Tremendous

An angel investor's take on life and business

  • I recently received an intriguing short essay from a friend of mine. It gave me a different perspective on what we consider freedom. I’ve published it in full below. Enjoy!

    It’s when thought and action form a single whole that you’re free to be something

    Freedom

    I know a boxing instructor who used to tell his pupils to evade incoming blows intuitively, to block intuitively, to throw punches intuitively.

    This, I think, was an elegant shorthand for saying: Think carefully about what’s really intuitive, and do that. To this boxing instructor, intuition was not just whatever first comes to mind, but above all whatever makes the most sense.

    No one is born a boxer. There may be those who pick it up with remarkable speed, but they, too, must first be shown what to do, and will only progress, maybe to greatness, with years of teaching and practice. For the rest of us, our first reactions to an incoming punch are often wrong: His fist is moving to my right, so I should duck my head to my left. This is fine—if you mean to use your head to block the punch. Otherwise, do what’s truly intuitive: move your head ahead of the punch, in the same direction. Evade the punch intuitively. Then bob back up and give him a left hook to the jaw.

    Intuition must be learned, paradoxical as it sounds. The elegance of a good boxer is nothing other than mastery of a boxer’s intuition. It is not just a mechanical matter of moving quickly and economically; the boxer learns a way of looking, which is as much a way of tuning out what he doesn’t need to know as it is a way of zeroing in on what he needs to react to, or exploit.

    Probably the hardest thing for the intermediate boxer to learn is to look his opponent hard in the eye. If you can deliver your punches without even glancing at where you want them to land, all the better: This is the poker face of boxing. Where poker is all about detachment and nonchalance, in boxing, you avoid betraying your intentions best by locking your gaze on his. The intuitive way to look at someone, in boxing, is the most aggressive, but also the most intimate. It’s a weird invitation: Let’s box.

    Until the pupil achieves a certain dexterity and a certain ease with these psychological demands of the game, he will not be able to integrate what he already knows into an adequate response to his opponent. Maybe he can punch a bag well. The bag swings in predictable ways, never making a fuss. Maybe his footwork looks good in a mirror. You don’t have time to look at your own technique when your opponent is about to punch your liver in.

    To be able to surprise your opponent, you mustn’t give any indication where you’re going to punch. At the same time, you must be alert to whatever your opponent may be planning, which he’s likeliest to betray with his eyes, a split second before he makes his move. And so, there’s only one thing to look at directly: The eyes of your opponent. This, in turn, means you need to split your perception of visual stimuli: You must get used to seeing the motions of his body out of the corners of your eyes. You can’t try to focus on whatever you have to react to or whatever you’re about to do, as you might in everyday life. That’s everyday intuition; what you need is a boxer’s intuition.

    There is, in other words, no way to box but to box intuitively. In the absence of this intuition, you have no way of assessing dangers or opportunities, and your approach to your opponent becomes nothing but an overwhelming sequence of options, which you need to think about consciously, one at a time. In the time it takes you to do that, you’re already on the canvas.

    I think skilled practices like boxing—I could, instead, have written about playing an instrument—give important lessons about the nature of human freedom generally. Because I never feel as free as when the need to make conscious, considered choices drops away, when I no longer need to maintain any kind of split between thought and action. It’s when thought and action form a single whole that you’re free to be something, fully, and being fully human, acquiring a full and human intuition of what you’re on earth to do, is, for me, the only way to be truly free.

    Contrast this with the freedom so often held as an ideal today: The freedom to choose. The more choices you have, the freer you are—so it’s insinuated. But the kinds of choices whose number can be arbitrarily increased—How many vacuum cleaners are on the market? What’s the best ham at the deli? How many men are on the ballot?—are the kinds of choices whose proliferation will crowd your thinking and add noise to your life. And soon you will find yourself accommodating your life to your acquired need to make these choices, over and over again, to feel in control of things, rather than living in order to become who you truly are.

    I think it’s people who view freedom this way who fear death the most. – Think of what I’ll be missing! – Whereas if you’re sure of who you are, of what you’re on earth to do, you can’t help but do it, intuitively, and the time when it must end will always be far off.

  • Photo: Dr. Maciej Boni, Associate Professor of Biology, Pennsylvania State University, study co-author

    Assuming high vaccination coverage (> 28%) and no major relaxations in distancing, masking, gathering size, or hygiene guidelines between now and spring 2021, our model predicts that a combination of vaccination and population immunity will lead to low or near-zero transmission levels by the second quarter of 2021.

    I came across a new study posted on January 15 that analyzes data from Rhode Island and Massachusetts to find optimal vaccine policies and predict when the COVID pandemic will end. With reasonably optimistic assumptions, the authors conclude we may be out of the woods by the second quarter of this year.

