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Artificial Intelligence Renders the FDA’s Current Drug Approval Process to be Obsolete

By STEVEN ZECOLA

Artificial intelligence (“AI”) has taken root in the field of drug discovery and development and already has shown signs of running past the traditional model of doing research.  Congress should take note of these rapid changes and: 1) direct the Department of Health and Human Services (“HHS”) to phase down the government’s basic research grant program for non-Ai applicants, 2) require HHS to redirect these monies to fund nascent artificial intelligence applications, and 3) require HHS to revamp the roadmap for drug approvals of AI-driven trials to reflect the new capabilities for drug discovery and development.

Background

There are four distinguishing features of the U.S. healthcare industry.

First, the industry’s costs as a percentage of GNP have increased from 8% in 1980 to 17% today, and are expected to exceed 20% by 2030.  The federal government subsidizes roughly one-third of these costs.  These subsidies are not sustainable as healthcare costs continue to skyrocket, especially in the face of an overall $37 trillion federal deficit.

Second, the industry is regulated under a system that results in an average of 18 years of basic research and 12 years of clinical research for each drug approval.  The clinical cost per newly approved drug now exceeds $2 billion.  The economics of drug discovery are so unattractive to investors that the federal government and charitable foundations fund virtually all basic research.  The federal government does so to the tune of $44 billion per year.  When this cost is spread among the 50 or so drug approvals per year, it adds a cost of roughly $880 million to each drug, bringing the total cost to over $3 billion per drug approval. Worse yet, the process is getting slower and more costly each year.  As such, drug discoveries under the current research approach will not be a significant contributor to lowering the overall healthcare costs.

Third, the Trump administration has undercut the federal government’s role in healthcare by firing several thousand employees from HHS.  Thus, the agency can no longer effectively administer its previously adopted rules and regulations, and therefore, cannot be expected to shepherd drug discovery into lowering healthcare costs.

Fourth, on the positive side, artificial intelligence software combined with the massive and growing computational capacity of supercomputers have shown the potential to dramatically lower the cost of drug discovery and to radically shorten the timeline to identify effective treatments.

Enter Artificial Intelligence (AI) into Drug Discovery

For the past decade, a handful of companies have been exploring advanced automation techniques to improve the many facets of the drug discovery process. Improvements can now be had in fulfilling regulatory documentation requirements, which today add up to as much as 30% of the cost of compliance.  More significantly, Ai can be used to accurately create comprehensive clinical documents from raw data with citations and cross-references – and continually update and validate the documentation.

The top Ai drug discovery companies include Insilico Medicine, Atomwise, and Recursion, which leverage Ai to accelerate various stages of drug development, from target identification to clinical trials. Other notable companies are BenevolentAI, Insitro, Owkin, and Schrödinger, alongside technology providers like Nvidia that supply critical Ai infrastructure for the life sciences sector.

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The ‘After Phase’ Is Missing: Why Every GLP-1 Prescription Needs an Exit

By HOLLI BRADISH-LANE

I’ve seen clients start GLP-1 medications full of hope—and stop them feeling betrayed by their own biology.

Some reached their limit with side effects: relentless nausea, fatigue, or the quiet loss of joy in eating. Others simply couldn’t afford to stay on. A few never saw the promised results at all. But for nearly all of them, the story ended the same way—one step forward, five steps back.

We celebrate the success stories of GLP-1s, but we rarely talk about the crash that follows when treatment stops. And it’s not just psychological. The body rebounds fast—hunger, weight, and metabolic chaos rush back in.

The problem isn’t the medication itself. It’s that we’ve built an elegant on-ramp for GLP-1s—and almost no off-ramp at all.

The Evidence Is Already Warning Us

The data couldn’t be clearer. In the STEP-1 extension trial, participants who stopped semaglutide regained roughly two-thirds of the weight they had lost within one year. Their blood pressure, cholesterol, and blood-sugar levels slid back toward baseline.

A nearly identical pattern appeared in the SURMOUNT-4 trial for tirzepatide: those who continued therapy maintained—or even deepened—their weight loss; those who stopped rapidly regained.

