Progress Deferred: Lessons From mRNA Vaccine Development (Tim Hwang, 2/20/24, IFP)

One institutional reform that may have alleviated this issue would be to use mechanisms that encourage funders to make higher variance, heterodox bets against this kind of scientific consensus. This might include “golden ticket” mechanisms that allow reviewers that feel strongly about a research proposal to fund a project even against the consensus of their peers.52 Similarly, funding programs might be launched to deliberately offer “last shot” funding for potentially high-impact areas that see a period of declining funding and researcher activity.53 These might counter a natural risk-aversion that leads researchers to abandon problems too early in the face of high-profile failures, as they arguably did in the mRNA case. These mechanisms might have particular applicability in cases parallel to mRNA, where expert judgments are based more on analogies to similar problems and where the technology in question would have a major social impact if viable.

The merit of such an approach is bolstered by examining the funders that unusually did choose to fund mRNA research, even during the period in which it faced major skepticism. These organizations did so in part because they were free to prioritize more speculative, high-risk exploration. The specific reasons for this vary. Dan Wattendorf – who led the DARPA ADEPT program that funded mRNA work in the 2010s – attributes the agency’s willingness to support mRNA work to an organizational norm of providing managers like himself free rein to direct their programs.54

The Bill and Melinda Gates Foundation was also an early supporter of mRNA vaccines, providing a $20M grant to Moderna in 201655 and later $55M to BioNTech in 2019.56 These investments were based in part on the personal interest of Gates in advancing vaccine technologies, and since the foundation prioritized finding promising but overlooked methods in related fields. BioNTech had begun working on mRNA therapeutics to address cancer, but was supported by the “[Gates] Foundation [because it] often looked at ‘adjacent’ scientific disciplines whose innovations might help fight infectious diseases…‘We were doing a lot of horizon-scanning to see what the trends were, what was changing, and who were the cutting-edge people,’ Stuart [a director at the Gates Foundation] says, ‘and BioNTech clearly surfaced.’”57

Intervention 2: Address market failures in the “scientific marketplace”

Established pharmaceutical companies were well-positioned to accelerate the development and deployment of mRNA vaccines. These companies possessed the necessary research talent, financial resources, and practical mass production know-how to transform the technology into a workable product.

Despite being well-positioned to lead the way, pharmaceutical companies did not.

The government is a market force.


Treatment can do more harm than good for prostate cancer (Jinping Xu, 1/26/24, The Conversation)

Although about 1 in 8 men in the U.S. will be diagnosed with prostate cancer during their lifetime, only about 1 in 44 will die from it. Most men diagnosed with prostate cancer die from other causes, especially those with a low-risk prostate cancer that usually grows so slowly it isn’t life-threatening.

However, until about a decade ago, most men diagnosed with low-risk prostate cancer were immediately treated with surgery or radiation. […]

Due to widespread PSA screening in the U.S., over half of prostate cancers detected through screening are low-risk. Concerns about overdiagnosis and overtreatment of low-risk cancers are the main reasons why screening is not recommended unless patients still want to be screened after discussing the pros and cons with their doctor.


Most Supplements Don’t Work. But That’s Not the Worst Part. (Alex Hutchinson, Jan 16, 2024, Outside)

But it’s not just the opportunity cost: paradoxically, taking what seems like a shortcut to better performance can nudge you toward doing a worse job on the basics.

A 2011 study in Taiwan illustrates this. Researchers gave a group of volunteers an inert supplement, telling half of them that it was a multivitamin and the other half that it was a placebo. Both segments thought they were helping with consumer product research, providing feedback on the size, shape, and texture of the pill. Then they completed a series of bogus consumer tests while the researchers monitored their behavior. While testing a pedometer, for example, those who thought they’d taken a multivitamin didn’t walk as far as the placebo group; at lunch, they were more likely to overdo it at the buffet table than to select the healthy organic option. In a questionnaire, the vitamin group reported less desire to exercise and greater desire for “hedonic activities” like drinking and—strikingly—casual sex.

As improbable as these results seem, they fit within a larger body of research on a psychological phenomenon called licensing. We often pursue goals that are in conflict with one another, like having an active social life while still getting plenty of sleep. When we make progress toward one goal, we feel justified balancing things out in the opposite direction. Have an afternoon nap and you might think it’s OK to stay out that night for one more drink. When it comes to supplements, the calculus is almost always lopsided. We dramatically overestimate the benefit, and subsequent licensing leaves us worse off than we started.


Why our fear of cancer is outdated — and harmful (David Ropeik, January 8, 2024, Washington Post)

We now know that tens of thousands of common breast, prostate and thyroid cancers that are detected early never go on to do any harm. People “overdiagnosed” with these types of cancer are understandably frightened and usually choose more aggressive treatment than their clinical conditions require. Such “fear-ectomies” cause great harm, leading to side effects that range from moderate to severe and include death itself. We spend an estimated $5.2 billion a year on such clinically unnecessary treatment, 3 percent of the total spent on all cancer care annually.

