17
Mar
2025

Why Cell & Gene Therapy Companies Should Talk with RFK Jr.

Tim Hunt, CEO, Alliance for Regenerative Medicine

As the CEO of the cell and gene therapy advocacy organization the Alliance for Regenerative Medicine (ARM), I’ve been asked one question more than any other amid the constant barrage of news headlines the past two months.

How are you approaching the Trump Administration?

I hear it from across our community, including biotechnology companies, academic and medical research institutions, patient advocacy groups, investors, and our Board of Directors.

Here is how I explain it, starting with important context.  For many of our major stakeholders, cell and gene therapy (CGT) represents highly disruptive technology, much more akin to AI than small molecules. It elicits tremendous hope but also raises justifiable questions and concerns — from patients, payors, policy leaders, and religious leaders. So, we engage with everyone to share our views on the technology and meet people where they are. Everyone gets our respect and our time.

We are treating the new Administration and Congress the exact same way.

I first came to Washington, DC, as a young man during the George H.W. Bush Administration and I’ve seen challenges and opportunities associated with every administration since. At ARM, it’s our duty to recognize — and operate within — this reality and advocate for the patients we serve. 

During the first Trump Administration, the FDA approved the first gene therapies for rare genetic diseases and the first CAR-Ts for blood cancers and proposed a rule that encouraged the use of outcomes-based payment arrangements in Medicaid. But the same administration proposed tying the prices of physician-administered drugs in Medicare Part B to the prices paid in foreign countries, which would have dramatically reduced prices and discouraged further investment in cell and gene therapy startups. The Trump Administration also implemented an immigration ban that harmed the biotechnology workforce.

The Biden Administration took similar positions with regard to our industry. It started the Centers for Medicare and Medicaid Services’ Cell and Gene Therapy Access Model, a welcome effort to modernize Medicaid by facilitating the use of outcomes-based agreements for the FDA-approved gene therapies for sickle cell disease. But skyrocketing inflation — and the rise in interest rates that came with it — depressed investment in development-stage biotechnology companies that create many of the most innovative therapies. And the Inflation Reduction Act, which gave Medicare the ability to drive down prices it pays for a certain number of medicines each year, hit the large biopharmaceutical companies that are often the engines of commercialization for cell and gene therapies through partnerships and acquisitions.

So, with that understanding, when the opportunity arose last week to meet with US Health and Human Services Secretary Robert F. Kennedy, Jr., with a small group of healthcare stakeholders on regenerative medicine, I jumped at the opportunity.

While it wouldn’t be appropriate for me to share specific details about an off-the-record meeting, I can say Secretary Kennedy and his team were highly engaged, asked good questions, and appeared eager to support the field on behalf of the patients we serve. I left the meeting thinking there is important work we can do together to fine-tune the federal regulatory and reimbursement approaches to CGTs to balance safety, efficacy, and speed, and to break down barriers to access.

Beyond that particular meeting, we generally think there is a philosophical alignment between CGTs and aspects of the Make America Healthy Again (MAHA) movement. CGTs address the root cause of disease and can reduce the need for ongoing chronic interventions. Indeed, when the Trump Administration announced the MAHA Commission in February, it cited the work it did during the first term to accelerate advancements in genetic treatments for sickle cell disease.

For CGTs to flourish and reach patients in need, and for the US to outcompete rising powers like China, we need an ecosystem that combines trailblazing science, flexible regulation, modernized healthcare systems, and robust capital markets.

