20
Sep
2021

A Magical Time in the Presidential Range, Giving Back to Community

The Timmerman Traverse for Life Science Cares was everything I dreamed it would be.

Here’s a quick recap:

  • The team of 20 raised $706,000 to fight poverty
  • 51 sponsors participated
  • About 530 individuals contributed
  • We lucked out with the weather

For those unfamiliar, the Timmerman Traverse for Life Science Cares brought together a team of 20 biotech executives and investors to hike the Presidential Traverse in the White Mountains, Sept. 13-15, 2021.

This 20-mile trail goes up and across the most famous peaks in New England – Mt. Washington, Jefferson, Adams, and more. It’s demanding, as it involves 8,800 feet of net elevation gain. Our group was composed of some experienced hikers, and some enthusiastic beginners. We spent 2.5 days together on the rugged trails, with a couple nights in Appalachian Mountain Club huts.

This team felt some brisk wind in their faces. When the clouds passed on the high ridgeline, they got to bask in the sun, marveling at Mother Nature – at long distance and close range.

They pushed themselves physically. There were a couple long, 9 to 10-hour days on the trails. There were some tired legs. There were a couple sore ankles and knees, and a few moments when people needed to extend a hand to a teammate. That was never a question. This team was imbued with a spirit of kindness, generosity, and good humor from start to finish.

Most importantly, people in this group got to know some amazing biotech entrepreneurs and investors as people on a deep, human level. Friendships were formed that will last a lifetime.

See what a few members of the team had to say:

Vineeta Agarwala, general partner, Andreesen Horowitz

“It was amazing to see leaders across our biotech industry come together to raise funds to help bridge the unfortunately real gap between the medicines we develop, and the patients and communities who need access to them. I’m so grateful to be part of this dream team, and hopeful that the funds we are raising for Life Science Cares will help impact and support vulnerable communities across the country.” – Vineeta Agarwala, general partner, Andreesen Horowitz

“This team displayed innate motivation to help each other at those inevitable tough moments that arise for each of us along our journey. The same is true of our life science industry as we work together through Life Science Cares to help those in our community through their tough moments.” – Samantha Truex, venture partner, Atlas Venture

Art Krieg, founder and CSO, Checkmate Pharmaceuticals

“I’ve traversed the Presidential Range many times in all kinds of conditions over the years, but the Timmerman Traverse was the most fun yet: an incredible group of people raising money for an amazing cause in Life Science Cares – hope I can join you again next year!” – Art Krieg, founder and chief scientific officer, Checkmate Pharmaceuticals

“One unique thing about this group was the combination of discussing some aspect of new biology, cutting-edge drug development or drama in boardrooms while gingerly navigating the murderous talus of Mt. Adams et al.” – Jens Eckstein, managing partner, Apollo Health Ventures

“The industry is at its best when we come together to solve challenges: whether that is navigating boulders on Mt. Clay, or raising money and awareness for charities like Life Science Cares; a helping hand, teamwork, and support for one another are the hallmarks of success, and this team had them in spades.” — Jeb Keiper, CEO, Nimbus Therapeutics

Katherine Andersen, head of life sciences, SVB

“During dinner on Day 1, a lone hiker sat with us for dinner at the AMC hut and shared that he was on a solo trek to Georgia with hopes of arriving by Christmas.  Being about 300 miles in, we asked him what his biggest learning was so far.  His response was this: ‘It has reminded me what really matters, you know?  Family, a roof over your head, and food on the table.’ His comments became a drum beat that helped us put one foot in front of the other the rest of the week…True leadership is grounded in service and I count myself as fortunate to have been able to be part of the Timmerman Traverse team – a group that has really set the standard of excellence for giving back to the community.” — Katherine Andersen, head of life sciences, SVB

Reid Huber, partner, Third Rock Ventures

“We started as industry colleagues with an aligned philanthropic goal. We finished as friends, deeply connected through an experience none of us will ever forget and all of us will work to rekindle in our lives.” — Reid Huber, partner, Third Rock Ventures

“On the top of Mt Clay, there are no hierarchies, job titles, favored sons, or favored daughters. You are driven by your personal grit, your fellow climbers, and the beauty and challenges in front of you. We climbed for ourselves, we climbed for each other, but most importantly we climbed for the community being served by Life Science Cares. It was a bond we will never lose.” — Dave Melville, founder and CEO, The Bowdoin Group

Alice Pomponio, managing director, BrightEdge, American Cancer Society

“Not all who wander are lost. Together this team forged common ground to lift up those less fortunate, climbing new heights and supporting each other every step of the way.” — Alice Pomponio, managing director, BrightEdge, American Cancer Society

This isn’t a one-off thing. Since 2017, with the Everest Climb to Fight Cancer for Fred Hutch, I’ve been serving as a volunteer, mobilizing the biotech community to give back. Sometimes that involves giving back to the scientific community and sometimes that involves giving back to the wider community in which we all live and work.

Life Science Cares is a phenomenal organization that helps the biotech community leverage its resources – financial and human – to make a bigger impact in the fight against poverty.

I’m excited to see where this goes.

If you supported this campaign already, THANK YOU. If you are curious about getting involved in future trips, let’s talk.

There’s tremendous capacity for good in this industry. Let’s tap into it. luke@timmermanreport.com.

 

20
Sep
2021

What Should I Read? A Few Suggestions for Biotech Pros

David Shaywitz

Although we are all impossibly busy, most people I know in the biotech industry still make time to read books. 

Books may sometimes have a hard time competing with flashier forms of media in the online attention economy, but they aren’t going away anytime soon. This seems especially true now that so many titles are available in audiobook form, enabling us to appreciate them while traveling or exercising (my favorite time to listen). 

Perhaps because of my occasional reviews for the Wall Street Journal, I’m often asked by colleagues (and family members) for book recommendations. 

Here are a few suggestions, in three different categories: Tech and AI; Psychology and Wellness; and COVID.

Tech and AI

As AI has traversed through the hype cycle (hopefully we’re beginning to slowly climb the Slope of Enlightenment), we’ve been inundated by books about how we got here, what’s happening now, and where AI might be headed. 

Initially, many authors focused on what might be called the technology transformation imperative — some version of “tech is taking over the world; the potential is enormous.”  Some focused on the opportunity: leverage data and emerging technology and you can do incredible, previously unimaginable things, argued Erik Brynjolfsson and Andrew McAfee in Second Machine Age (2014), see here.

Others emphasized the urgency of action: ignore technology and your business will go extinct, Tom Siebel argued in Digital Transformation (2019), which I discuss here. Some experts, like Jim Manzi, have offered more balance.

