Category: Medicine
Genetic Counseling is Under Hyped
In an excellent interview (YouTube; Apple Podcasts, Spotify) Dwarkesh asked legendary bio-researcher George Church for the most under-hyped bio-technologies. His answer was both surprising and compelling:
What I would say is genetic counseling is underhyped.
What Church means is that gene editing is sexy but for rare diseases carrier screening is cheaper and more effective. In other words, collect data on the genes of two people and let them know if their progeny would have a high chance of having a genetic disease. Depending on when the information is made known, the prospective parents can either date someone else or take extra precautions. Genetic testing now costs on the order of a hundred dollars or less so the technology is cheap. Moreover, it’s proven.
Since the early 1980s the Jewish program Dor Yeshorim and similar efforts have screened prospective partners for Tay-Sachs and other mutations. Before screening, Tay-Sachs struck roughly 1 in 3,600 Jewish births; today births with Tay-Sachs have fallen by about 90 percent in countries that adopted screening programs. As more tests are developed they can be easily integrated into the process. In addition to Tay-Sachs, Dor Yeshorim, for example, currently tests for cystic fibrosis, Bloom syndrome, and spinal muscular atrophy among other diseases. A program in Israel reduced spinal muscular atrophy by 57%. A study for the United States found that a 176 panel test was cost-effective compared to a minimal 5 panel test as did a similar study on a 569 panel test for Australia.
A national program could offer testing for everyone at birth. The results would then be part of one’s medical record and could be optionally uploaded to dating websites. In a world where Match.com filters on hobbies and eye color, why not add genetic compatibility?
Do it for the kids.
Addendum: See also my paper on genetic insurance (blog post here).
New York facts of the day
It’s truly astonishing how fiscally irresponsible New York is. The state budget proposal calls for $254 billion in spending, which is 8.3 percent higher than last year. That comes despite New York’s population having peaked in 2020. It’s a spending increase far in excess of the rate of inflation to provide government services for fewer people.
Ditch compares the New York state budget to the Florida state budget, a sensible comparison since both are big states with major urban and rural areas and high levels of demographic and economic diversity. He finds:
- New York’s spending per capita was 30 percent higher than Florida’s in 2000. It was 133 percent higher last year.
- New York’s Medicaid spending per capita was 112 percent higher than Florida’s in 2000. It was 208 percent higher last year. Florida has not expanded Medicaid under Obamacare, while New York has expanded it more aggressively than any other state. “For perspective, in 2024 New York spent nearly as much per capita on Medicaid ($4,551) as Florida did for its entire state budget ($5,076).”
- New York’s education spending per student is highest in the country, at about $35,000. Florida spends about $13,000 per student. Florida fourth-graders rank third in the country in reading and fourth in math. New York fourth-graders rank 36th and 46th.
- Florida has surpassed New York in population and continues to boom.
Here is more from Dominic Pino.
The Eradication of Smallpox
Excellent, beautifully produced video on the eradication of smallpox. Interesting asides on the connection between the scientific and humanitarian revolutions.
Two Laws
In Italy, you need a doctor’s permission before joining a gym or running a marathon.
In Virginia and many other states, you need an annual auto safety inspection to legally drive.
Which of these laws is the most beneficial/costly? Show your work.
The Deadly Cost of Ideological Medicine
Excellent Megan McArdle column in the Washington Post tracing how we have swung from one form of insanity on vaccine policy to another with barely a pause in between:
In more than 20 years of covering policy, I have witnessed some crazy stuff. But one episode towers above the rest in sheer lunacy: the November 2020 meeting of the CDC’s Advisory Committee on Immunization Practices. Sounds boring? Usually, maybe.
But that meeting was when the committee’s eminent experts, having considered a range of vaccine rollout strategies, selected the plan that was projected to kill the most people and had the least public support.
In a survey conducted in August 2020, most Americans said that as soon as health-care workers were inoculated with the coronavirus vaccine, we should have started vaccinating the highest-risk groups in order of their vulnerability: seniors first, then immunocompromised people, then other essential workers. Instead of adopting this sensible plan, the Centers for Disease Control and Prevention advisory committee decided to inoculate essential workers ahead of seniors, even though its own modeling suggested this would increase deaths by up to 7 percent.
…Why did they do this? Social justice. The word “equity” came up over and over in the discussion — essential workers, you see, were more likely than seniors to come from “marginalized communities.” Only after a backlash did sanity prevail.
