David Shaywitz

In 2011, we were experiencing the ascension of technologies like the cloud and the smartphone.  Apps had become a thing: social network apps like Instagram (the iPhone “App of the Year” in 2011) and Twitter, utility apps like Evernote and Dropbox, navigation apps like Google Maps and Waze, and game apps like Angry Birds. Yet in medicine, as I wrote... Read More

Two weeks ago, I wrote about how difficult it is for R&D leaders to “pick winners,” despite the enormous incentives to do so.  I explained how we tend to underestimate the role of chance, and overestimate our ability to “domesticate uncertainty,” as Nassim Taleb and I wrote in the Financial Times in 2008.  Mostly, efforts to systematically improve success rates... Read More

Everybody reading this column knows that biopharma is a difficult business.  Biology is unfathomably complicated and figuring out how to introduce something into the human body that does more good than harm is a fiendishly difficult challenge. That’s why it’s important to recognize the occasional success. It reminds us what’s possible, and inspires us to think about how to achieve... Read More

Peter Thiel, the contrarian investor, had a favorite question for interviewees: “What important truth do few people agree with you on?” My answer: No one can pick winners in pharma R&D.  When I think of the most significant blockbusters in the industry involving novel mechanisms of action (follow-ons are a different story), I see a huge amount of luck on... Read More

A central challenge of R&D, like many disciplines characterized by rare, outsized success, is how to think about risk, as well as the contributions of luck and skill.  Two new books – How To Become Famous, by Cass Sunstein, and On the Edge, by Nate Silver, offer valuable perspectives. I’ll also highlight several articles that provide additional relevant insight, including... Read More

The phrase “assent without belief” has been used to describe the concept of going along with the outward manifestations of an ideology without true conviction. Most commonly, this is used to describe a familiar contemporary approach to religious observance.   It also seems to describe how the vast majority of biopharma colleagues view AI and other emerging digital and data technologies. ... Read More

Peter Attia is a prominent physician-turned-California longevity guru, and (to paraphrase Woody Allen) as California longevity gurus go, he’s one of the best, striving to remain grounded in science and data. Known for his popular book Outlive, and his affection for “rucking” (look it up), Attia is also the host of a long-form podcast called The Drive, and an engaging... Read More

“It was all mixed into one, enormous, overflowing stew of very real technological advances, unfounded hype, wild predictions, and concerns for the future.  ‘Artificial intelligence’ was the term that described it all.” – Cade Metz, Genius Makers   The buzzy excitement around artificial intelligence (AI), and most recently generative artificial intelligence (genAI), has inspired some biopharma leaders, exasperated many others,... Read More

While visiting my parents on Memorial Day weekend, I reflected on the wonder and joy of a life in medicine and science — theirs as well as mine.  Incredible Progress in Medicine My parents are academic physician-scientists at Yale Medical School, where they founded and continue to lead the Yale Center for Dyslexia and Creativity. Now in their early 80s,... Read More

The two broad categories of medical discovery that command the most attention are insights resulting from rare, informative genetic conditions (see here) and advances resulting from fortuitous observations.   A canonical example of the value of extreme genetic phenotypes is the patient with familial hypercholesterolemia who inspired Brown and Goldstein’s scientific pursuit of cholesterol metabolism and led to the statins. Similarly,... Read More

GLP-1 medicines are obviously having a real moment – medically and culturally.  These once-weekly injectables, which reduce appetite and result in significant, long-lasting (so long as you’re taking them…) weight loss, have been demonstrated to have a number of important health benefits beyond simply shedding pounds.  In March, Novo Nordisk’s semaglutide (Wegovy) was approved by the FDA for its ability... Read More

A main theme of this column – perhaps even the dominant theme – is how to operate in a power-law domain like drug development where there are few, outsized successes, where most efforts end in failure, and where it’s incredibly difficult to predict in advance how you are likely to fare. Earlier this week, I discussed the parallels between film... Read More

Film and pharma, like many creative endeavors, exist in a world of power law economics, where a handful of exceptionally successful products account for a massively disproportionate share of the total revenue.  Consequently, in both domains, there’s a powerful incentive to “pick winners.” Every studio head and every R&D leader tries desperately to do this.  But there’s a problem: as... Read More

Pharma colleagues: does this complaint sound familiar? This company is too bloated. It’s too slow. We have all these layers and layers of bosses where leaders at the top would decide on the strategy, and then it would just trickle down to the people who actually did a lot of the day-to-day work…. I am 10 layers below the CEO... Read More

As Bostonians tentatively emerge from the bleak cold of another New England winter and begin to search for signs of spring, we instinctively turn to the Red Sox.  Unfortunately, I am informed by my daughters that the team’s prospects appear dismal this season, so we’ll need to look elsewhere for hope. We might consider instead Boston’s other great preoccupation: biomedical... Read More

In this weekend’s Wall Street Journal, I review Death To Beauty, a new book by Dr. Eugene Helveston. It’s about the fascinating history of botulinum toxin and the California ophthalmologist, Alan Scott, who drove it into clinical use. The book review, of course, speaks for itself, but I wanted to highlight for TR readers an aspect of the story that... Read More

Spurred by several questions I’ve received from students and trainees, today’s year-end column examines some of the ways large biopharma companies are fundamentally different from small biotech companies and startups.  We’ll also ask whether biopharma can overcome new technology’s dreaded “productivity paradox” and learn, quickly, how to apply AI to accelerate drug development. Large Pharmas vs Smaller Companies (Including Startups)... Read More

Architects and Gardeners Most leadership offsites I’ve attended have included some flavor of personality assessment – not so much to formally classify us, but rather to make the point that different people have different styles, and to emphasize that you can’t assume everyone you work with approaches the world the same way you do.  In this spirit, I wanted to... Read More