic synthesis. I developed bi- directional, di-metallic polyene linchpins to make all E-conjugated polyenes.
INTERVIEWER
What would you say is key to the young scientist's development? To me, research science and the arts are parallel paths. Careers defined by the ability to bounce back, withstand failure and rejection (failed experiments, rejections from publishers), remain obstinate, and demand a creative approach.
LINDSLEY
I agree – focus, flexibility and intestinal fortitude – you have to be able to bounce back from failure and rejection. Science is 99% failure and rejection.
INTERVIEWER
What is something today’s graduate students should be jealous of from your graduate school experience? In what ways are you jealous of current PhD students?
LINDSLEY
The time to really delve into pure basic science with no rush to apply to translation. But I'm jealous of the technology at their disposal to be productive – they can do in a day what used to take me a week. Also, the ability to do translational science.
INTERVIEWER
You spent some time in a few different pharma positions after your post-doc at Harvard before starting at Vanderbilt in 2006. Has the notion that industry scientists don’t jump or aren’t recruited to academia, and vice versa, changed, or is that a misconception?
LINDSLEY
Twenty years ago, you chose a path out of your postdoc – either industry or academia – and there was very little opportunity to cross-over. Now, everything is different. People move back and forth between the two worlds pretty seamlessly.
INTERVIEWER
On a related note, how has the academia-industry interface changed in your career? Collaboration and “big” science have emerged as key themes in initiatives such as the Cancer Moonshot, and this relationship is integral to the pipeline of discovery to therapy.
LINDSLEY
Big-team science is emerging as a new paradigm for academia to mirror industry. The industry is engaging academics earlier and earlier, as they are charged to outsource 50-75% of all discovery. Both of these factors have been key to developing “drugs” in the academic setting. Overall, it's a very exciting time!
INTERVIEWER
What's your favorite book(s), or what was your favorite book around the age of 15? I know this is a terrible question, but I think it's an important one.
LINDSLEY
Lord of the Rings.
INTERVIEWER
Do you pay much attention to scientific journalism? Do you think science is reported effectively in this country?
LINDSLEY
The lay press almost always tells a one-sided story. Science needs a better voice in the US.
INTERVIEWER
You’re involved in drug development targeting many different diseases. From a medicinal chemists' standpoint, your approach at the molecular and atomic level is informed by the same physical and chemical laws that govern interactions and activity at that scale, but, concurrently, do you also find yourself learning a lot about the disease?
LINDSLEY
Always. Medicinal chemistry is only as good as your understanding of the target and disease. Medicinal chemists have to understand the entire project at a high level to be successful.
INTERVIEWER
At this point in your career, what accomplishment or discovery are you most proud of?
LINDSLEY
Developing the field of allosteric modulation of GPCRs and kinases.
INTERVIEWER
"Brain training" games, the spike in neuroscience PhDs, gut-brain axis. Everyone's interested in studying the brain to unlock its mysteries. As a prominent CNS researcher, what will be the big discovery in the next ten years?
LINDSLEY
I think the gut-brain axis will continue to gain relevance. The big discovery will be how to stratify and select the right patients in CNS phase II and phase III trials to increase success.
INTERVIEWER
What was or will be the biggest medicinal chemistry breakthrough of your time?
LINDSLEY
I think the cure for HCV and the ability to make HIV a treatable disease. Hopefully, we will find a cure for Alzheimers in my lifetime – that is the challenge of this generation.
INTERVIEWER
Tell me about KISS. Why KISS? When did it all begin? I was introduced to KISS with “Lick it up” and cheap beer, so I get it.
LINDSLEY
I saw KISS when I was 6 on the KISS Alive tour in 1976. It warped my fragile little mind, and I've loved them ever since (I've seen them on almost every tour). In answering, I realize I’ve listened to them for over 40 years – soon I will out live them and I do not know what I will do. Guess I need to start my KISS cloning project ASAP.
INTERVIEWER
Last, but not least: Beatles, Stones, Floyd, or Zeppelin?
LINDSLEY
Beatles – their song writing is second to none.
Learn more about Dr. Lindsley and his lab here. Also, Craig recently received the Pharmacia-ASPET Award in Experimental Therapeutics from the American Society for Pharmacology and Experimental Therapeutics (ASPET). Read about that here.
Feel free to leave your thoughts on the interview in the comments section.