…That 2020 committee meeting was one of many widely publicized mistakes that turned conservatives against public health authorities. It wasn’t the worst such mistake — that honor belongs to the time public health experts issued a special lockdown exemption for George Floyd protesters. And of course, President Donald Trump deserves a “worst supporting actor” award for turning on his own public health experts. But if you were a conservative convinced that “public health” was a conspiracy of elites who cared more about progressive ideology than saving lives — well, there was our crack team of vaccine experts, proudly proclaiming that they cared more about progressive ideology than saving lives.
This is one of the reasons we now have a health and human services secretary who has devoted much of his life to pushing quack anti-vaccine theories.
I recall this episode well. Nate Silver and Matt Yglesias deserve credit for publicizing the insanity and stopping it–although similar policies continued at the state level.
Racial Disparities in Mortality by Sex, Age, and Cause of Death
Racial differences in mortality are large, persistent and likely caused, at least in part, by racism. While the causal pathways linking racism to mortality are conceptually well defined, empirical evidence to support causal claims related to its effect on health is incomplete. In this study, we provide a unique set of facts about racial disparities in mortality that all theories of racism and health need to confront to be convincing. We measure racial disparities in mortality between ages 40 and 80 for both males and females and for several causes of death and, measure how those disparities change with age. Estimates indicate that racial disparities in mortality grow with age but at a decreasing rate. Estimates also indicate that the source of racial disparities in mortality changes with age, sex and cause of death. For men in their fifties, racial disparities in mortality are primarily caused by disparities in deaths due to external causes. For both sexes, it is racial disparities in death from healthcare amenable causes that are the main cause of racial disparities in mortality between ages 55 and 75. Notably, racial disparities in cancer and other causes of death are relatively small even though these causes of death account for over half of all deaths. Adjusting for economic resources and health largely eliminate racial disparities in mortality at all ages and the mediating effect of these factors grows with age. The pattern of results suggests that, to the extent that racism influences health, it is primarily through racism’s effect on investments to treat healthcare amenable diseases that cause racial disparities in mortality.
In other words, much of the discourse on this topic is quite off. That is from a new NBER working paper by Robert Kaestner, Anuj Gangopadhyaya, and Cuiping Schiman.
How America Built the World’s Most Successful Market for Generic Drugs
The United States has some of the lowest prices in the world for most drugs. The U.S. generic drug market is competitive and robust—but its success is not accidental. It is the result of a series of deliberate, well-designed policy interventions.
The 1984 Hatch-Waxman Act allowed generic drug manufacturers to bypass costly safety and efficacy trials for previously approved drugs by demonstrating bioequivalence through Abbreviated New Drug Applications (ANDAs). To spur competition, the Act also granted 180 days of market exclusivity to the first generic filer who challenges a brand-name patent—a mini-monopoly as a reward for initiative. Balancing static efficiency (P=MC) with dynamic efficiency (incentives for innovation) is hard, but Hatch-Waxman mostly got it right.
The Generic Drug User Fee Amendments (GDUFA), modeled after the very successful Prescription Drug User Fee Act (PDUFA), require generic manufacturers to pay user fees to the FDA. These funds allow the Office of Generic Drugs to hire more staff and meet stricter approval timelines. GDUFA dramatically reduced ANDA backlogs and accelerated market entry, especially under GDUFA II.
Generic Substitution Laws allow—or in some states even require—pharmacists to substitute a generic for a more expensive brand-name drug unless the prescriber writes “dispense as written.” This gives generics immediate access to the full market without the need for marketing to doctors or patients. The generic drug market has thus become focused on price as the means of competition. Pharmacists also often earn a bit more on generics due to reimbursement spreads, giving them a financial incentive to substitute. And while pharmacy benefit managers (PBMs) are often criticized, they have also been effective promoters of generics by steering patients toward lower-cost options via formulary design.
The FDA’s Division of Policy Development in the Office of Generic Drug Policy also played an underappreciated but vital role in producing recipes for generics, which has opened up the market to smaller firms. Former FDA commissioner Scott Gottlieb writes:
The division’s core responsibility was drafting, reviewing, and approving the policy guidance documents that defined precisely how generic versions of branded medications could be developed and brought to market. For many generic drugmakers, these documents were indispensable — step-by-step recipes detailing how to replicate complex drugs. Without these clear instructions, numerous generic firms could find themselves locked out of the market entirely…the dramatic increase in the quantity and sophistication of guidance documents issued by the FDA during Trump’s first term was instrumental to his administration’s record-setting approvals of generic drugs and the substantial cost savings enjoyed by patients.
Unfortunately, the Trump administration DOGEd this division—an unforced error that should be reversed. The generic drug market is one of the great policy successes in American healthcare. It works. And it should be strengthened, not undermined.
