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Dr. Yvonne Burkart is a board-certified toxicologist with over 15 years of experience specializing in environmental health, chemical safety, and human health risk assessment.

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Feng Zhang, a professor of neuroscience at MIT and a pioneering figure in gene editing, joins Peter to discuss his groundbreaking work in CRISPR technology, as well as his early contributions to optogenetics. In this episode, they explore the origins of CRISPR and the revolutionary advancements that have transformed the field of gene editing. Feng delves into the practical applications of CRISPR for treating genetic diseases, the importance of delivery methods, and the current successes and challenges in targeting cells specific tissues such as those in the liver and eye. He also covers the ethical implications of gene editing, including the debate around germline modification, as well as reflections on Feng’s personal journey, the impact of mentorship, and the future potential of genetic medicine.

We discuss:

• Feng’s background, experience in developing optogenetics, and his shift toward improving gene-editing technologies [2:45];
• The discovery of CRISPR in bacterial DNA and the realization that these sequences could be harnessed for gene editing [10:45];
• How the CRISPR system fights off viral infections and the role of the Cas9 enzyme and PAM sequence [21:00];
• The limitations of earlier gene-editing technologies prior to CRISPR [28:15];
• How CRISPR revolutionized the field of gene editing, potential applications, and ongoing challenges [36:45];
• CRISPR’s potential in treating genetic diseases and the challenges of effective delivery [48:00];
• How CRISPR is used to treat sickle cell anemia [53:15];
• Gene editing with base editing, the role of AI in protein engineering, and challenges of delivery to the right cells [1:00:15];
• How CRISPR is advancing scientific research by fast-tracking the development of transgenic mice [1:06:45];
• Advantages of Cas13’s ability to direct CRISPR to cleave RNA and the advances and remaining challenges of delivery [1:11:00];
• CRISPR-Cas9: therapeutic applications in the liver and the eye [1:19:45];
• The ethical implications of gene editing, the debate around germline modification, regulation, and more [1:30:45];
• Genetic engineering to enhance human traits: challenges, trade-offs, and ethical concerns [1:40:45];
• Feng’s early life, the influence of the American education system, and the critical role teachers played in shaping his desire to explore gene-editing technology [1:46:00];
• Feng’s optimism about the trajectory of science [1:58:15]; and
• More.

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• Now more than ever,young men are uncertain about what the world needs from them
• The increase in young male suicide may be due to men retreating from the difficulties and challenges of modern society 
• “The state of feeling unneeded is literally fatal.” – Richard Reeves 
• Four out of five teens who commit suicide are boys: Across every age group, the suicide rate is 4x higher amongst men than women 
• There has been an expansion in the domains of neediness for women and a contraction in the domain of neediness for men 
• The mental health field is more female-friendly than male-friendly; the whole field of mental health has been coded as female and feminine – and we wonder why men are not interested in it!  
• Young men feel politically homeless, and they especially do not feel welcomed by the political left; instead of turning to the left or the right, younger men tend to retreat 
• Recently, there has been a massive increase in drug poisoning deaths among young men

• From 2001 to today in the United States, the increase in deaths from drug poisoning is equivalent to an additional 400,000 men

Richard Reeves is a writer, researcher and the Founder of the American Institute for Boys & Men.

• “If Steve Jobs studied Edwin Land, I think every other founder should as well.” – David Senra 
• Optimize for breadth as well as depth; hire the chemist who does photography on the side! 
• Something magical exists at the intersection of the humanities and the sciences 
• “Missionaries make better products.” – Jeff Bezos 
  • Missionaries and mercenaries are the two types of people that will be attracted to a company
  • While the mercenaries are there for the perks, status, and money, the missionaries are there to make better products because they believe in what the company is doing
• Leverage the power of demonstration: No argument in the world can compare with one dramatic demonstration
• A first-class product needs first-class packaging and marketing! 
• The founder is the guardian of the company’s soul 
• If you are lucky enough to find your life’s work, why would you quit? 
• You should take yourself seriously, but don’t make yourself miserable; none of us get out of this alive 

What I learned from rereading Instant: The Story of Polaroid by Christopher Bonanos. 

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Episode Outline: 

— The most obvious parallel is to Apple Computer. Both companies specialized in relentless, obsessive refinement of their technologies. Both were established close to great research universities to attract talent. Both fetishized superior, elegant, covetable product design. And both companies exploded in size and wealth under an in-house visionary-godhead-inventor-genius. At Apple, that man was Steve Jobs. At Polaroid, the genius was Edwin Land. Just as Apple stories almost all lead back to Jobs, Polaroid lore always seems to focus on Land.

