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PROFILE: Antisense pioneer Stanley Crooke on injustice, the American dream, and letting go

This article was originally published in Scrip

Executive Summary

Dr Stanley T Crooke is founder, chairman and CEO of Isis Pharmaceuticals. He has led the R&D of more than 20 marketed drugs and the scientific development of a whole new platform for drug discovery: antisense technology.

Dr Crooke's early career was spent at Bristol-Myers Squibb, where he created the first broad anticancer program in history, and later at SmithKline Beecham, where he was responsible for worldwide R&D. About 25 years ago he founded Isis, where he conceived and implemented the scientific and business strategies that led to the invention of antisense, and brought to market the first two drugs based on this this platform technology: Vitravene (fomivirsen) and, more recently, Kynamro (mipomersen).

In the latest instalment of Scrip's executive profile series, Dr Crooke talks of the tough early experiences that formed his values, the impact that a good mentor can have, and his surprising ability to relinquish control.

Dr Stanley T Crooke

Scrip: You have risen to a leadership position in your field. What has been the secret to your success?

Stanley Crooke: Training, commitment, energy, perseverance, leadership skills. Without having planned it, it turns out I'm uniquely well-trained to do what I do today. I am an MD, PhD, trained in molecular pharmacology and in RNA biochemistry. I was lucky early in my career to be given senior leadership positions in drug discovery and development. Thus, I know pharmacology and medicine, drug discovery and development and the RNA world. I am committed to the patients and science and understood when I founded Isis that doing what I planned would require perseverance from me and my colleagues. Even today, I never get tired while I work and doing everything necessary is rarely a problem. Finally I think I am a good leader and a manager.

Scrip: What are your own long-term aspirations?

SC: To create a novel, more efficient drug discovery platform that changes biological sciences, that results in drugs that improve the lives of patients with many diseases, that supports the creation of a unique "fully disintegrated pharmaceutical company" and returns great value to our shareholders. We are not quite there yet, but I think all of our hopes are within our grasp.

Scrip: What are the key things that shaped you when growing up?

SC: Anger and desperation. Anger at the unfairness I saw and experienced; desperation to have something more to life than what I saw around me. Although there are many, I'm sure, who come from more difficult environment, I have known what it means not to have a bed or enough to eat. Being the first person in my family to graduate from high school and being on my own with no guidance, I had to create myself. I made mistakes and had false starts, but the unfairness that I experienced and the desires to be fair and be fairly treated were central to my life. Finally, the desperation came from knowing that I couldn't be a mechanic meant I had to find something else to do.

Scrip: Who was your biggest influence, and why?

SC: The late Dr Harris Busch, former chairman of pharmacology at Baylor College of Medicine. Harris was instrumental in my being admitted to Baylor Medical School. (I still don't know what he saw in me, as it was certainly not my undergraduate grades.) He introduced me to medicine, science and intellectual life, and taught me to demand more of myself and others. He and his wife Rose were the closest thing to parents and a family I have experienced.

Scrip: What is the best advice you've ever had?

SC: Find what you love to do and do it. I think this is the advice that I give based on my own experience.

Scrip: Who do you admire in the industry, and why?

SC: I particularly admire the financial leaders like Fred Frank and Stelios Papadopoulos who helped create the biotechnology industry. I admire R&D leaders who remain great scientists while they have large administrative burdens such as Karl Beyer from Merck long ago. I also admire ground-breaking scientists like Sir James Black [the late Nobel prizewinning physician and pharmacologist].

Scrip: How do you step back and get perspective?

SC: It's hard as we are all trapped in the day-to-day, but I try to encourage myself and others to celebrate successes and be active learners when we experience disappointments.

Scrip: And how do you relax?

SC: I am relaxed most of the time, but I hike, play chess, read novels and American history, and watch sports.

Scrip: Tell us something surprising about you.

SC: I very easily give up control of most things in my life. I only need to control very few things.

Scrip: If you weren't a pharma executive, what would you be?

SC: An academic scientist/physician.

Scrip: What has been your proudest moment? And your most difficult?

SC: I have not had my proudest moment yet. There have been two times when Isis suffered disappointments and I had to lay off friends. Worse than that, I thought I might not be able to fund Isis and that the development of the technology would be delayed.

Scrip: Tell us about one change you effected in your organization that you believe has been invaluable?

SC: Some years ago I realized I have never clearly spelled out what we are trying to create culturally at Isis and the reasons why. We have invested extensively in this since and took a very good culture and turned it into an environment that I am really proud of.

Scrip: What was your first ever job?

SC: When I was 12 or so, I worked at a sort of teen dive called "The Tech Corner". It was across the street from the very large inner-city high school I attended, Arsenal Technology High School in Indianapolis.

Scrip: How did your first biotech/pharma job shape the rest of your career?

SC: I had the opportunity to lead the creation of the cancer program at Bristol and to simultaneously advance in academic medicine and science. That led to my being recruited to being the head of R&D at age 35 at SmithKline.

Scrip: What led you into the industry?

SC: My interest in bleomycin, an anti-cancer drug marketed by Bristol.

Scrip: At what point did you realize you were going to make a career in the pharma industry?

SC: The day I went to Bristol.

Scrip: You were later at SmithKlineBeecham (now GlaxoSmithKline), what did you learn there?

SC: I learned that my abilities are limited and that great things take time and disappointments to achieve.

Scrip: What was your favorite subject at school?

SC: History and literature.

Scrip: What is the one gadget that you can't leave home or office without?

SC: My iPad.

Scrip: What are you reading at the moment?

SC: Several mystery novels and a history of female spies in the Civil War.

Scrip: What is your favorite book, and why?


  • Huckleberry Finn by Mark Twain. This book is about the American journey towards fairness.
  • The Bear by William Faulkner. Again, this book is about the journey towards fairness and sacrifices that sometimes are needed.
  • Winter's Tale by Mark Helprin. This is a transcendental journey of love.

Scrip: What is your favorite piece of music, and why?


  • Rhapsodies by Ravel and Enescu
  • Keep a Knockin' – Little Richard
  • You've Lost That Loving Feeling – The Righteous Brothers
  • Hallelujah – Leonard Cohen
  • Michelangelo – Emmylou Harris

Scrip: Tell us one myth about the industry that you'd like to set straight.

SC: That drug discovery and development are easy.



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