Over time, the tone of the discussion seemed to perceptibly shift. The limitations and risks of the technology increasingly attracted the attention of authors, reflecting a similar concern by many in the field (the so-called “Tech-lash”- see here).

Brian Christian, author, “The Alignment Problem.” Photo credit: Eileen Meny

The challenge of getting AI do you what you want it to do was discussed with particular eloquence by Brian Christian in The Alignment Problem (2020), which I reviewed for the WSJ, and would highly recommend. In 2021, I reviewed a raft of AI-related books that shared the sense the technology was not an unalloyed good, and needed to be considered and evaluated with nuance. 

Of these, the best overview for the general reader is probably Cade Metz’s Genius Makers: The Mavericks Who Brought AI to Google, Facebook and the World. It’s a captivating and approachable history of Deep Learning and the researchers behind it.

Psychology and Well-Being

As TR readers will recall, I’ve become increasingly interested in positive psychology, a preoccupation that has clearly puzzled some colleagues. One physician-scientist in pharma affectionately refers to it as “crystals in Sedona,” and tells me “You’re in Boston now, not California. Time to get real.” 

Positive psychology, it turns out, is an academic discipline that was largely developed, and then deliberately reified, through the remarkable determination of one indominable scientist: University of Pennsylvania psychologist Martin Seligman. Today, many are familiar with aspects of this field through the wildly popular Happiness Lab podcast, hosted by Yale Professor Laurie Santos (and which I highly recommend), and through her similarly popular Coursera course, “The Science of Well-Being” (it’s also fantastic). I’ve been told Seligman’s Coursera offering on Positive Psychology is superb as well. 

This summer, I completed a virtual, week-long course offered jointly by professor Laura Kubzansky and colleagues at the Harvard School of Public Health, and by professor Andrew Steptoe and colleagues at University College London, entitled “Exploring the Linkages Between Mental Well-being & Physical Health Outcomes.” Crystals weren’t on the syllabus, which focused instead on a critical review of the data and methodology in published, peer-reviewed studies. 

I came away from the class with a renewed appreciation for both the extraordinary difficulty of durably driving healthy behavior change, and the value of positive psychology interventions – PPIs — as a promising tool in our arsenal (as I’ve recently discussed). Examples of PPIs include “savoring” (taking time to deliberately appreciate an experience); unexpected acts of kindness; expressions of gratitude; enhancing social connections; also exercise and sleep. The potential of PPIs as distinct tools hasn’t been lost on digital health companies focused on mental health and behavior change; one – Happify – is explicitly based on such interventions, and a suite of PPIs are central components of many other offerings as well.

Seligman has written several books on positive psychology, including Authentic Happiness (2002), a title he says he dislikes but which was forced on him by his publisher. In 2018, he published The Hope Circuit, his autobiography. 

Both books are unbearably, and almost unimaginably, narcissistic, on the one hand, but also, in their own way, engaging (at least at times), and provide a remarkable window into the internecine world of academic politics, and what it takes to navigate them successfully. (Readers may also confront the question discussed in my last TR piece, and that Shira Ovide has written about so eloquently in The New York Times: can you have the positive qualities of transformative entrepreneurs – including entrepreneurs of ideas – without some of the more difficult attributes?)

Several other books I enjoyed after learning about them from the Santos podcast, and found particularly worthwhile, include Good Habits, Bad Habits (2019) by USC professor Wendy Wood, and Stumbling on Happiness (2006), by Harvard’s Daniel Gilbert. Through my children’s school, I also discovered Think Again, by Wharton Professor Adam Grant, about the value of continuously rethinking ideas. 

Grant’s work connects not only with a central theme of Reid Hoffman’s Masters of Scale (discussed in WSJ here, and in TR here), and of Pixar’s former CEO Ed Catmull (I discuss here and here), but also with legendary scientists. In Horace Freeland Judson’s epic history of molecular biology, Eighth Day of Creation, Francis Crick tells the author “Just as important as having ideas is getting rid of them.”  (Nerd alert: this was one of the quotes I used in my high school yearbook.) 

While Grant’s message is critically important, at times his argument feels a bit tidy. While he’s unquestionably right that not getting unduly wed to ideas is important, it’s not clear that there’s any way to discern reliably when you need to persist in an uphill battle and when you should drop an idea and move on. 

As I wrote in my WSJ review of Safi Bahcall’s Loonshots, a book about cultivating innovation in organizations, and discussed in Forbes:

“The uncomfortable truth is that doing something new is risky, and it is often impossible for an organization to determine, in advance, whether an innovative team is working on a hit or a flop. As the late Harvard researcher Judah Folkman used to tell his students: ‘If your idea succeeds, everybody says you’re persistent. If it doesn’t, you’re obstinate.’”

In short: it’s relatively easy to craft narratives around failures to re-evaluate, or successes associated with thinking again, but there are compelling, equal, and opposite narratives as well, and it may not be possible, in the moment, to know which path will be best. At times, rethinking could save your company, at other times, you’d have been better off brashly forging ahead, and it simply may not be possible to know in advance which approach is best.

COVID

COVID, visibly, has disrupted the world and consumed our attention. The pandemic – both the virus and our response to it – has threatened our physical and mental health, our economic health, and the health of our relationships with one another. 

Our explanatory models for COVID have become intertwined with our identities, calling to mind Miles’ Law: where you stand depends upon where you sit.

We’re desperate to understand “what went wrong,” ostensibly to prevent future pandemics, but also to satisfy our fundamental human need for some explanation of how this terrible thing could happen.  Several books have already been published on the pandemic, and hundreds more are sure to follow. 

Two that are particularly worthwhile: Michael Lewis’s The Premonition (published May 2021), and Scott Gottlieb’s Uncontrolled Spread, out this week (note: Scott, a colleague at the AEI, had shared a completed copy of his manuscript with me ahead of publication). 

Lewis has a remarkable gift for accessing complex and unwieldy subjects, like sabermetrics (Moneyball) and the financial crisis (The Big Short) by focusing the story on seemingly peripheral characters, typically unheralded individuals who emerge as protagonists. In The Premonition, he introduces us to an eclectic crew of physicians and scientists who both individually and collectively were striving to help the nation recognize the pandemic and respond to the threat. Through their efforts, we appreciate the dimension of the challenge and the difficulties of developing an effective response.

Scott Gottlieb, author, “Uncontrolled Spread.”

Gottlieb’s approach seems an ideal complement to Lewis’s. As FDA commissioner from 2017-2019, and a familiar presence on television and social media, Gottlieb seems to have almost Bob Woodward-level access to all the key players in the federal government and industry.

He is able to present a remarkably comprehensive and insightful description of the evolution of the pandemic, and our national struggle to develop a strategy and execute a plan. Uncontrolled Spread is as compelling as it is concerning, and represents an ideal starting point for readers hoping to understand how we got here.