— Both men were college dropouts; both became as rich as anyone could ever wish to be; and both insisted that their inventions would change the fundamental nature of human interaction.

— Jobs expressed his deep admiration for Edwin Land. He called him a national treasure.

— Books on Edwin Land:

Land's Polaroid: A Company and the Man Who Invented It by Peter C. Wensberg (Founders #263)

A Triumph of Genius: Edwin Land, Polaroid, and the Kodak Patent War by Ronald Fierstein (Founders #134)

Land's Polaroid: A Company and the Man Who Invented It by Peter C. Wensberg (Founders #133)

The Instant Image: Edwin Land and the Polaroid Experience by Mark Olshaker (Founders #132)

Insisting On The Impossible: The Life of Edwin Land and Instant: The Story of Polaroid(Founders #40)

— Biography about Steve Jobs: Becoming Steve Jobs: The Evolution of a Reckless Upstart into a Visionary Leader by Brent Schlender and Rick Tetzeli

— Edwin Land of Polaroid talked about the intersection of the humanities and science. I like that intersection. There's something magical about that place. There are a lot of people innovating, and that's not the main distinction of my career. The reason Apple resonates with people is that there's a deep current of humanity in our innovation. I think great artists and great engineers are similar, in that they both have a  desire to express themselves. In fact some of the best people working on the original Mac were poets and musicians on the side. In the seventies computers became a way for people to express their creativity. Great artists like Leonardo da Vinci and Michelangelo were also great at science. Michelangelo knew a lot about how to quarry stone, not just how to be a sculptor. —  Steve Jobs: The Exclusive Biography by Walter Isaacson (Founders #214)

— Book on Henry Ford:

I Invented the Modern Age: The Rise of Henry Ford by Richard Snow (Founders #9)

The Autobiography of Henry Ford by Henry Ford (Founders #26) 

Today and Tomorrow Henry Ford (Founders #80) 

My Forty Years With Ford by Charles Sorensen  (Founders #118)

The Story of Henry Ford and Thomas Edison's Ten Year Road Trip by Jeff Guinn (Founders #190) 

— Another parallel to Jobs: Land's control over his company was nearly absolute, and he exercised it to a degree that was compelling and sometimes exhausting.

— When you read a biography of Edwin land you see an incredibly smart, gifted, driven, focused person endure decade after decade of struggle. And more importantly —finally work his way through.

— Another parallel to Jobs: You may be noticing that none of this has anything to do with instant photography. Polarizers rather than pictures would define the first two decades of lands intellectual life and would establish his company. Instant photos were an idea that came later on, a secondary business around which his company was completely recreated.

— “Missionaries make better products.” —Jeff Bezos

— His letter to shareholders gradually became a particularly dramatic showcase for his language and his thinking. These letters-really more like personal mission statements-are thoughtful and compact, and just eccentric enough to be completely engaging. Instead of discussing earnings and growth they laid out Land's World inviting everyone to join.

— Land gave him a four-word job description: "Keeper of the language.”

— No argument in the world can ever compare with one dramatic demonstration. — My Life in Advertising by Claude Hopkins (Founders #170)

— The leap to Polaroid was like replacing a messenger on horseback with your first telephone.

— Hire a paid critic:

Norio Ohga, who had been a vocal arts student at the Tokyo University of Arts when he saw our first audio tape recorder back in 1950. I had had my eye on him for all those years because of his bold criticism of our first machine.

He was a great champion of the tape recorder, but he was severe with us because he didn't think our early machine was good enough. It had too much wow and flutter, he said. He was right, of course; our first machine was rather primitive. We invited him to be a paid critic even while he was still in school. His ideas were very challenging. He said then, "A ballet dancer needs a mirror to perfect her style, her technique.

— Made in Japan: Akio Morita and Sony by Akio Morita.

— Another parallel to Jobs: Don't kid yourself. Polaroid is a one man company.

— He argued there was no reason that well-designed, wellmade computers couldn't command the same market share and margins as a luxury automobile.

A BMW might get you to where you are going in the same way as a Chevy that costs half the price, but there will always be those who will pay for the better ride in the sexier car. Rather than competing with commodity PC makers like Dell, Compaq and Gateway, why not make only first-class products with high margins so that Apple could continue to develop even better first-class products?

The company could make much bigger profits from selling a $3,000 machine rather than a $500 machine, even if they sold fewer of them.

Why not, then, just concentrate on making the best $3,000 machines around? — Jony Ive: The Genius Behind Apple's Greatest Products by Leander Kahney.

