The Long Game 29: Continuous Cortisol Monitoring, Psychedelics and Religion, Different Identities, Malignant

🚑 The US Healthcare System, A New Idea of India, The Manager's Handbook, Mars in Color, and Much More!

Hi there,

Greetings from Montenegro 🇲🇪

If you missed the past episodes, you could catch up here.

In this episode, we explore:

  • Continuous cortisol monitoring

  • Different identities

  • A hypothesis is a liability

  • The Manager’s Handbook

  • Malignant

  • A New Idea of India

Let’s dive in!

Nina Kraviz — Cyberpunk 2077


🥑 Health

💉 Continuous Cortisol Monitoring

As you may know by now, I’m working on bringing continuous glucose monitoring to the mainstream at lifetizr.

This week, I discussed Cortisol with a friend and how stress levels fluctuate throughout the days. We imagined that having a continuous measure of cortisol in real-time could be very helpful for many people.

Later on, I did some research and found this paper about continuous cortisol monitoring. Here’s the abstract:

Accumulating evidence supports the harmful effects of stress on health, including the development and progress of psychopathology (e.g. anxiety disorders), metabolic disorders (e.g. diabetes type II), inflammatory disturbances, and cardiovascular disease. These harmful effects are often expressed as disturbances in cortisol levels, patterns, or responses. Unfortunately, at present, cortisol assessment is only performed in the laboratory. This hinders rapid quantification, let alone being determined by individuals themselves, with self-testing devices or sensors. More accurate and timely detection of cortisol may have important implications for the prevention, diagnosis, and treatment of stress-related disorders as well as for those suffering from adrenal insufficiencies. The present review provides an overview of the most promising and challenging technologies for cortisol measurement. An important first conclusion might be that almost all reviewed technologies were at the proof-of-concept stage, meaning it was premature to interpret the findings in light of regulatory requirements for in vitro diagnostics. Nevertheless, several promising proto-types, including electrochemical sensors with wearable potential, were found and are consequently discussed. Overall the findings suggest that with significant additional investments and research efforts in the coming years, accurate, rapid, and repeated cortisol assessment in everyday life can become reality.

The future of health will be to get feedback on what’s going wrong in our body as soon as possible. Bio-sensors will play a major role here. We’re only at the beginning of a new era that will enable new possibilities for our health and longevity.

I’m very excited to be working on it at lifetizr. If you’re curious about continuous blood glucose monitoring, sign up for early access!

Get early access

Here’s a similar idea, but with dopamine 👇


🌱 Wellness

👥 Different Identities

Identity is something I’ve been thinking about a lot lately. Can I change some parts of my identity? Which ones? Is it malleable or set in stone? Who am I?

I believe these questions are essential because they’ll determine so much in your life and your wellbeing. What led me to this topic was this short clip from Lex Fridman’s podcast with Lisa Feldman Barrett. They discuss the classic and very confusing “Just Be Yourself” advice.

What does “being yourself” mean? How much should you push in some directions to get better, for example?

A lot of who you can eventually become is determined by the self-talk you have about yourself. For example, if you were lazier than the norm for a large part of your life, holding this belief about yourself will be a major hurdle in achieving anything meaningful.

Behavioral geneticists will argue that most of who we are is written in our genes, but they still accept that there’s a huge margin in what each one of us can achieve with his own genome.

The question now is whether it’s possible to change your identity and personality and how flexible someone’s “true” self is. Scott Barry Kaufman wrote a piece on this exact topic, and he concludes:

The first step to making real, lasting personality adjustments, then, it seems, is to be critical of any self-development program that touts instant, or even radical, change. Just as it takes many years to develop patterns of thoughts, feelings, and behaviors, it will take some time—perhaps many years—to alter them. But the good news is that changeis possible.

It’s possible to change, but it takes time. Seth Godin has a great way to articulate how to do this change. He explains that authenticity is overrated; we shouldn’t care so much about how we feel at the moment. We should just do what we said we’re going to do—one day after the other. What matters is consistency and reliability.