Meanwhile, the SELECT cardiovascular outcomes trial showed semaglutide reduced major cardiac events in people with overweight and obesity. That’s a major win—but also a reminder that stopping abruptly can erase much of the benefit.

Both the American Diabetes Association 2025 Standards of Care and the American Gastroenterological Association guidelines now emphasize continuing anti-obesity pharmacotherapy beyond initial weight loss goals.

The implication is simple: for most patients, GLP-1s are not a 12-week intervention—they’re chronic therapy.

Yet in real life, chronic use isn’t always realistic.

Why So Many Will Stop Anyway

Insurance coverage ends. Supplies run short. A job changes, or a deductible resets. Some patients plan a pregnancy, experience intolerable side effects, or simply want to know who they are without the injection. Others plateau despite perfect adherence and feel the drug has stopped working.

In each case, the result is the same… withdrawal without a plan.

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Justin Schrager demos Vital.io

Justin Schrager is the CMO of Vital.io. Their technology sits in the hospital telling patients what is going on with their care while they are in the hospital, particularly in the ER. Justin showed a deep demo about the patient experience of using Vital.io which includes what the patient can expect and guides them through the confusing workflow. It allows the patient to make requests, and also lots of guidance about what is happening to them, or for example what lab results might mean. It goes as far as helping people book appointments for follow up with the right doctor. We had a great chat about the product and also about the realities of running a tech company that has to integrate with Epic and many other EMRs.–Matthew Holt

A Comprehensive Examination of Primary Care Disparities in California: Navigating the Abyss

By SUHANA MISHRA

Residing in the often overlooked San Joaquin Valley, I’ve personally felt the impact of the shortage of primary care physicians. My family struggled to access basic medical attention for common illnesses like the flu. Getting local doctor appointments wasn’t just difficult—it often meant resorting to urgent care or driving long distances for simple treatments. Non-emergency issues that could have been resolved with accessible primary care instead overwhelmed urgent care centers, which often had long wait times and suboptimal conditions. These firsthand experiences revealed just how critical primary care access is for our community. They also sparked my passion for change. Leading a HOSA community service campaign on California’s physician shortage gave me a clearer view of the systemic nature of the issue—and fueled my determination to seek long-term solutions.

California, despite being a hub of innovation, faces a severe and growing deficit in primary care access. Nowhere is this more apparent than in regions like the San Joaquin Valley. Long travel distances, physician burnout, and systemic neglect manifest in community-wide health decline. A UCSF study reported that only two regions in California meet the federally recommended threshold of 60–80 primary care physicians per 100,000 residents. The San Joaquin Valley, predictably, falls far below this benchmark.

While programs like the Steven M. Thompson Physician Corps Loan Repayment Program attempt to incentivize doctors to practice in underserved areas, the impact is limited. According to CapRadio, a third of California’s doctors are over 55 and nearing retirement. CalMatters estimates that by 2030, the state will be short more than 10,000 primary care physicians. The implications are dire—not only for logistics and care delivery, but also for the long-term health outcomes of Californians.

When patients face barriers to consistent care, chronic conditions go unmanaged.

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Halo, Heresy, and Health Care

By KIM BELLARD

If you are of a certain age – say, mine, that is to say, a Baby Boomer – last week’s announcement that Microsoft was going to release a new version of Halo on Sony’s PlayStation console may have passed you by. So what, you might have said? If, on the other hand, you are one of the three-fourths of Americans who play video games, you might have more immediately grasped the significance.

The gaming industry is like porn industry in that it tends to be early on the technology front. Since I don’t follow the porn industry, I try to watch the gaming industry to see what trends in it may suggest for the future of other industries, especially healthcare.

In case you weren’t aware, Halo is a Microsoft game, and has historically been played on Microsoft’s Xbox console. Sony’s PlayStation is Microsoft biggest competitor, and has been winning the war handily. So making Halo available on PlayStation is a somewhat surprising move. As Zachary Small wrote in The New York Times: “It is the equivalent of Disney letting Mickey Mouse roam Universal Studios.”