Both Lewis and Gottlieb agree on several fundamental points. Perhaps most importantly, the authors seem to emphatically conclude that the CDC is intrinsically a fusty, academic, highly bureaucratic organization not culturally suited to respond with real-time actions to prevent suffering and death in a fast-moving crisis like COVID-19. 

One of Lewis’s protagonists, Dr. Charity Dean, a state public health official in California at the time, writes, in response to a proposed COVID response strategy, “The single most important part of this plan is IT IS NOT RUN BY THE CDC. It is run and overseen by an entity with actual experience in front line warfare in outbreaks.” In both books, the CDC is portrayed as an agency that might write a superb New England Journal of Medicine paper characterizing an epidemic — well after the acute danger has passed. 

But another take-away that emerges from both books is that a key contributor to the challenge of responding to situations like COVID is the complex and often conflicting motivations driving human behavior.

For example, as Gottlieb discusses, China’s suppression of information clearly delayed the global appreciation of the danger posed by the virus, and contributed to its worldwide spread. But as he also reveals, the suppression seems to have occurred at every level – not only did Beijing punish physicians who tried to share knowledge of the outbreak in China, but even within China, Gottlieb writes that “information was being held by provincial officials” who were evidently concerned about alarming the central government. 

Both Gottlieb and Lewis also highlight a number of examples where the “villain” seems to be a human being with feet of clay operating within the rigid constraints and often perverse incentives of bureaucratic structures and processes. 

For instance, Lewis describes the challenge faced by researchers from the Chan-Zuckerberg Initiative attempting to provide free COVID testing – in this case to the Zuckerberg San Francisco General Hospital:

“How much is it going to cost?” asked the woman at Zuckerberg General, after the team at Chan Zuckerberg had explained their new COVID-19 testing lab.

“It’s free,” said Chan Zuckerberg.

“There was this super-long pause,” said Joe (DeRisi, the scientist who led the development of the test and) who was on the line.

“We don’t know how to do no-cost,” said Zuckerberg.

“What do you mean?” asked Chan Zuckerberg.

“It shows up as an error in the hospital computer if we put in zero cost,” the hospital official clarified.  “It won’t accept zero.”

“Can’t you put like one-tenth of a cent?” asked Joe.

They couldn’t.

And here we are.

15
Sep
2021

Hero Narratives Inspire Entrepreneurs But Obscure Uncomfortable Trade-Offs

David Shaywitz

In today’s Wall Street Journal, I discuss Reid Hoffman’s Masters of Scale, a new book by the renowned Silicon Valley entrepreneur (PayPal, LinkedIn), investor (Facebook, Airbnb), and podcast host that proposes to distill the secrets of successful business and social entrepreneurs. 

The review speaks for itself, of course, but Hoffman’s account, and others like it (there are many – for example, Guy Raz’s delightful How I Built This) present a seductive portrait of entrepreneurship that TR readers should approach with caution.

Hoffman appears to earnestly believe that building a company represents, in his words, a “hero’s journey.” Often, he presents their adventures through this narrative template, offering carefully crafted dramas that, like an Aesop Fable or a tale from Greek mythology, tidily convey a handy lesson and an appealing moral at the end. 

Many of these founder stories have in their own way approached the level of mythology, serving as familiar touchstones for the startup community, and inspiration for would-be heroes seeking their own ascent to Olympus.

Reid Hoffman

Much of Hoffman’s advice seems authentically insightful, the result of hard-won experience.  One example: his suggestion that successful entrepreneurs need to “learn to unlearn,” since the strategies and approaches that take the company to a certain point might not take them to the next inflection point.

Here, Hoffman echoes one of the most powerful points former Pixar CEO Ed Catmull makes in Creativity Inc., (see here, here) and also shared with me in conversation: success, especially in any creative domain, isn’t formulaic – and intrinsically, can’t be.  Just because you’ve managed to come up with one exceptional movie, say, doesn’t mean that now you know how to create the next imaginative film. 

Catmull writes,

“People want to hang on to things that work—stories that work, methods that work, strategies that work. You figure something out, it works, so you keep doing it—this is what an organization that is committed to learning does. And as we become successful, our approaches are reinforced, and we become even more resistant to change.”

He goes on to argue that change is essential, and that creative teams have to reinvent themselves constantly. This is also a point University of Pennsylvania psychologist Adam Grant emphasizes repeatedly in his popular new book, Think Again

I’ve previously contrasted this to the tendency of many pharma companies to fixate on a successful new drug and look for the magic, repeatable formula for success, a golden methodology or durable template that might serve as a model for future drug development. I’ve seen many examples of this ending badly. 

As instructive as Hoffman’s advice can be, his founder tales can also be misleading.  Many of these stories – oft-repeated legends by now – are so compelling it can be easy to forget just how sculpted and sanitized most are. For example, in a chapter on the importance of establishing a good company culture, Hoffman extols the approach taken by a Boston marketing startup, where the executives emphasize all the right things.  Yet this feel-good adulation contrasts sharply with journalist Dan Lyons’s lived experience at the same company, savagely documented in Disrupted.

Entrepreneurs seeking balance would do well to read Ali Tamaseb’s SuperFounders, discussed here, which offers a relatively quantitative look at factors that are (and are not) associated with founder success, defined in this context as achieving a billion-dollar valuation.  The book, with its more quantitative perspective, is especially valuable as a counterpoint to narrative-driven stories that are so digestible, and hence, popular. 

For example, while heartwarming accounts of founders doggedly pursuing, and fulfilling their life passion attract journalists and engage readers, Tamaseb points out that many successful founders discovered their purpose only after they landed on something they toiled at for years happened to take off (see here). 

Tamaseb very deliberately seeks to tease conventional wisdom away from established fact; for example, many investors (including, explicitly, Hoffman) confidently advise individual would-be founders to find a partner. 

However, as Tamaseb explains, his data reveal “no correlation between number of cofounders and success.” While he notes that “most successful solo founders either had a successful exit before or were big-name executives at a large company,” he still is reluctant to advise first-time founders without this background to reflexively partner up. 

“I would say to a first-time founder not to force finding a co-founder just so that they have a co-founder,” he tells me.  “Chances are their company will fail because of conflict with a person they don’t know. But if there’s someone that adds to their company something they can’t bring and they know how to work together, it’s probably beneficial to them to pair up.”

Aspiring founders seeking pragmatic advice also might discover an essential resource in Jeffrey Pfeffer’s unvarnished studies of leadership. A professor at Stanford’s Business School, Pfeffer has spent his entire academic career rigorously studying how leaders actually acquire power; for around four decades, he’s taught a popular course on the topic “Paths to Power.” He’s also written several books on this, including Power, and Leadership B.S. – both of which are required reading; his forthcoming Seven Rules of Power promises to be similarly relevant.