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🧠 Better Thinking

🔬 A Hypothesis is a Liability

“ ‘When someone seeks,’ said Siddhartha, ‘then it easily happens that his eyes see only the thing that he seeks, and he is able to find nothing, to take in nothing. [...] Seeking means: having a goal. But finding means: being free, being open, having no goal.’ ” Hermann Hesse

I found this paper extremely interesting (h/t to Alex Danco for sharing it); here’s the abstract:

There is a hidden cost to having a hypothesis. It arises from the relationship between night science and day science, the two very distinct modes of activity in which scientific ideas are generated and tested, respectively. With a hypothesis in hand, the impressive strengths of day science are unleashed, guiding us in designing tests, estimating parameters, and throwing out the hypothesis if it fails the tests. But when we analyze the results of an experiment, our mental focus on a specific hypothesis can prevent us from exploring other aspects of the data, effectively blinding us to new ideas. A hypothesis then becomes a liability for any night science explorations. The corresponding limitations on our creativity, self-imposed in hypothesis-driven research, are of particular concern in the context of modern biological datasets, which are often vast and likely to contain hints at multiple distinct and potentially exciting discoveries. Night science has its own liability though, generating many spurious relationships and false hypotheses. Fortunately, these are exposed by the light of day science, emphasizing the complementarity of the two modes, where each overcomes the other’s shortcomings.

More than just confirmation bias, we can easily forget the bigger picture when we hold a hypothesis about a question. If you’re looking to find out whether it’s option A or option B that’s correct, you might miss that there are also options C, D, E, or that this question doesn’t even matter in the first place.


⚡️ Startup Stuff

📖 The Manager’s Handbook

This handbook by Alex MacCaw is a goldmine. It contains everything you know to become a great manager.

Here’s a short highlight on how to manage your time and calendar:

The first rule in time management is to ruthlessly protect your time. In a world of abundance, your time is the most limited resource. Do not let anyone else create events on your calendar. It should be jealously guarded.

Whenever someone asks for your time, instead of accepting a meeting, ask whether their issue could be resolved with a Slack message, Google Doc, or email instead. If a meeting is inevitable, keep it as short as possible. Ensure that everyone is prepared for the meeting in order to make the most out of the time, and stack your meetings on specific days to ensure long periods of uninterrupted time outside those days where you can get focused work done.

What’s the time management practice that had the most impact on your productivity? Let me know!


📚 What I Read

💊 Malignant: How Bad Policy and Bad Evidence Harm People with Cancer

After reading about the US healthcare system and understanding how bad it is, it was time for me to switch to a different topic—cancer—and understand the problems of oncology.

Malignant by Vinayak K. Prasad didn’t disappoint, and let me give you a spoiler; the problems are almost as catastrophic as in the healthcare system.

I would highly recommend this book to anyone curious about the field and curious about what good science is.

Here are a few noteworthy highlights I got from the book:

  • Surrogate endpoints often fail to assess whether there is an increased survival rate.

  • Depending on the radiologist & endocrinologist, you get a different measure of tumor growth.

  • Med Twitter: there are a lot of conflicts of interest, doctors not disclosing their ties with pharma, and that’s a big problem because Twitter sets the tone for the whole field.

  • There’s a revolving door between FDA & Big Pharma.

  • One day genetic sequencing will be the solution for precision treatments, but this day is not today.

  • We need Randomized Control Trials, and we need to stop approving extremely costly drugs that do not significantly impact the quality of life of patients.