Or, as Grant St. Clair marveled in Boing Boing:

I cannot possibly emphasize how big a deal this is, but odds are you already know yourself. Halo is bar none the biggest IP Xbox has, and historically one of the biggest draws to the console. It’d be like Nintendo suddenly putting Super Mario Galaxy on Steam. This is a tacit admission that Xbox has lost the hardware war — the writing was on the wall already, granted, but this italicizes and underlines it.

A gamer told BBC Newsbeat that the announcement was “massive” and “broke the internet a little bit.” She’s happy about the news, adding: “I know there’s a bit of controversy about it coming to PlayStation, but I don’t see any reason why it should be like that at all. I just think it’s a win for all gamers.”

So, whether you realize it or not, this is kind of a big deal.

Microsoft has desperately been trying to stay relevant in gaming. A couple years ago Microsoft shelled out $70 billion to acquire Activision Blizzard, and a couple years prior to that paid $7.5b for ZeniMax Media. Still, though, as Joost van Dreunen, a market analyst and professor at New York University, told Mr. Small: “When it comes to consoles, Xbox has always been the bridesmaid and never the bride. They just haven’t been able to outmaneuver PlayStation and Nintendo.”

It may have found a way. Earlier this year Microsoft made Gears of War and Forza Horizon 5  available on PlayStation, and Microsoft Flight Simulator will join them later this year. Indeed, Mr. Small points out: “Between April and July, six of the top 10 best-selling games on Sony’s consoles were Microsoft properties.”

I.e., if you can’t beat them, join them.

“We are all seeking to meet people where they are,” Matt Booty, the president of Xbox game content and studios, told Mr. Small. Even more interesting, he further explained: “Our biggest competition isn’t another console. We are competing more and more with everything from TikTok to movies.”

Lesson #1: your competitors are not necessarily the ones you think they are.

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The Nobel Prize’s Amazing Track Record in Immunology

By MIKE MAGEE

With the announcement of the 2025 Nobel Prize in Physiology or Medicine last week, the American Association of Immunologists (AAI) took an understandable victory lap, stating: “This Nobel Prize demonstrates how immunology is central to medicine and human health. The ability to harness, modulate, or restrain immune responses holds promise across a vast range of diseases — from autoimmune conditions to cancer, allergies, infectious disease, and beyond.”

This year’s award went to Mary E. Brunkow, Fred Ramsdell and Dr. Shimon Sakaguchi, and it couldn’t have come at a better time as our nation’s scientific community and their governmental, academic and corporate science leaders push back against vaccine skeptic RFK Jr.

As the AAI proudly exclaims, “Since 1901, Nobel Prizes have been awarded to 27 AAI members for their innovation and achievements in immunology and related disciplines.” Make that 28 with the addition of Dr. Sakaguchi, a Distinguished Fellow of AAI.

The field of Immunology and the Nobel Prize in Physiology or Medicine have grown side by side over the past century.

Immunity has Latin roots from the word immunitas which in Roman times was offered to denote exemption from the burden of taxation to worthy citizens by their Emperor.  Protection from disease is a bit more complicated than that and offers our White Blood Cells (WBCs) a starring role. These cells are produced in the bone marrow, then bivouacked to the fetal thymus for instruction on how to attack only invaders, but spare our own healthy cells.

WBC’s are organized in specialized divisions. WBC neutrophils engulf bacterial, fungi, and fungi as immediate first responders. Monocyte macrophages are an additional first line of defense, literally gobbling and digesting bacteria and damaged cells through a process called “phagocytosis.” B-cells produce specific proteins called antibodies, designed to learn and remember specific invaders chemical make-up or “antigen.” They can ID offenders quickly and neutralize target bacteria, toxins, and viruses. And T-cells are specially designed to go after viruses hidden within the human cells themselves.

The first ever Nobel Prize in Physiology or Medicine went to German scientist, Emil von Behring, eleven years after he demonstrated “passive immunity.” He was able to isolate poisons or toxins derived from tetanus and diphtheria microorganisms, inject them into lab animals, and subsequently prove that the animals were now “protected” from tetanus and diphtheria infection. These antitoxins, liberally employed in New York City, where diphtheria was the major killer of infants, quickly ended that sad epidemic.