Noah on health care costs
…in 2024, Americans didn’t spend a greater percent of their income on health care than they did in 2009. And in fact, the increase since 1990 has been pretty modest — if you look only at the service portion of health care (the blue line), it’s gone up by about 1.5% of GDP over 34 years.
OK, so, this is total spending, not the price of health care. Is America spending less because we’re getting less care? No. In cost-adjusted terms, Americans have been getting more and more health care services over the years…
So overall, health care is probably now more affordable for the average American than it was in 2000 — in fact, it’s now about as affordable as it was in the early 1980s. That doesn’t mean that every type of care is more affordable, of course. But the narrative that U.S. health costs just go up and up relentlessly hasn’t reflected reality for a while now.
Here is the full post, which covers education as well.
No Evidence of Effects of Testosterone on Economic Preferences
There is conflicting evidence on whether testosterone affects economic preferences such as risk taking, fairness and altruism, with the evidence suggesting significant effects coming from correlational studies or small underpowered testosterone administration studies. To credibly test this hypothesis, we conducted a large pre-registered double-blind randomized controlled trial with N = 1,000 male participants; 10–20 times larger than most previous randomized controlled studies. Participants were randomly allocated to receive a single dose of either placebo or intranasal testosterone. They thereafter carried out a series of economic tasks capturing social preferences, competitiveness and risk preferences. We fail to find any evidence of a treatment effect for any of our nine primary outcome measures, thereby failing to conceptually replicate several previous studies reporting positive findings that used smaller sample sizes. In line with these results, we furthermore find no evidence of an association between basal testosterone and economic preferences, failing to also conceptually replicate previous correlational studies.
My excellent Conversation with Theodore Schwartz
Here is the audio, video, and transcript. Here is part of the episode summary:
Tyler and Ted discuss how the training for a neurosurgeon could be shortened, the institutional factors preventing AI from helping more in neurosurgery, how to pick a good neurosurgeon, the physical and mental demands of the job, why so few women are currently in the field, whether the brain presents the ultimate bottleneck to radical life extension, why he thinks free will is an illusion, the success of deep brain stimulation as a treatment for neurological conditions, the promise of brain-computer interfaces, what studying epilepsy taught him about human behavior, the biggest bottleneck limiting progress in brain surgery, why he thinks Lee Harvey Oswald acted alone, the Ted Schwartz production function, the new company he’s starting, and much more.
And an excerpt:
COWEN: I know what economists are like, so I’d be very worried, no matter what my algorithm was for selecting someone. Say the people who’ve only been doing operations for three years — should there be a governmental warning label on them the way we put one on cigarettes: “dangerous for your health”? If so, how is it they ever learn?
SCHWARTZ: You raise a great point. I’ve thought about this. I talk about this quite a bit. The general public — when they come to see me, for example, I’m at a training hospital, and I practiced most of my career where I was training residents. They’ll come in to see me, and they’ll say, “I want to make sure that you’re doing my operation. I want to make sure that you’re not letting a resident do the operation.” We’ll have that conversation, and I’ll tell them that I’m doing their operation, but that I oversee residents, and I have assistants in the operating room.
But at the same time that they don’t want the resident touching them, in training, we are obliged to produce neurosurgeons who graduate from the residency capable of doing neurosurgery. They want neurosurgeons to graduate fully competent because on day one, you’re out there taking care of people, but yet they don’t want those trainees touching them when they’re training. That’s obviously an impossible task, to not allow a trainee to do anything, and yet the day they graduate, they’re fully competent to practice on their own.
That’s one of the difficulties involved in training someone to do neurosurgery, where we really don’t have good practice facilities where we can have them practice on cadavers — they’re really not the same. Or have models that they can use — they’re really not the same, or simulations just are not quite as good. At this point, we don’t label physicians as early in their training.
I think if you do a little bit of research when you see your surgeon, there’s a CV there. It’ll say, this is when he graduated, or she graduated from medical school. You can do the calculation on your own and say, “Wow, they just graduated from their training two years ago. Maybe I want someone who has five years under their belt or ten years under their belt.” It’s not that hard to find that information.
COWEN: How do you manage all the standing?
And:
COWEN: Putting yourself aside, do you think you’re a happy group of people overall? How would you assess that?
SCHWARTZ: I think we’re as happy as our last operation went, honestly. Yes, if you go to a neurosurgery meeting, people have smiles on their faces, and they’re going out and shaking hands and telling funny stories and enjoying each other’s company. It is a way that we deal with the enormous pressure that we face.
