A Few Things: Life's Cheat Codes, AI Copilot For Finance, Top 10 Lessons from Rockefeller, America's Immigration, Nuclear Energy, The Longevity Imperative, ARK's BIG Ideas, Century Of Biology....
February 1, 2024
I am sharing this weekly email with you because I count you in the group of people I learn from and enjoy being around.
Here is last week’s discussion: The Retail Rally, The Other Bull Market, The Gender Divide, 49 Changes For Healthier Happier Life, Rory Sutherland, Quantum Computing, News & Charts You Might Have Missed....
Today’s email goes from low density to high density from top to bottom.
Quotes I Am Thinking About:
“Where is the Life we have lost in living? Where is the wisdom we have lost in knowledge? Where is the knowledge we have lost in information?”
- T.S. Eliot
“There is no education like adversity.”
- Benjamin Disraeli
“Rolex watches are sold to people who climb mountains. Patek Philippe watches are sold to people who own mountains.”
- Patek Philippe
“If you really want to do something, you’ll find a way. If you don’t, you’ll find an excuse.”
- Jim Rohn
“Don’t aim at success—the more you aim at it and make it a target, the more you are going to miss it. For success, like happiness, cannot be pursued; it must ensue, and it only does so as the unintended side-effect of one’s dedication…In the long run—in the long run, I say!—success will follow you precisely because you had forgotten to think about it.”
- Viktor Frankl
A. A Few Things Worth Checking Out:
2. This is a cool AI Copilot for Finance. I’ve been using it. Thank you Tamas V.
3. How to Have Meetings That Don't Suck by NZS Capital.
Three Key Ideas:
Foster an environment of trust and psychological safety. This allows for open debate, willingness to change minds, and checking egos/biases at the door.
Expect and require preparedness from all participants. This levels the playing field and prevents one person from dominating or railroading the discussion.
Debate ideas, not people. Focus criticism on the idea or argument, not the person making it. This enables constructive back-and-forth without things getting personal.
The overall emphasis is on creating a collaborative, ego-free environment where the focus is on constructive problem-solving rather than politics, posturing, or protecting territories. This leads to better ideas and decisions emerging from the wisdom of the group.
4. David Senra’s Top 10 lessons from John. D. Rockefeller’s Letters to his son.
5. The Economist had a cover story titled: America’s immigration policies are failing and why Immigration might cost Biden the election.
5 Key Insights:
There has been a major surge in migrants crossing the southern border illegally, with nearly 250,000 apprehended in November 2023. This is perceived as a political liability for President Biden.
Multiple factors explain the surge, including violence and instability globally, abundant US job openings, the perception that Biden is more welcoming than Trump, and cumbersome legal pathways to enter.
Decades of neglect and partisan conflict have crippled the US immigration system. Congress has not passed meaningful reform since 1990.
Biden has tried to steer migrants to ports of entry and use smartphone apps for appointments, but most still cross illegally and request asylum. A backlog of over 3 million cases means extremely long waits.
With the 2024 election looming, Biden wants to strike a deal with Congress to fund border enforcement and limit asylum in exchange for Ukraine aid. But agreement faces obstacles from both parties. Voters seem to favor such a compromise bill.
Harris Kupperman at Praetorian Capital was on the Going Nuclear podcast discussing the latest and BCA published this 13-page primer on Nuclear Energy.
Disclosure: I am long various Uranium related assets and businesses.
B. The Longevity Imperative
Professor Andrew Scott is one of my favourite people and thinkers.
His new book “The Longevity Imperative” compellingly argues for a comprehensive societal transformation in response to increasing life expectancies. You may have read his prior books, including: The 100-Year Life and The New Long Life.
Professor Scott articulates a vision for a “longevity society,” where longer lives are not seen as a burden but as an opportunity for growth, innovation, and sustainability. He presents the "longevity imperative" as an urgent need for systemic change across healthcare, employment, education, and financial planning to ensure that an aging population can lead fulfilling, healthy, and secure lives.
Niall Ferguson, Milbank Family Senior Fellow, the Hoover Institution, Stanford says:
As improvements in medical science and living standards ensure that most of us now live to be old, how do we make sure that we "age well"—that we are "evergreen"? That is the question at the heart of Andrew Scott's striking new book, which argues persuasively that aging is as big a challenge for humanity as climate change or artificial intelligence...
Scott has some wise suggestions as to how exactly we can do it.
David Sinclair, Professor of Genetics, Harvard Medical School, author of NYT Bestseller “Lifespan” says:
Finally, a manifesto to guide the longevity revolution. A revelation on every page. Should be required reading for every physician and politician. On almost every page, I found myself saying, ‘Really, I didn’t know that!’
Key insights from his book:
Healthcare Transformation: Advocating for a shift towards preventative care to manage health across longer lifespans.
Rethinking Work and Education: Adapting these systems for continuous growth and flexibility, rather than a linear progression from education to retirement.
Innovative Financial Products: Developing new financial strategies to support extended lifetimes.