Jeffrey Pfeffer, Thomas D. Dee II Professor of Organizational Behavior, Stanford Graduate School of Business

(Note for readers in universities: there a classic paper, “How To Swim With Sharks,” written by the late John Hopkins professor of bioengineering Richard Johns under the pseudonym Voltaire Cousteau, that offers similarly concise, and equally essential, advice tailored to aspiring academic leaders.)

Pfeffer’s basic point is that the qualities that leaders use to acquire power are often (and nearly always) different that the noble attributes leaders tend to extol and pay homage to after power is acquired. 

(Here Pfeffer echoes William S. Gilbert’s legendary Pirate King, who first observed over a century ago, “But many a king on a first-class throne/If he wants to call his crown his own/Must manage somehow to get through/More dirty work than e’er I do.”)

With example after example, Pfeffer points out that powerful leaders very deliberately craft their own history after the fact. “Once you become successful and powerful,” he writes, how you got where you are will be mostly forgiven, forgotten, or both.” Consequently, he is especially suspicious of tidy success narratives – especially when meticulously crafted by those who’ve already achieved power. 

The animating conceit of Hoffman’s Masters of Scale is that entrepreneurs can realistically hope to pretty much have it all. They can possess the aggressive, expansionist mindset and indomitable determination to enables their startup to achieve explosive growth, yet, through diligent stewardship of culture and leadership, they also can accomplish this while avoiding nearly all the toxicities that have given so many rapidly-growing tech companies a bad name. Examples here include Facebook’s deliberate prioritization of growth to pursue “domination,” as I’ve discussed here, or the notorious bad behavior of founders like Uber’s Travis Kalanick.

Hoffman, explicitly, and to his credit, acknowledges that entrepreneurs often need to make tough choices, and occasionally navigate through transiently uncomfortable situations.  He describes executives in the early days of PayPal ignoring clamoring customers so the team could rapidly build the next iteration of the platform.  “You need to think about future customers as well as your current ones,” he says, adding he’d make the same decision again.

At the same time, he emphatically condemns the behavior of Kalanick, for example, and suggests startups avoid these outcomes by placing an early emphasis on culture, and demanding a different sort of leader.

It’s easy to read Hoffman and nod along with his comforting assurances that a startup can rise to prominence without using especially objectionable means to get there.

But then, we think of Pfeffer’s many uncomfortable examples of how leaders actually acquired power.  We’re compelled to ask ourselves whether we should really expect a startup’s path to power is likely to be that different. It seems more than possible that the traits required to grow a fragile, nascent startup into a global powerhouse may be conspicuously different, and considerably less congenial, than the traits the company, its management, and its investors typically choose to highlight after the fact.

In a particularly eloquent meditation on founders, Shira Ovide of the New York Times writes that while she’s angry at founders who behave badly, “deep down, I also wonder whether unscrupulous, boundary-pushing executives are an inescapable part of innovation — rather than an aberration.”

She’s also not sure “if curtailing the excesses would also curb the ambition that we want. Sometimes the zeal to imagine ridiculously grand visions of the future brings us Theranos. And sometimes it brings us Google. Are these two sides of the same coin?”

Ovide sees Tesla CEO Elon Musk as an example of both extremes. He is an outrageously audacious entrepreneur, whose vision for electric vehicles has delivered “potentially planet-transforming change.” At the same time, Ovide writes, “Musk has endangered people’s lives by overhyping driver-assistance technology, has repeatedly over-promised technology that hasn’t panned out and has skirted both the law and human decency.”

As Ovide’s colleague Cade Metz highlights in Genius Makers (my WSJ review here), such hype is not unusual among the Silicon Valley elite.  These visionaries, Metz writes, recognize that “ideas might fail. Predictions might not be met. But the next idea wouldn’t succeed unless they, and everybody around them, believed that it could.”  

Thus the wrenching question Ovide ponders: “maybe it’s impossible to separate the reckless carnival barker who deludes himself and others from the bold ideas that really are helping to change the world for the better.”

Hoffman, fundamentally, wants to assure entrepreneurs it’s possible for startups to rapidly soar to extraordinary heights, and behave relatively admirably while doing it. I want to believe this – of young companies, visionary founders, powerful corporate executives, prominent academic leaders, ambitious politicians. We all do. But, like Pfeffer, I struggle to get there, and find myself in the same boat as Ovide, who concludes, ruefully, “I just don’t know if we can separate the wonderful from the awful.”

12
Sep
2021

Turning Around COVID Diagnostics. Mara Aspinall on The Long Run

Today’s guest on The Long Run is Mara Aspinall.

Mara is a veteran diagnostics executive, investor, and educator. She’s a venture investor with Bluestone Venture Partners, the CEO of Health Catalysts (a consulting firm), and the co-founder and professor of the practice of biomedical diagnostics at Arizona State University. It’s the only program of its kind in the country, designed to provide graduate level education at the intersection of technology and business in diagnostics.

Mara Aspinall, managing director, BlueStone Venture Partners; professor of the practice, biomedical diagnostics, Arizona State University

Before all that, she cut her teeth in diagnostics as the president of Genzyme Genetics before its sale to LabCorp, and as CEO of Roche’s Ventana Medical Systems – when it was in the early days of developing a companion diagnostic strategy to pair up with targeted therapies.

Mara is simply one of the smartest and most experienced people I know in the diagnostics business. I have sought her perspective on the crucial – and undercovered – diagnostic testing aspect of the pandemic response. She has written a few excellent guest editorials on Timmerman Report that I’ve been privileged to edit. I’ll post links to those articles on the show summary at Timmerman Report.

This episode was recorded Friday, Sept. 3. Regular listeners know this isn’t a news-oriented podcast, but Mara is a COVID-19 diagnostics expert and this is an undercovered aspect of the pandemic response. I did notice in the days after this recording that President Biden and others have started talking more about increasing efforts to expand testing. So if this show feels a little dated by the time you listen, just recognize that everything moves fast in the pandemic. I think quite a lot of what Mara had to say will still be relevant throughout the fall, and far into the future.

Before we get started, a word from the sponsor of The Long Run – Answerthink.

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Now, please join me and Mara Aspinall on The Long Run.

7
Sep
2021

Base Editing for Therapeutics: John Evans on The Long Run

John Evans is today’s guest on The Long Run.

John Evans, CEO, Beam Therapeutics

John is the CEO of Cambridge, Mass.-based Beam Therapeutics. The company was founded a little over three years ago to develop several types of DNA base editing developed in David Liu’s lab at Harvard University, along with an RNA base editor platform developed by Feng Zhang, at the Broad Institute of MIT and Harvard.