Not all surgeons are happy-go-lucky. Some are very cold and mechanical in their personalities, and that can be an advantage, to be emotionally isolated from what you’re doing so that you can perform at a high level and not think about the significance of what you’re doing, but just think about the task that you’re doing.
On the whole, yes, we’re happy, but the minute you have a complication or a problem, you become very unhappy, and it weighs on you tremendously. It’s something that we deal with and think about all the time. The complications we have, the patients that we’ve unfortunately hurt and not helped — although they’re few and far between, if you’re a busy neurosurgeon doing complex neurosurgery, that will happen one or two times a year, and you carry those patients with you constantly.
Fun and interesting throughout, definitely recommended. And I will again recommend Schwartz’s book Gray Matters: A Biography of Brain Surgery.
Montana Bucks the FDA, Establishes Biotech and Longevity Hub
Longevity: The US state of Montana this week enacted a groundbreaking law that opens the door for clinics and physicians to provide experimental drugs and therapies that have not received approval from the US FDA. The new legislation, known as Senate Bill 535, was signed this week by Governor Greg Gianforte and builds upon the state’s recent expansion of so-called “Right to Try” laws.
Niklas Anzinger, the head of decentralized longevity initiative Infinita City, has long emphasized regulatory zones as a pathway to broader acceleration of therapies, and referred to the new law as a “groundbreaking moment.”
The original SB 422, passed in October 2023, expanded Right to Try access to all patients – not just the terminally ill,” he told us. “That was the first step in enabling a preventative, longevity-focused model of healthcare, rather than reactive sick care. But a major gap remained: there was no clear regulatory pathway. Uncertainty around liability, payments, insurance, and the blurred lines between drug development and clinical care left the field in limbo. SB 535 changes that.”
The new bill establishes a formal licensing framework for healthcare facilities to become experimental treatment centers. These centers can recommend and administer nearly any experimental drug manufactured within Montana, provided it has passed Phase 1 trials.
The law positions Montana as a potential hub for medical tourism and biotech innovation. The bill has been supported by libertarians and the life extension movement. Key backers saw Honduras’s Prospera (previous MR posts on Prospera) as a model. Note, however, that the law passed the Montana legislature with bipartisan backing, reflecting broad appeal for expanding medical access.
Maybe American Federalism isn’t dead yet.
H5N1 Hasn’t Gone Away
Trump dominates the news cycle but it’s important to remember that events continue even when not watched. In particular, we are not winning against H5N1. Here’s a summary of a recent paper in Science:
High-pathogenicity avian influenza subtype H5N1 is now present throughout the US, and possibly beyond. More cattle infections elevate the risk of the virus evolving the capacity to transmit between humans, potentially with high fatality rates. Nguyen et al. show that from a single transmission event from a wild bird to dairy cattle in December 2023, there has been cattle-to-poultry, cattle-to-peridomestic bird, and cattle-to-other mammal transmission. The movement of asymptomatic dairy cattle has facilitated the rapid dissemination of H5N1 from Texas across the US. Evolution within cattle, assessed using deep-sequencing data, has detected low-frequency sequence variants that had previously been associated with mammalian adaptation and transmission efficiency.
My thoughts on pharma pricing for The Free Press
Here is an excerpt:
Begin with a basic fact. Generics account for about 90 percent of all prescriptions, and for those drugs Americans pay less than the OECD (Organization for Economic Cooperation and Development) average. So while Americans do pay much higher prices for many new drugs, most of the time, for drugs like metformin, atorvastatin, and amoxicillin, they are getting a bargain.
Furthermore, high American healthcare expenditures are in line with our penchant for higher consumption spending in other sectors of the economy as well. Compared to Europeans, we also spend more on leisure and just about everything else.
Here is the full piece — don’t be a Supervillain!
“New Information Suggests Senior Pfizer Executives Conspired to Delay COVID-19 Vaccine Clinical Testing to Influence 2020 Election”
Here is one link. And more. And some CNN coverage. One of the few conspiracy theories I believe in.
And hey people, do you know why this, if it is true, is a real crime? Because the vaccines worked and saved many, many lives.
Talk to some vaccine scientists if you are still confused about this one.
Via Kyle.
Covid sentences to ponder
Tim Vanable: I wonder about the tenability of ascribing a policy like extended school closures to a “laptop class.” Support for school reopenings did not fall neatly along educational lines. The parents most reluctant to send their kids back to school in blue cities in the spring of 2021 were black and Hispanic, research has consistently found, not white. And the most organized opposition to school reopenings, as you know, came from teachers’ unions, who can hardly be considered stormtroopers of the managerial elite.