The body’s inner defense system began to reveal its mysteries in the early 1900s. Brussel scientist Jules Bordet, while studying the bacteria Anthrax, was able to not only identified protein antibodies in response to anthrax infection, but also a series of companion proteins.  This cascade of proteins linked to the antibodies enhanced their bacterial killing power. In 1919 Bordet received his Nobel Prize for the discovery of a series of “complement” proteins, which when activated help antibodies “drill holes” through bacterial cell walls and destroy them.

Victories against certain pathogens were hard fought. In the case of poliovirus, which had a predilection to invade motor neurons, especially in children, and cause paralysis, it required a remarkable collaboration between government, academic medical researchers and local community based doctors and nurses to ultimately succeed. The effort involved simultaneous testing in children of two very different vaccines.

Current vaccine skeptics like RFK Jr. argue against historic facts.

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Let a Thousand DNA Flowers Bloom

By KIM BELLARD

When I saw a headline about “DNA flowers,” I was nonplused. I mean: aren’t all flowers made out of DNA, like every living thing on our planet? Well, it turns out that the DNA flowers are actually soft robots – make that nanobots – so my interest was definitely piqued.

The DNA flowers are out of the Freeman Lab at the University of North Carolina, led by Dr. Ronit Freeman, and the research about them was just published in Nature Nanotechnology with the less sexy title “Reversible metamorphosis of hierarchical DNA-organic crystal.”  Had I seen that before “DNA flowers” I probably would have passed it over, so I’m glad someone has an eye towards marketing.

Designer Daniel Burham famously said: “Make no little plans,” and I kind of think he’d like Dr. Freeman. Her bio says she has formal training in computer science, chemistry, nanotechnology, and regenerative medicine (plus even ballroom dancing, if you’re counting), and she probably needs all that training, because her primary interest is “in supramolecular self-assembly, a field where common biological materials like DNA and proteins are seen not simply as information carriers, but also as tunable structural materials for next-generation sensors, nano robots, drug breakthroughs, and clinical tools.”

Accordingly, what the Lab has done now is to combine DNA with inorganic materials to allow them to respond to their environment. Professor Freeman says: “We take inspiration from nature’s designs, like blooming flowers or growing tissue, and translate them into technology that could one day think, move, and adapt on its own,”

Indeed, the Freman Lab prides itself on “bioinspired technologies,” the purpose of which is: “We engineer living and synthetic materials to accelerate healthier outcomes for global communities.” The website talks about “building block designs.” featuring hierarchical self-assembly, temporal structural reconfiguration, and adaptive behavior.

Hence, DNA flowers. 

The flowers are actually shaped like flowers, although they are microscopic, and what makes them both interesting and potentially useful is that the various strands of DNA allow them to move, open or close, or trigger chemical reactions, based on environmental cues like temperature, acidity, or chemical signals. The DNA sequences guide nanoparticles to organize into complex structures, which can reverse shape as desired.  

“People would love to have smart capsules that would automatically activate medication when it detects disease and stops when it is healed. In principle, this could be possible with our shapeshifting materials,” said Professor Freeman. “In the future, swallowable or implantable shape-changing flowers could be designed to deliver a targeted dose of drugs, perform a biopsy, or clear a blood clot.”

Yeah, I’d love that, and I bet you would too.

The team acknowledges that the technology is in the early stages, but see a future where, say, a DNA flower is injected into a cancer patient, in whom it travels to a tumor, whose acidity causes the petals to release a medication or even take a tiny tissue sample. When the tumor is gone the DNA flower would deactivate until/unless new environmental triggers reactivate it.  

Thinking beyond healthcare, the team sees their creations helping to clean up environmental contamination, or as a great digital storage device — up to two trillion gigabytes in just a teaspoon. 

The fact that the DNA flowers can sense and respond to their environment makes the team believe these are a major step forward in bridging the gap between living systems and machines. We’re going to see more of that in the rest of the 21st century.