    I find their 28% vaccination target plausible. It’s ambitious, but we need to be ambitious right now. Getting to 28% coverage would take about 1.1 million shots a day, 7 days a week, which seems achievable at current rates. ((330 million Americans * 2 shots each * 0.28)/163 days until July 1 = 1,133,742 shots/day).

    We’ve recently passed 1.2 million shots in a day:

    The study also finds that it’s best to vaccinate health workers first and then the elderly, which is what we’re doing.

    In a time when the news is often grim, I find this study very hopeful!

  • Photo: Shengfang Jin, PhD, Vice President and Head of Discovery Biology, Editas Medicine

    This morning, I attended an online presentation by two experts on gene editing and CRISPR. Shengfang Jin, VP of Editas Medicine, and Andrew Lin, who heads the Rare Disease Center at WuXi AppTec, presented a lot of great info, but what stuck out to me most was the trial Editas is doing to cure a rare eye disorder.

    Leber congenital amaurosis type 10 generally causes people to be born blind or lose their sight by age 10. I can only imagine how difficult it must be. A new therapy from Editas targets this disease with a one-and-done treatment. This therapy is the first use of CRISPR in a human being, as opposed to a cell culture, and is currently in Phase 1/2 clinical trials.

    Listening to Dr. Jin speak, I was put in mind of this passage from the Bible:

    “the blind can see, the lame can walk, those who suffer from dreaded skin diseases are made clean, the deaf hear, the dead are brought back to life, and the Good News is preached to the poor. “

    Matthew 11:5

    I increasingly suspect we are at the dawn of a golden age in medicine. The rapid pace of COVID vaccine development or this first in vivo use of CRISPR may be the first signs of things to come.

    P.S. The presentation should be up on the website of Genetic Engineering & Biotechnology News here soon.

  • This weekend, my wife introduced me to an adorable little video series ]that’s become all the rage lately in her home country of Japan. The stop-motion animations feature little guinea pig cars that have adventures, and the sounds are recorded from actual guinea pigs! We’ve enjoyed relaxing in the evenings with these cute videos. Each takes countless hours to make and a new one is uploaded to this YouTube channel every week.

    Pui pui is a onomatopoeia for the sound guinea pigs make. You needn’t speak Japanese or be familiar with Japan to enjoy the series, but those who do/are will notice a few funny tidbits. The restaurant in this video is based on Jonathan’s, a popular (and excellent) family restaurant chain in Japan. But the video renders it Molsan’s, based on “morumotto”, the Japanese word for guinea pig, and “san,” which is like Mr.

    Have fun! 🙂

  • I notice a significant increase in the popularity of conspiracy theories recently. Some are byzantine, with such outrageous claims it’s a wonder they ever gained currency. And they seem to be gaining new adherents by the day.

    Conspiracy theories are nothing new. But why do they seem particularly salient today? Being a part of a group of believers, either in a religion or a conspiracy, provides connection to others and affirmation from a community. In a time of isolation, those are particularly valuable.

    But I think the biggest reason for the popularity of conspiracy theories today is that there is something happening to our world that we don’t understand and can’t control. An invisible illness is spreading globally and mutating steathily. Its origin is unknown. The date it all ends is unknown. Any control we have over it is partial at best. And it’s affecting nearly every person on earth in one way or another.

    As ghoulish as it is, believing that some group of evil humans unleashed this on us intentionally is more comforting than believing that COVID arose purely randomly. At least we could find those evildoers and punish them, and then maybe it stops! Believing the sickness isn’t serious provides an even greater comfort…the terrible things that seem to be happening around us aren’t real! Everything is fine!

    It is hard to accept someone is doing something awful to us on purpose, but at least it would preserve the illusion of human control. That we have no control and are being buffeted by random chance and a natural world that is indifferent to us is even scarier.

    Someone is shaking our ant farm!

    Or so we think. But in reality we are subject to an earthquake, this time of the biological variety. We don’t fully understand what’s happening, but we know something is.

    Conspiracies also gained currency after 9/11. I suspect this is because people found it more comforting to imagine our government was in control, even in a malevolent way, than to believe that a small group of unknowns from the other side of the world could strike at the heart of our nation at any time.

    What’s the solution? I’m not sure there is one, other than time. Distance from the events will give us perspective. But in the mean time, let’s remember that we are affected by randomness every day. Not everything has a pattern, a discernible cause, or a smoke filled room filled with evil, cigar chomping men behind it. Sometimes things just happen, and we have to respond the best we know how.

  • Today I attended a fascinating discussion of the movie Human Nature, a documentary on CRISPR gene editing. Nobel Prize winner Jennifer Doudna, the co-inventor of CRISPR, gave us her perspective on the technology. Author Walter Isaacson and the filmmaker, Adam Bolt, also gave valuable insights.