The gist of the idea, which John describes well, is that it’s possible to make precise gene edits with an adapted form of CRISPR technology that doesn’t need to cut out a whole disease-related gene. It can achieve a therapeutic goal by acting in an even more precise way – by finding an exact spot in the 3-billion base pair genome, and modifying a single chemical base of DNA.

Beam is seeking to put different pieces of the technology puzzle together, with different types of editing, different modes of delivery, and thinking through how these combinations make the most sense for different therapeutic indications. When does it make sense to do edits outside the body (ex vivo), and when it’s better to do the edit inside the body (in vivo)?

The company’s first two programs aimed for the clinic, BEAM 101 and BEAM 102, are for sickle cell disease and beta-thalassemia.

It’s heady stuff. As it matures and becomes closer to becoming a real thing that might become an FDA approved product, it’s likely to generate a lot of fear and controversy in the public. I asked John a bit about that toward the end of the conversation.

Before we get started, here’s a word from the sponsors of the show.

 

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Now, please join me and John Evans on The Long Run.

31
Aug
2021

Meet the Climb to Fight Cancer Postdoctoral Fellow: Aleena Arakaki

I’m excited to announce that the first Climb to Fight Cancer postdoctoral fellow has been selected. This is a position designed to advance the careers of young scientists from traditionally underrepresented minority groups.

Aleena Arakaki is the first recipient of this postdoctoral award. She is a Kanaka Maoli (Native Hawaiian) woman.

Aleena Arakaki, postdoctoral fellow, Fred Hutch

Before describing Arakaki’s background and research, here’s what the program is about. This fellowship was created by generous donations in February, by the alumni of the 2019 Kilimanjaro Climb to Fight Cancer expedition that I organized as a volunteer for Fred Hutch.

That campaign raised $1.6 million for cancer research. That awesome group of 27 biotech professionals formed close bonds on a trip to Africa’s highest mountain. They stayed in touch.

When the racial justice protests swept the country last year, they wanted to do more to uplift people from underrepresented minority groups in science.

Together, we raised more than $135,000 to create this program with Fred Hutch.

This program provides funding to support a postdoc position, with an added bonus. The recipient can join one of the future Climb to Fight Cancer expeditions that I organize for the biotech community.

It’s designed to be a great way for a young scientist to advance his or her research, while also building an exceptional industry network.

Arakaki received her bachelor’s in science in Cellular and Molecular Biology, with honors, from Seattle University in 2014. She went on to get her PhD at UCSD, working in the lab of Dr. Joann Trejo. Aleena’s graduate work focused on the regulation and molecular mechanisms of GPCR activation of the Hippo pathway in metastatic breast cancer.

You can read her June 2018 publication in the International Journal of Molecular Sciences, titled “GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling.” And this April 2021 paper in The Journal of Cell Sciences on “α-Arrestin ARRDC3 tumor suppressor function is linked to GPCR-induced TAZ activation and breast cancer metastasis.”

Arakaki received a prestigious HHMI Gilliam Fellowship as a grad student, and is now working as a postdoc in the Gujral Lab at Fred Hutch. She was selected by the Office of Diversity, Equity and Inclusion as a Presidential Postdoc Fellow at Fred Hutch, and her research is partially supported by the Translational Adult Glioma Grant Award from The Ben and Catherine Ivy Foundation.

Her research proposal is focused on ependymomas — cancers of the central nervous system. She’s specifically looking at YAP1 gene fusions, and whether they can be targeted with existing kinase inhibitors, including verteporfin and sorafenib combination treatment.

I’m excited to see where the research leads, and whether it will light the way for her to discover a useful new treatment for patients.

20
Aug
2021

Giving Back and Experiencing Nature

Sometimes we need to get away from work, and the news, to recharge our batteries. August is traditionally that time of year for me.

I just got back from the summit of Mt. Baker (elevation 10,781 ft) in the North Cascades of Washington. It was another successful mountain trip with terrific biotech people – entrepreneur Julia Owens, investor Dan Bradbury, venture capitalist Nancy Hong, and Ardem Patapoutian (Nancy’s husband and a researcher at The Scripps Research Institute).

We were guided by Lakpa Rita Sherpa, Jangbu Sherpa and Dawa Yangzum Sherpa. They are some of the most accomplished Sherpa mountain guides in the world. Lakpa and Jangbu are good friends of mine, and were part of the guiding team on my Mt. Everest summit expedition in 2018. Dawa Yangzum is famous for being the first Nepali woman to summit K2, and the only woman of color on the all-star team of mountain athletes sponsored by The North Face.

This climb was a fundraiser for the Alpine Ascents Foundation, which supports education for 55 Sherpa schoolchildren in Nepal. Together, we raised $20,000 for the cause.

There were some challenges. We ran into 50 mph winds. We had to avoid some massive crevasses. It was a long, low-visibility day on the icy glaciers of the North Cascades. But everyone made it up and down safely, and had a wonderful time. See a couple photos (that’s me and Julia Owens on the very windy summit).

This isn’t my only outdoor adventure which mobilizes the biotech community for a good cause in 2021.

Next month, I’m taking a team of 20 biotech executives and investors on the Presidential Traverse hike in New Hampshire. We’ll cover more than 20 miles, and gain more than 8,000 feet of elevation as we cross over the summits of Mt. Washington, Mt. Jefferson, Mt. Madison and more.

This Timmerman Traverse is a fundraiser for Life Science Cares. It’s an organization that supports an array of outstanding nonprofits in the Boston area who do critical work on homelessness, hunger, job training, education and more. LSC is now expanding its model to other biotech hubs — the San Francisco Bay Area, San Diego, and Philadelphia.

Life Science Cares provides a way for the biotech community to support the most vulnerable people in our communities, and help them get back on their feet.

The Timmerman Traverse team has raised more than $479,000 so far – well on our way to smashing the $500,000 team goal. I’m proud of this group of dedicated biotech leaders, and grateful for the generous support of so many people.

If you’d like to learn more about this trip and this team, watch this 3-minute video created by SVB, the lead sponsor of the Timmerman Traverse for Life Science Cares.

Doug Fambrough of Dicerna, Katherine Andersen of SVB, Alice Pomponio of the American Cancer Society, Samantha Truex of Atlas Venture, Dave Melville of The Bowdoin Group all have powerful messages about why they’re doing what they do. Art Krieg of Checkmate Pharmaceuticals and Jeb Keiper of Nimbus Therapeutics also have potent video testimonials at the end.

You can click here to see who’s on the team, and make a contribution directly to their fundraising campaign through the JustGiving.org platform.