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Greg Whisman, CareMore Health

Greg Whisman is the Chief Medical Officer of CareMore Health, a venerable prepaid medical group caring for seniors. It’s been part of Anthem/Elevance for many years but this year spun off as part of a larger PE backed group called Millennium. We really got into the what and the how of primary care for seniors and, yes, we delved deep into the future of primary care. This is a topic that will never die on THCB and getting a real expert to opine on it was really valuable. This is a great conversation–Matthew Holt

Sami Inkinen, Virta Health

Virta Health is in the diabetes reversal business. It’s a medical group that for a decade has been aggressively coaching people with diabetes and cardiometabolic disease to radically change their eating habits–basically to eat the right things for them, to saity. Some how in a nation obsessed with processed food and carbs they have succeeded for a lot of people. And the business is growing fast, with over $160m in annual run rate. Ten years in since it started I spoke with CEO Sami Inkinen about how and why it works, and what the future for this approach is in a world of GLP1s (and no there’s no GLP sales in that revenue number!)–Matthew Holt

Concierge Care for all: What would it look like?

By MATTHEW HOLT

A few weeks back I wrote an article on what’s wrong with primary care and how we should fix it. The tl:dr version was to give every American a concierge primary care physician paid for by the government. We would give everyone a $2k voucher (on average, dependent on age, medical status, location, etc) and have an average panel of 600 people per PCP.

My argument was that a) this would be cheaper than health care now – due to cutting back on Emergency Department visits and inpatient admissions and that b) it would enable us to pay PCPs the same as specialists (roughly $500K a year). This would mean that many current ED docs, internists, hospitalists etc would convert to being PCPs. I also think that we could and would make better use of the now 400,000 nurse practitioners in the US. We would only need about 600,000 PCPs to make this work. Although it would double spending on primary care, it would reduce health care costs overall. (OK there’s some debate about this but the Milliman study linked above and common sense suggests it would save money).

There are obviously two huge issues with my proposal. First we would have to go through the conversion process. Second, we would have to do something big with the three major players who are sucking at the teat of health care $$ right now—those being big hospital systems and their associated specialists, health insurers, and pharma and device companies.

I don’t think that there will be any problem selling this to most doctors or to the American people.

The doctors know that they are trapped in the current system. This would free them to practice as they want to practice, and to remember why they got into medicine in the first place—to care for their patients holistically.

People know all too well that accessing primary care is both good for them and also very difficult. Wait lists are way too long. In this system primary care would be abundant. And I and many others have only horror stories of how big hospital systems, insurers and big pharma treat them badly. They would much rather have an empowered PCP on their side.

The only concern about primary care for patients is if the PCP is incented to not refer them to needed specialty care. In my system there would be no global capitation or risk to the PCP, and thus no incentive not to refer out. But no reason to refer out unnecessarily. They would do the right thing because it is the right thing. (It has taken Jeff Goldsmith 30 years to convince me of this). So there would be no need for insurance companies to manage primary care at all. No claims, no bills, no utilization management. Instead we should have 600,000 primary care docs paid well and able to manage their practices to do the right thing.

And this would probably involve a ton of variation. There would be PCPs who work in groups. There would be solo. There would be those specializing in specific types of patients (think kids or people with serious diseases or geriatricians). They would all make the same amount of salary but their practice’s revenue and number of patients would be adjusted in a similar way to how we do risk adjustment for Medicare Advantage now, but without the games, and with no profit motive.

This system would create a lot of innovation. PCPs would be responsible for those with chronic conditions. They would have budget from the $2,000 per head (of which they would get roughly $800 as income) to build remote monitoring programs, to use AI, to build teams of assistants and nurses et al.

So can it be done in the US? Yes it already has. I urge you to take the time to read this ingenious ChatGPT summary of the Nuka system in Alaska. (I believe created by Steve Schutzer MD). Nuka went from being a hidebound bureaucratic expensive system–that its patients hated–to being a system with culturally appropriate care that its “consumer-owners” love today. And its costs are lower and outcomes better. There are lots of other examples of similar approaches across the US.  Just ask Dave Chase. They just haven’t scaled because the current incumbents have killed them.  (One great example is this case in Texas where a hospital chain bought and killed a big primary care group led by Scott Conard because it was costing them $100m a year in reduced hospital FFS admissions).

What we need is to set up the incentives, prod doctors and patients hard to get into these arrangements and let American ingenuity and medical professionalism go at it.

The other side of the equation is the need to reign in the costs of specialty and hospital care. How this would happen is up for debate.

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