— How To Turn Down A Billion Dollars: The Snapchat Story by Billy Gallagher 

— Books on Enzo Ferrari

Go Like Hell: Ford, Ferrari, and Their Battle for Speed and Glory at Le Mans by A.J. Baime. (Founders #97) 

Enzo Ferrari: Power, Politics, and The Making of an Automotive Empire by Luca Dal Monte (Founders #98) 

Enzo Ferrari: The Man and The Machine by Brock Yates (Founders #220) 

— Soul in the game. Listen to how Edwin Land describes his product:

We would not have known and have only just learned that a new kind of relationship between people in groups is brought into being by SX-70 when the members of a group are photographing and being photographed and sharing the photographs: it turns out that buried within us—

there is latent interest in each other; there is tenderness, curiosity, excitement, affection, companionability and humor; it turns out, in this cold world where man grows distant from man,

and even lovers can reach each other only briefly, that we have a yen for and a primordial competence for a quiet good-humored delight in each other:

we have a prehistoric tribal competence for a non-physical, non-emotional, non-sexual satisfaction in being partners in the lonely exploration of a once empty planet.

—  “Over the very long term, history shows that the chances of any business surviving in a manner agreeable to a company’s owners are slim at best.” —Charlie Munger

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• In medicine (and everywhere), there is resistance to new ideas – so many people have spent so much time holding a certain belief, that the cost is too high to change
• The distrust in science and medicine is because there is no humility in walking back incorrect information
• We need people who are willing to speak up instead of falling in line; science is the study of challenging deeply held assumptions
• We need new frontiers of medicine, people are hungry for answers
• The future of medicine is hopeful as the new generation of medical students and doctors is not on board with the traditional path of doing whatever you need to secure NIH funding and falling in line

• It’s time we consider NIH term limits
• We spend more money on pharmaceuticals than we do on understanding the origins of disease

Marty Makary, MD is a Johns Hopkins professor and member of the National Academy of Medicine. He is the author of Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health.

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• Check out the episode page

The Learning Leader Show With Ryan Hawk

Full show notes at www.LearningLeader.com

My books:

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Seth Godin is the author of 21 international bestsellers that have changed the way people think about work and art. They have been translated into 38 languages. His breakthrough books include Purple Cow, Tribes, The Dip, Linchpin, and his latest book is called This is Strategy. He writes one of the most popular daily blogs in the world and has given 5 TED talks. He is the founder of the altMBA, and the former VP of Direct Marketing at Yahoo!

Notes:

• "If you want word of mouth, you have to create something remarkable, and that means it’s worthy of remark."
• The elegant path is the most useful way forward. “My neighbor is a barefoot runner. He glides without apparent effort.” Elegance is simplicity, efficiency, and effectiveness.
• Dorothy and Her Crew. How did Dorothy persuade the Lion, Tin Man, and Scarecrow to join her on the trip to see the Wizard? Did she make a case about how much she missed home? No. She created the conditions where the others could get what they wanted by joining her.
• Seeing Strategy Clearly. Strategy is a flexible plan that guides us as we seek to create a change. It helps us make decisions over time while working within a system.
• Low-Hanging Fruit Isn’t. It’s all been picked. The easy, direct, obvious paths are unlikely to get you the results you’re working so hard to obtain. In fact, these paths are probably a trap.
• Seth, at one point, got 800 rejection letters. Have to keep going...
• "I wouldn't call Steve Ballmer a good leader."
• An example of Seth making a difference... He went to Kenya and talked with 60 people who started a book club based on his book Linchpin. "They decided to be leaders."
• Make decisions in the moment:
  • Examine the issue
  • Get feedback
  • Look for patterns
• "Taste is knowing what the market wants before it knows it."
• Rick Rubin
  • Reality distortion field
  • Johnny Cash
  • "What do you think?"
• "Objections are your friends."
• What are the commonalities among leaders with whom Seth has worked and who have sustained excellence? They are all different, but the one thing they have in common is they all have chosen to be leaders. And that means that they are here to make a change happen.
• Management doesn’t just exist. It was invented. When you race to the bottom, You see people as resources, not as people.
• Questions That Lead To Strategies. 84 questions. They’ll force you to think through your strategy. By answering them, you’ll be better prepared to make a difference… And make a ruckus. Some of them: Who is this project for? What is my timeline? What systems would need to change for my project to succeed? Where will I cause tension? What resistance should I anticipate? Where is the empathy? What asset would transform my project? What can I learn from comparable projects? Is the change I’m making contagious? Can I make it easier for others to decide? How can I design for network effects? What are common objections I expect to encounter?