    Isaacson framed the moment well, saying that CRISPR is part of the 3rd great scientific revolution. The first was in the first half of the 20th century, in physics. The 2nd, in information technology, consumed the second half of the century. And in the 21st century, the revolution is and will be in the life sciences.

    Because CRISPR can make DNA and RNA programmable like computer code, there’s a strong parallel between CRISPR and the IT revolution. What if biology and medicine progressed the way software has in the last few decades?

    Doudna is particularly excited about the applications of CRISPR to cure cancer. CRISPR can be used to program the patient’s immune cells to attack tumors. This echoes what the co-founders of BioNTech said earlier this week at a call I attended.

    Bolt and Doudna also noted that CRISPR was a scientific backwater at first. This really emphasizes the importance of funding basic science with no clear application. We never know where it will lead!

    The first patient to be treated for sickle cell anemia using CRISPR is doing quite well a year later. Doudna and others are hard at work on further applications of this technology. As an investor and as a human being, I am eagerly anticipating these breakthroughs.

    “Jennifer Doudna” by Koninklijke Nederlandse Akademie van Wetenschappen is licensed under CC BY 2.0

  • I just finished watching the superb documentary Human Nature, which details the origins and applications of CRISPR gene editing. The filmmakers interview all the leading people in the field and produce a fascinating and highly accessible narrative.

    I found particularly striking how one of the co-inventors of CRISPR, Jennifer Doudna, enjoyed being in an unknown field at first but also wondered whether the field was neglected because it was a dead end. It shows us what we can accomplish when we overcome our self-doubt!

    You can see the movie and attend a talk tomorrow at 1pm EST with Nobel Laureate Jennifer Doudna here, both free of charge. It’s not often a person gets the chance to ask questions of a Nobel prize winner. I’ll be there!

    P.S. If you’re interested in CRISPR, I recommend this book.)

    “Micah’s DNA” by micahb37 is licensed under CC BY-SA 2.0

  • Today, I came across two new articles that provide a great perspective on the COVID crisis.

    Enjoy!

    “State Public Health Laboratory in Exton Tests for COVID-19” by governortomwolf is licensed under CC BY 2.0

  • I recently received a wonderful letter from a young man named Corey, who is at Rawhide boys ranch. Rawhide is a place that takes in boys who have gotten in trouble with the law and helps them change their lives. Corey was behind in school before he arrived at Rawhide, but he’s done a complete 180 and will graduate high school early at 16!

    This is a rare outcome even for children from the best of circumstances. For Corey to be able to pull that off despite the disadvantages I imagine he’s faced in life is nothing short of astounding.

    I can relate to Corey because Corey was me. 22 years ago, I was in Rawhide too. I had gotten in a lot of trouble as a kid but Rawhide completely changed my life.

    What Rawhide does is take kids from situations where they’re not doing well, puts them somewhere different, and gives them a chance to change. Instead of being around friends that are also going down the wrong path, you’re around more positive people. Instead of having to fight to avoid victimization in difficult circumstances, Rawhide provides a tranquil place to live.

    Corey grew up in Milwaukee, where many people, especially black folks, face few opportunities and a violent environment. I imagine if he had grown up somewhere like where I live now, he probably would’ve never gotten in trouble in the first place. But Rawhide gave him that better environment.

    The letter included an envelope so I could reply to Corey, and I plan to write him later today. It’s wonderful to see a young person doing so well.

    If you want to support Corey and others like him at Rawhide, you can donate here. Your investment will pay the best sort of dividends.

  • Today, I had the opportunity to join a call organized by STAT News with the co-founders of BioNTech, the company behind the highly successful COVID vaccine. Ugur Sahin and Ozlem Tureci are incredibly impressive people. Here were some of the highlights:

    • BioNTech was working on cancer vaccines as COVID appeared, but after Ugur read early reports of COVID cases in China, they realized their technology was well suited to making a COVID vaccine
    • Wuhan is one of the most heavily connected cities in China, perhaps explaining how the pandemic spread so quickly
    • We can’t expect the vaccine rollout to go smoothly right at the beginning, but they are confident we’ll improve as we gain experience
    • We are likely to get some data on asymptomatic infections amongst the vaccinated in February. (This may have implications for how long we have to wear masks, etc.)
    • If we delay the 2nd dose of a COVID vaccine in order to get more people their first dose, we should avoid delaying by too much. Whether we delay is a risk/benefit calculation best left to governments.
    • The new technology they’re most excited about is using immune mechanisms against cancer. They have a drug that’s within weeks of beginning testing.

    These STAT Events are free and open to anyone. It was a fascinating call and I was honored to be able to ask a question to these incredible scientists (the answer is the last bullet point above). The recording of the meeting should go up on STAT’s website soon.