There is tremendous capacity for good in the biopharmaceutical industry. Let’s show it.

16
Aug
2021

Vaccination and the Delta Variant: Four Steps Forward, Two Steps Back

Larry Corey, MD

The news is all about Delta, Delta, Delta, for good reason.

The variants are forcing us to ask and answer, again, a whole set of uncomfortable questions.

Sobering findings of the past few weeks have shaken both the American and scientific psyche. People have had to re-assess their perceptions about the COVID-19 vaccines, and the re-emergence of an epidemic many thought was over. Many of us have had to come to terms with how life can sometimes just be complicated.

It’s been a scientific and emotional roller coaster. In the spring, we saw the Alpha variant, which was two times more infectious than the ancestral strain. That was followed by Beta, which was eight times more resistant to laboratory assays and to neutralization with therapeutic antibodies in the petri dish. That variant was worrisome, because it was more capable at resisting vaccines. We were lucky because it was outcompeted by Alpha – a variant that the vaccines could handle.

Now Delta is here and just ripping through both of them, like a hot knife through butter. It’s replacing Beta with the same rapidity that it replaced Alpha and all the in-between variants. It’s now the dominant variant in the US, showing up in more than 90 percent of positive cases.

So, what is it about this Delta, or what I should say, many Deltas?

What we’re seeing is this scientifically fascinating, but epidemiologically disconcerting change in the virus that’s happened at an incredibly rapid pace. Delta has some new characteristics which make it a formidable foe. It’s much more infectious to others; initial viral loads in the nose seem to be somewhat higher than previous strains with more rapid spread into the lungs and other organs within the body.

It is clear that the amount of virus required to infect others is lower, making transmissibility to household and casual contacts more efficient than the other variants. The average person who contracts a Delta infection transmits the virus to between 5 and 9 other people – making this variant far more infectious than the original ancestral strain from a year ago.

Case numbers, predictably, are quickly increasing. Younger adults are being hospitalized. ICUs are filling up. Most disconcertingly, we are seeing more children being admitted in our pediatric hospitals. When we look at who’s in the hospital among adults, we see about 95 to 98% are unvaccinated. The same pattern is seen with children. COVID-19 Delta strain is a hospital epidemic of the unvaccinated.

Yes, we are now seeing outbreaks of Delta in which vaccinated people are infected, such as the one from early July in Provincetown, Massachusetts. These outbreaks involve two behaviors we’ve seen that result in super-spreader events—crowding and indoor revelry with drinking and eating and no masks. Eating, drinking, shouting, singing—spraying forth, shall we say, produce a density of unseen viral particles in the air that people inhale over and over again.

These behaviors are the food of the virus—a heavy smorgasbord of food: all advantageous to the virus. The result is that we are seeing humans get infected. For the vaccinated, this means just mild infection. But for the unvaccinated, we are seeing rapid spread of the virus to the lungs and other parts of the body.

With more than 100,000 cases a day being tallied nationwide, it’s clear we need to take some new countermeasures to slow the spread.

We’ve seen a necessary reintroduction of masking. Just when many people were ready to celebrate, or breathe a sigh of relief, many of us are now back in an anxious position. Questions that we might have thought were settled a month ago are suddenly back in play.

Will our children be able to safely go back to school? Can we safely go back to work? Will we ever be able to relax and enjoy dinner indoors again with friends, extended family, or in professional settings?

Delta is disconcerting to all of us.

Last week, I cancelled a CoVPN (COVID-19 Prevention Network) scientific meeting in October—one that I’d been eagerly planning and anticipating for months. We wanted to meet and celebrate/review the work the network has done in developing effective COVID-19 vaccines at unprecedented, record-setting pace.

The success of the program and the hard work and toil have shaped the careers of many scientists on this team. In some ways, it has shaped entire worldviews. We wanted to revel in the camaraderie of the team’s success and do so in person. But it was clear—even though the event required vaccination to attend, no one wanted to come to Seattle to celebrate with the possible risk it would carry if anyone contracted Delta and had to be quarantined away from home.

Let’s look at vaccination and Delta as it relates to the US:

  • The mRNA and Janssen vaccines both are highly effective against death and hospitalization (greater than 90 to 98%).
  • The protection from getting symptomatic COVID-19 appears to be a bit less with the Delta variant—studies show a range from 85% to 40%–and this may differ by time post vaccination. But in all studies the severity of illness is markedly less—the immune system of vaccinated persons can rapidly clear Delta. As noted above, severe disease among the vaccinated in the US with the mRNA or Janssen vaccines is rare.
  • Transmission to others from vaccinated persons can occur, but it is less than from the unvaccinated population, although we have not yet demonstrated how much less.

So, yes, one can still get infected with Delta despite being vaccinated if one doesn’t use precautions. That’s a fact. But a bigger fact is that you won’t get very sick, and you can reduce the risk of acquiring COVID-19 and spreading it if you wear a mask.

Perhaps we shouldn’t have been surprised. We understood that reducing acquisition of COVID-19 was a harder goal than ameliorating disease. But we do know the vaccines work and countless lives have been saved by them. So, the vaccines have markedly changed the dynamic of our thought process, but maybe what we need is to change our expectations.

What do I mean by that?

Well, the virus is teaching us another important lesson—its amazing speed to adapt. It’s hard to understand how a virus like this is rolling through the world. But rolling through, it is. Recent data out of Israel estimates that every six to nine days the Delta infection among its population doubles. As Israel has the highest percent vaccination rate (with Pfizer/BioNTech mRNA) of any adult population in the world, this is at first glance surprising. However, not when one recognizes that younger people are not yet vaccinated, and it’s the unvaccinated who are the main fuel for that kind of rapid spread.

Why is it so transmissible? What selective pressure is it under? Delta doesn’t have the obvious neutralization-resistant mutations. What part of the human immune response that you get from vaccination is being delayed by the Delta variant? Will boosters actually slow it down or is it really more important to focus our efforts on reaching the unvaccinated?

These are all scientific questions needing answers. As Israel has made the decision to boost its elderly population, some data about the role that boosting can play in reducing spread will be obtained.

But the boosting issue is a bit of a diversion from the main issue in our country, which is, how do we reduce the spread of this highly infectious variant? 

Do we need a national mandate for vaccination? Is it a personal choice to vaccinate or not? Or do we all have a societal obligation to not be the fuel to this ongoing forest fire? The unvaccinated in some respects are an unsuspecting accomplice to the arsonist at large—they serve as bone-dry tinder for the lighted match.

Should we rethink this?

Our body politic is focused on extreme individualism, and isn’t allowing a universal approach to public health. In such an environment where political leadership is limited, do our corporate leaders who can mandate vaccination step up to the plate?