Cultural Shift in Aging Perception: Promoting a positive, proactive approach to aging, recognising the potential for contribution and growth at all ages.
The book proposes practical strategies for individuals and societies to invest in future well-being and longevity. These include focusing on preventative health measures, enhancing public health infrastructure, fostering personal and social development throughout life, and building and maintaining strong relationships. He also calls for a "health revolution" that prioritizes maintaining good health through an integrated approach that considers environmental, occupational, and lifestyle factors.
“The Longevity Imperative” is not just a call to action but a roadmap for navigating the complexities of an aging global population. It underscores the need for a paradigm shift in how we view and prepare for longer lifespans, advocating for policies and practices that support a healthy, engaged, and financially secure aging population. His work encourages a reevaluation of our societal structures to embrace the longevity dividend, ultimately fostering a world where aging is not feared but celebrated as an opportunity for continued growth and contribution.
Many of you are interested in Longevity and it’s myriad impacts and opportunities, I will be hosting a very special zoom session with Prof. Scott on March 20th 12 pm EST (just a week after the book is released) to discuss the Longevity Imperative.
We will limit the party to 40 people to make sure we can have an open and interactive discussion. If you’d like me to hold you a precious spot, just reply to lock it in.
C. The Science and Technology Section
1. ARK Invest shared their Annual BIG IDEAS 2024 Research Report.
2. Could cells replace pills as the most ubiquitous form of medicine? Elliot Hershberg at The Century of Biology had a new essay on the past, present, and future of cell-based therapy.
Three Key Insights:
Engineered cell therapies like CAR-T represent a completely new paradigm for medicine where cells are genetically programmed to detect and treat disease when introduced into the body. CAR-T has shown extraordinarily promising results, with 83% of patients in remission within 3 months in one trial.
There is currently a major bottleneck in manufacturing cell therapies at scale to meet patient demand. Startups are proposing futuristic solutions like cellular "factories in a box" and microfluidic chips that manufacture therapies at a patient's bedside. Solving this could enable cell therapies to transform medicine.
Cell therapies have potential far beyond engineered immune cells for cancer. Induced pluripotent stem cells could enable organ regeneration, reprogramming cells could reverse aging, and engineered gut microbes could treat diseases by secreting therapeutic compounds. If realized, cells could become medicine's "endgame" for delivering small and large molecule drugs.
3. Invest Like The Best recent episode titled: Unlocking Innovation in Pharma had Alex Telford, founder of Convoke.
They discussed the pharmaceutical industry, including the drug development process, areas of innovation, regulation and clinical trials, profits and pricing, and reasons for optimism and concern about the future.
Drug development starts with academic research to understand disease mechanisms, then biotech/pharma companies develop molecules to target disease pathways and test them through preclinical and clinical trials before seeking regulatory approval. The process typically takes 10-15 years.
Major innovation areas that will impact the next 10-20 years include gene therapies, cell therapies like CAR-T, and radiopharmaceuticals. The key is streamlining complex manufacturing and delivery processes to make them scalable.
Regulation balances safety and speed of access. AIDS crisis led to accelerated approval for high unmet need areas, but overall process innovation is slow (Eroom's law). Surrogate markers of efficacy can speed up trials.
Blockbuster drugs drive industry revenue through extreme financial returns that compensate for many failed drugs. U.S. prices subsidize global market but strain system. Prevention under-invested in partly due to patient/payer demand.
Reasons for optimism include explosion of versatile new treatment platforms like CRISPR gene editing. Reasons for concern include reduced investment in innovative R&D if commercial pressures dominate scientific vision.
4. If you want to go deeper Alex Telford also wrote a detailed blog post titled: Why drugs got harder to develop and what we can do about it.
Key ideas in the deep blog post:
In the past, drug discovery was faster and less regulated. You could rapidly test compounds in patients with minimal oversight. Today's extensive regulations, while important for safety, slow down the process.
The cost to develop a new drug has skyrocketed, from $40 million to $2.5 billion today (adjusted for inflation). Clinical trials in particular have become larger, more complex, and more expensive to run. As a result, pharmaceutical R&D productivity has declined over the past decades, with fewer new drugs approved per billion dollars spent. This downward trend is known as "Eroom's law."
Reasons for declining productivity include: competition from existing effective treatments, complexity of biology and diseases tackled, rising regulatory requirements, and duplication of efforts across the industry.
Recent productivity gains with biologics like antibodies and early successes with gene therapies provide some optimism. Further policy changes to reduce regulatory burdens could also boost efficiency.
Ultimately we need to find ways to make experimentation cheaper again to recapture rapid, serendipitous discoveries. This will require changes in policy, regulation, clinical trials, and potentially new technologies or business models.
5. I believe that the next few decades if not century could be about biology as we go deeper into the human body and use technology to better understand the world inside us, just as we have spent the last century exploring the world outside and around us.
To learn the language of biology I have been taking this MIT course online (thank you Leila Z for recommending).
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