The Centers for Disease Control and Prevention reported that in 2017, nearly 16 million people were screened for cancer even though they were younger or older than those for whom screening is recommended, based on who is more likely to be helped or harmed (by false positives, the side effects from follow-up diagnostic tests, and aggressive treatment for clinically non-threatening disease discovered in screening). We spend a minimum of $9.2 billion per year on this overscreening.

A majority of people believe that most cancer is caused by environmental carcinogens. Yet we now know that cancer is principally a natural disease of aging, which allows DNA mutations that cause uncontrolled cell growth to accumulate. More than half of those diagnosed with cancer in the United States are at least 65 years old, while 87 percent of those who die of it are 50 or older.

Yet governments spend hundreds of billions of dollars each year to reduce the risk from environmental carcinogens, vastly more than on any other environmental health threat, including fine-particulate air pollution, which kills more than 100,000 people a year. We spend billions on organic foods, vitamins and supplements, as well as many other products that promise to reduce our risk of cancer but don’t. The public has voted against fluoridating the drinking water in public supply systems serving 30 percent of Americans, despite a lack of evidence to support the fear that fluoridation is a cancer risk. Fear of ionizing (nuclear) radiation, a vastly smaller cancer risk than commonly believed, has driven the cost of building nuclear power plants so high that this source of non-greenhouse-gas-emitting energy struggles to compete in the energy marketplace.


Wound healing affected by perception of time that’s passed (Bronwyn Thompson, January 03, 2024, New Atlas)

For the first time, scientists have been able to establish that our perception of the passing of time can independently influence how a wound will heal. While preliminary, this novel study opens the door to a better understanding of the mind-body connection and its role in healing, pain management and more.

Through at-home self-reporting and controlled laboratory sessions, Harvard University researchers found that the skin inflammation left by a suction cup (used in ‘cupping’ therapy) was noticeably diminished for people who perceived more time had passed since the wound was inflicted – even though the time period remained constant across all groups.


Anticipating the Uses of the new AI: robots, mentors, animations (ARNOLD KLING, DEC 25, 2023, In My Tribe)


We bounce our problems off of other people. They might be friends, therapists, coaches, mentors, etc. A lot of what goes on in a coaching or therapy session is that we our nudged into figuring things out for ourselves.

My sense is that the new AI’s are already surprisingly good at playing the role of mentor or coach. People are already using them that way. I imagine that they could get even better. For example, an AI mentor or coach could be trained to imitate a successful role model. Instead of going to see an average therapist or coach, you could have a session with one of the absolute best.

Does a young man benefit from sitting in an audience of hundreds watching Jordan Peterson? What if he could have a one-on-one consult with a Peterson=trained AI?

As an investor, do you see yourself following the advice of Warren Buffet? What if you could have Buffet’s opinion about how you should be selecting a under your circumstances?

My simple essay grader was a convincing proof-of-concept for me. If I were a high school teacher or college professor, I would be happy to use an AI to grade student papers. That would address one of the most tedious, time-consuming parts of teaching.

But more generally, I think that one-on-one relationships between AI’s and humans are going to be important going forward. Everyone can benefit from friendly coaching.

“You’ve got a friend in me.”


Going for a walk wasn’t really a thing 300 years ago – the Victorians turned it into a popular pastime (Lauren Nichola Colley, 12/27/23, The Conversation)

You might be surprised to hear that “going for a walk” wasn’t really a thing until the late 1700s.

The term “pedestrianism” may have Latin roots, but in the 1800s its first association would have been a sporting one. “Professional pedestrianism” or “race-walking” was fiercely competitive by the 1850s.

Tournaments in America took place over six days, with entrants walking the equivalent of 450 miles, taking naps in tents by the track and sipping champagne en route. The stringent “heel-to-toe rule” still in place states that “the advancing leg must be straightened from the moment of first contact with the ground.”

Walking as a leisure activity came about around the 1780s. Until this point walking had been an act of necessity, associated with poverty, vagrancy and even criminal intent. Many individuals would live and die never having seen beyond a few square miles of bleak cityscape and only slightly further for those in the country.

Along with the rural appreciation of the Lake poets – including William Wordsworth and Samuel Taylor Coleridge – at the turn of the century, famous walkers such as Charles Dickens brought the pastime of walking into vogue.


A New Way to Treat Back Pain (Sumathi Reddy, Dec. 21, 2023, WSJ)

What if the best way to treat your chronic back pain is by retraining your brain?

That’s the premise of a novel approach to chronic pain. Many people feel pain even after a physical injury has healed or when doctors can’t find a physical cause. The approach, called “pain reprocessing therapy,” tries to train the brain not to send false pain signals. Some early results are promising.

In a study published last year in JAMA Psychiatry, 66% of a group of people who did the therapy for a month were pain-free or nearly pain-free up to a year later.