There are some who are pointing to government action, namely through a full approval of the vaccines by the FDA. But does anyone really believe that the Emergency Use Authorization is that much different than the FDA licensing it under a full Biologics License Application? Yes, there are important steps to licensing the medication so that there is consistency from lot to lot in manufacturing. But at 400 million vaccinated and growing daily, we have ample safety and efficacy data.

So, yes, official product licensure is, to this author, not an appropriate reason to hold back mandated vaccination. We already know the vaccines are extraordinarily effective, and powerful tools for fighting back against the pandemic. Each day the documentation of the positive effect of the vaccines grows, and we understand that the virus is continuing to mutate. Cutting off the fuel to the fire is really the only way to slow down the rate of mutational alterations.

It is true that the Delta variant has swept in like a cold, damp morning shrouded by fog. And it’s left us with a bit of a shiver. But like all days, morning turns to afternoon and the sun gets higher in the horizon and some of the fog lifts. Although Delta has taken us two steps back, a much more important step forward is to continue to vaccinate as many of our citizens as we can – here in the US and around the world.

Once we do, Delta may move itself two steps back, putting us once again two steps forward toward pre-COVID-19 normalcy.

Dr. Larry Corey is the leader of the COVID-19 Prevention Network (CoVPN) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID-19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.

9
Aug
2021

Better Cancer Drugs for Kids: Julie Grant and Sam Blackman on The Long Run

Today we have a pair of guests on The Long Run — Julie Grant and Sam Blackman.

Julie Grant, co-founder, Day One Biopharmaceuticals; general partner, Canaan Partners

Julie is a venture capitalist – a general partner at Canaan Partners. Sam is a pediatric oncologist and drug developer. After a routine business meeting, they realized they had something in common. They both believed that the pharmaceutical industry can — and should – find a way to do a better job of developing cancer drugs for kids.

So they did what scientific entrepreneurs do. They took a gamble, and tried to figure out how to do something that hadn’t been done before. They poured a lot of time and energy into fleshing out a concept of a purpose-built precision oncology company that puts the needs of children first. That concept became San Francisco-based Day One Biopharmaceuticals. Julie is the board chair, and Sam serves as chief medical officer.

Sam Blackman, MD, PhD; co-founder and chief medical officer, Day One Biopharmaceuticals

I wrote about the company a couple times for Timmerman Report a couple times before it went public, and subscribers can go back and read those articles from May 2020 and February 2021. The company now has a market valuation of more than $1.5 billion on the day of this recording. Side note here–if Day One is successful, its work could spill over and benefit adult cancer populations as well – but I digress.

Julie and Sam are creative, tireless people committed to helping kids with cancer. I think you’ll enjoy hearing them talk about this new journey in applying science for the betterment of human health.

Before we get started, here’s a word from the sponsor of The Long Run.

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This is an excerpt from a love letter written by Leonardo to his cells. One of several
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Watch Leonardo read his amazing love letters at thermofisher.com/GibcoLoveYourCells.

Now please join me and Julie Grant and Sam Blackman on The Long Run.

4
Aug
2021

Tachi Yamada, Physician-Scientist-Biopharma Industry Leader, Dies at 76

Tadataka “Tachi” Yamada, a distinguished physician-scientist who became a biopharmaceutical industry leader and a deeply respected advisor to biotech entrepreneurs, died the morning of Aug. 4. He was 76.

Tachi Yamada

Yamada died from a heart attack while exercising at home in Seattle, said his son, Takao.

“He was a special person who did things to help people. That was his North Star,” his son said.

Yamada was a rare leader with experience in several dimensions of the scientific enterprise – academia, industry, and philanthropy. He was best known for high-profile roles later in his career as the chairman of R&D at GSK, the president of the $9 billion global health program at the Bill & Melinda Gates Foundation, and then as chief medical and scientific officer at Takeda Pharmaceuticals.

Those jobs came after Yamada made an early mark as a physician-scientist, specializing as a professor of gastroenterology at UCLA and then at the University of Michigan. He was elected by peers to National Academy of Medicine in 1994, around the time he made the move to the pharmaceutical industry.

Over the past 25 years, Yamada accomplished a series of things that will last. He built up GSK’s vaccine business to combat rotavirus and shingles and other infectious diseases. He further invested in vaccines at Takeda, including vaccines for dengue and norovirus. He helped transform Takeda from a regional pharmaceutical company into a top-tier global pharma R&D enterprise, serving as an important champion of vedolizumab (Entyvio) for Crohn’s and ulcerative colitis — a blockbuster product.

More recently, as an advisor to small companies, Yamada helped launch the Philadelphia-based gene therapy company Passage Bio with longtime friend and colleague Jim Wilson of the University of Pennsylvania, as well as Florham Park, NJ-based Phathom Pharmaceuticals, a developer of gastrointestinal drugs.

Many colleagues were shocked and in mourning over the death of such a healthy and vibrant man.

Andy Plump, president of R&D, Takeda Pharmaceutical

“He was the embodiment of life,” said Andy Plump, the president of R&D at Takeda who took over when Yamada left in 2015. “He took care of himself. Ate well. Exercised, literally every day.”

As a business leader, Yamada “was really, really smart. Very sharp. Extremely experienced,” Plump said. “He was tough. He had a vision and was not shy around that vision and really driving something he believed in.”

“I’m heartbroken,” said Thong Le, the CEO of Accelerator Life Science Partners in Seattle, who recruited Yamada to join his board of directors seven years ago. “It wasn’t his time. He was still doing so many great things…no matter how complicated the situation, he got to the nub and knew what needed to be done. He’s one of those few guys with a unique mix of understanding the medical need and all the business and technology challenges that go with developing a new treatment.”

Thong Le, CEO, Accelerator Life Science Partners

Bruce Goldsmith, the CEO of Philadelphia-based Passage Bio, a gene therapy company where Yamada was chairman of the board, was in grief.

“He put a lot of faith in me as a first-time CEO. He always gave me the support I needed to work independently, to build the company independently, but that wouldn’t mean he wouldn’t give me critical comments to think about…once he decided to invest in a person…I saw a massive amount of commitment from him. When there was uncertainty, questions as there always are, he’d set aside time constantly to make sure we’d figure it out.”

Yamada’s life journey started in Japan. He was born in Tokyo on June 5, 1945, just before the end of World War II. He moved to the United States as a boy and attended Phillips Academy in Andover, Mass. before going to Stanford University, where he majored in history.

After getting his medical degree at New York University, he did his internship and residency in Richmond, Virginia, followed by a three-year stint as a major specializing in infectious diseases at the US Army Medical Research Institute of Infectious Diseases. He spent the next 20 years as an academic gastroenterologist, starting at UCLA and then building one of the nation’s leading departments at the University of Michigan.