Here are the 6 rules the author suggests to curb the conflicts of interest in the field:

  1. Professional organizations should end financial relationships with pharma companies.

  2. Patient organizations should stop their ties with pharma.

  3. Cancer doctors are paid a percentage of the pricy cancer drugs — this needs to stop.

  4. The people who write the guidelines should be without conflict of interest.

  5. We need rules for when & where former FDA employees can work for Pharma.

  6. The party that assesses clinical trials shouldn’t be the one that would earn billions if it’s positive.

At first sight, all of this seems depressing, but it’s not. If we implement the smart measures suggested in the book, drug development incentives will change and become developing useful and cheap drugs for patients, and that’s what we want.

Lastly, Prasad mentions the question of overscreening, explaining that screening a lot doesn’t necessarily lead to better outcomes (I’m thinking a lot about overscreening lately—as Marty Makary also mentions it a lot in The Price We Pay—and will write about it in next week’s edition.) It made me think of the Cobra Effect 👇

🇮🇳 A New Idea of India

I’m fascinated by India, and I try to learn more about Indian culture, civilization, and politics. The book A New Idea of India by Harsh Madhusudan and Rajeev Mantri is an excellent read for everyone interested in the country.

Here’s a quote that stuck with me:

This book makes the case that a ‘civilational republic’—a democratic polity based on the rule of law that in turn is rooted in India’s millenia-old pluralistic ethos—is the surest guarantee of securing the freedom that Palkhivala held so dear. India is the only major civilisational republic in the world today. While China is often described as a civilisation state, and correctly so, it is not a democratic republic.

I’m talking to the two authors of the book next week on The Long Game Podcast; let me know if you have some questions for them!


🎙 Podcast Episode of the Week

🏥 #10: Brennen Hodge on the US Healthcare System and How to Fix it

My guest today is Brennen Hodge. Brennen is the co-founder and CEO of Citizen Health, a health cooperative leveraging direct care and blockchain to build a better healthcare system. He's an expert on everything related to healthcare.

In this conversation, we talk about the US healthcare system's problems, but we try to focus on the solutions. Brennen explains how Citizen Health is targeting the problem through a better ownership model. Brennen also gives the best books to understand the US healthcare system from an outsider's perspective. We finish the conversation talking about his latest project to date, XBuilt, an engineering company developing zero energy-smart homes.


🍭 Brain Food

🍄 What if a Pill Can Change Your Beliefs?

The development of psychedelic therapies isn’t stopping anytime soon. A few weeks ago, Oregon became the first US state to legalize psychedelic mushrooms.

The relationship between psychedelics and religion is fascinating, just as depicted in The Immortality Key by Brian C. Muraresku. The book explores in detail unspoken questions like: Did the Ancient Greeks use drugs to find God? And did the earliest Christians inherit the same, secret tradition?

This article explains that psilocybin treatments can change your religious and political beliefs.

Studies report increased prosociality and aesthetic appreciation, plus robust shifts in personality, values and attitudes to life, even leading some atheists to find God. What’s more, these experiences appear to be a feature, rather than a bug, of psilocybin-assisted psychotherapy, with the intensity of the mystical experience correlating with the extent of clinical benefit.

But to generate a breadth of appeal, one challenge stands out: psilocybin seems to make people more liberal.

On the same note, I loved this podcast episode with Mark Plotkin on Ethnobotany and hallucinogens from the Amazonia.


🎥 What I’m Watching

🛰 Mars in Color

This is an incredible video of the surface of Mars. I can’t stop thinking about whether we will get to see it with our own eyes one day. I hope so.


🔧 The tool of the Week

🧘‍♂️ Otto — Be Mindful while working

Otto is a beautiful and simple Pomodoro timer that also helps you block the distracting websites to focus on the tasks you have to do.


🪐 Quote I'm Pondering

Play long enough and you might get lucky. In the technology game, tomorrow looks nothing like today. If you survive long enough to see tomorrow, it may bring you the answer that seems so impossible today.

— Ben Horowitz


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👋 EndNote

Thanks for reading!

I will see you next week. As always, if you're finding this newsletter interesting, give me your feedback; you can respond to this email or tweet at me!

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Have a great day,

Mehdi

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