He sought new opportunity to help patients through industry at SmithKline Beecham in 1994, starting in a non-executive director position. He quickly worked his way up, ultimately overseeing one of the industry’s major R&D engines at GSK in the early 2000s, following a megamerger with Glaxo Wellcome.

Yamada saw a new opportunity in 2006 to take over the global health program at the Bill & Melinda Gates Foundation. The world’s largest private philanthropy was ascendant on the global stage, flush with cash from Warren Buffett, and in position influence global health priorities around fighting tuberculosis, malaria and HIV. He stayed five years before moving back to industry.

At Takeda, Yamada was able to use his accumulated experience to help position the company to make a bigger global impact.

At the time, Takeda was fragmented across four organizations – Takeda Japan, the TAP Pharmaceuticals joint venture between Takeda and Abbott, the Millennium Pharmaceuticals team in Cambridge, Mass., and Nycomed in Europe. “He started a process, a fairly challenging process, of consolidating activities,” Plump said.

Yamada worked closely with then-Takeda CEO Yasuo Hasegawa to bring the far-flung operations together, implement more disciplined decision-making processes, and step up its game in science, Plump said.

When Hasegawa stepped aside and Christophe Weber came in as the first non-Japanese CEO of the 200-year-old company, Yamada, about 70 at the time, played an important role in keeping the transition on track until it was time for Weber to bring in a new R&D chief he could work with for the next decade. “Tachi bridged between them [Hasegawa and Weber] and lit the flames of cultural change in R&D,” Plump said.

“Few people can lead in so many different capacities as he did — in academia, in the NGO world at the highest level, and two times in pharma at the highest level in R&D,” Plump said.

The last chapter of Yamada’s career was a whirlwind. He served as chairman of the board at Phathom Pharmaceuticals, Passage Bio, and Athira Pharma. He served on the boards of a number of other small companies, partly through his relationship with Frazier Healthcare Partners.

The Frazier relationship provided an avenue for him to help a number of entrepreneurs across disciplines. The work there dated back to his time at the Gates Foundation. He stepped away from Frazier during his time at Takeda to avoid conflicts, and then returned as a venture partner in 2015.

It was an opportunity to paint on a broader canvas across the startup community, and to pick the people and projects he felt passionate about.

A day after the announcement that he was leaving Takeda, Le happened to have a pre-scheduled meeting. He walked in and got straight to the point. “Hey, I saw the announcement, and I’m sure 100 people will ask you the same thing. But I need your help,” Le said.

He asked Yamada to join his board.

“He chuckled, like he always does,” Le recalled.

Then came an unequivocal answer.

I haven’t figured out what to do with my time, Yamada told Le, “but I believe in you. Of course, I’m going to help you.”

Le was a bit choked up re-telling the story, knowing how many doors Yamada opened, and how much his committed counsel helped keep things moving forward for Accelerator. “I feel like I’ve lost a mentor, and almost like I’ve lost a father,” Le said.

Yamada, for instance, played a key behind-the-scenes role in Accelerator’s successful sale of Rodeo Therapeutics to Amgen earlier this year. (TR coverage, Mar. 2021).

Jamie Topper, managing partner, Frazier Healthcare Partners

Jamie Topper, managing partner at Frazier, said the firm was eager to have Yamada re-engage the last six years. Phathom and Passage are a couple of the portfolio companies that he helped ignite.

“Tachi is a polymath. As far as I can tell, he worked 22 hours a day, 7 days a week,” Topper said. “When he was looking at an area, he read widely in that area. He would know everything from the basic science to the clinical relevance. He lived and breathed medicine his entire career. He was a man of breadth and depth. He brought a compassion for patients and the families of the patients.”

Stylistically, Yamada was poised. He could come across as mild-mannered and soft-spoken. A man who would choose his words carefully, and speak succinctly.

“One of my favorite things about Tachi is that he was always very direct. He would do it in a polite and respectful way. If he disagreed with you about something, he could disagree and it would remain civil,” Topper said.

Le, of Accelerator, spoke of that same directness. Yamada would listen carefully and absorb information. He would also suffer no fools. “He could cut the BS and get right to whatever was most important,” Le said. “It’s such an important skill in today’s world with so much information. Knowing what to focus on can mean the difference between success and failure.”

Goldsmith of Passage Bio said he was struck by a certain agility of mind.

“You can have these big strategic overarching vision conversations with him, and then these really detailed operational conversations. He could back and forth, and it was his experience that enabled him to go back and forth. We could talk about where we should go and how to get there,” Goldsmith said.

Bruce Goldsmith, CEO, Passage Bio

Not every polymath is known for personal warmth, but those who know Yamada said he radiated that, too.

Le said that when having a meeting, Yamada would often invite him to come sit down on a couch beside him, instead of from an imposing chair behind a desk.

Goldsmith said Yamada once told him, as the senior person in the company, it’s good to always show up 1-2 minutes purposely late for a meeting so that no one on the team would feel bad for showing up late and potentially irritating the boss. It was a subtlety, but it worked, Goldsmith said.

Plump recalls traveling to Japan and waking up at the hotel, jet-lagged, and heading down to the gym at some odd hour like 3 am or 4 am or 5 am. Always, he’d see Yamada already there doing his workout. Over 30 years, Yamada told him, he’d taken two days off from his physical fitness routine.

Yamada’s favorite drink was always an ice-cold green tea. It helped him stay fresh and energized for the work. He avoided alcohol. Those consistent, disciplined habits — of body and mind — were part of what made Yamada successful. Among the many bits of advice he gave his successor, Plump remembers the part about not getting worn out. “Take care of yourself,” Yamada said. “Because the things you’re going to have to do will be stressful at times.”

Another key piece of advice from Yamada: “Everyone you work with will have something positive to offer. You need to find out what that is, and position them best so they can provide that.”

The two men had many dinner meetings during the transition at Takeda, and Yamada enjoyed discussing his family and introducing them. Goldsmith noticed the same thing – no matter how focused or intense a meeting might have been, Yamada had time at the end to talk about life, family, what was new and interesting.

Plump shared one last story. Once, when he was stuck in traffic and running 30 minutes late for a meeting with Yamada, he felt terrible and apologized profusely upon arrival.

Yamada, the picture of discipline and poise, shrugged it off, and told him not to worry. Yamada had spent the time with four different newspapers open in front of him, absorbing information from different sources and perspectives.

Plump took note. There was a scientific executive always seeking to learn, always seeking to understand, always synthesizing different perspectives. A man on a quest to get to the heart of the matter, and to advance human health.

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