There are three priority areas that we’re discussing with the Administration and Congress:

  • A strong and innovative regulatory framework: The Center for Biologics Evaluation and Research (CBER) has modernized its regulatory approach, harnessed expertise, and hired critical staff in the Office of Therapeutic Products to prepare for the coming wave of CGTs. CBER and OTP have demonstrated an outstanding commitment to reform and improvement in line with scientific advancement. The changes have been particularly notable over the past 18 months – and our community wants to see this progress continue through appropriate resourcing and continuity of the strong CBER/OTP leadership.
  • Patient access to CGTs: Patients who need CGTs should be able to access them, regardless of whether they are on private or public insurance. The Administration has correctly noted that our current healthcare system is designed for chronic medical interventions rather than preventive treatment. We must better align financial incentives with health outcomes and promote the use of value-based payment models in Medicaid in particular. There is a lot that CMS can do under its existing statutory authority to support payment innovation and alleviate structural and administrative barriers to care, including the lack of uniformity in physician credentialing standards that make it difficult for Medicaid patients to travel across state lines to receive specialized care. Secretary Kennedy has expressed an eagerness to leverage existing rules and regulations to make changes that don’t require action from Congress.
  • Investment in biomedical research: Maintaining robust public and private investment in scientific research is a cornerstone of CGT innovation. The NIH has been instrumental in advancing our understanding of genetic diseases and cancers and supports research on ultra-rare conditions for which treatments may lack a viable commercialization pathway. Without ongoing support for scientific discovery, we risk falling behind in the global race for the next generation of treatments.

We strive to find common ground with this, and any other, administration because our patients for the most part do not have other treatment options they can turn to. As the father of a young man with a rare brain condition (Dandy-Walker Syndrome), I am aware of the joys, but also the many juggles and struggles that take place in our community. I’ve met countless CGT patients who have benefitted from our advanced therapies, but also many families who have lost loved ones to cancer and rare genetic diseases.  

When it’s about the future of CGT and our patients, not engaging is never an option.

Tim Hunt is CEO of the Alliance for Regenerative Medicine

17
Mar
2025

CAR-T cell Therapies Made In the Body: Andy Scharenberg on The Long Run

Andy Scharenberg is today’s guest on The Long Run.

Andy is the co-founder and CEO of Seattle-based Umoja Biopharma. The company is developing in vivo CAR-T cell therapies. The idea is to use gene therapy, delivered in a single shot, that can reprogram T cells of the immune system to recognize markers on cancer cells and then hunt down cancer cells and kill them like an invading virus.

Andy Scharenberg, co-founder and CEO, Umoja Biopharma

CAR-T cell therapies have been around for years, and they have delivered remarkable, lifesaving results for patients with certain forms of blood cancer. But these treatments are engineered in a complex, time-consuming, and expensive process. It depends on carefully controlled lab environments where a patient’s precious T cells get engineered, then shipped back to the patient and re-infused. Umoja is hoping to sidestep this so-called “ex-vivo” work – outside the body – and save everyone a lot of time and money by coaxing the body to achieve a similar result “in vivo” or inside the body.

Umoja raised $100 million in a Series C financing at the start of 2025 and is advancing programs through early clinical testing for cancer and autoimmunity. The company and its R&D partners hope to have an early glimpse of clinical trial results before the end of 2025. If successful, this could represent a paradigm shift in the field of cell therapy.

Now before we get started, a word from the sponsor of The Long Run. 

This is a message to drug hunters who are up for a challenge. Are you ready? Here it is: there’s a new prize competition to spur discovery of drugs targeting TBXT. It’s a transcription factor involved in a number of cancers. The competition is offering more than $500,000 in prizes to investigators or companies who identify potent TBXT binders. The great part is that you only need to come up with the compounds; the competition organizers handle biophysical evaluation of submitted compounds. All the resulting data is returned to you confidentially. And you keep all IP rights.

TBXTchallenge.org

My friends at The Linus Group helped craft a survey so you can provide me some feedback on what you like, what you don’t, and what you’d like to see more or less of from this podcast. It only takes 5 minutes, and if you complete the survey, you will be entered with a chance to win one of three complimentary annual subscriptions to Timmerman Report (a $199 value). 

Complete the survey

Now, please join me and Andy Scharenberg on The Long Run.

11
Mar
2025

NIH Cuts Hit Young Scientists the Hardest

David Baker, professor of biochemistry, University of Washington; director, Institute for Protein Design

[Editor’s note: David Baker gave this speech to Seattle community leaders Mar. 10, at a celebration of his 2024 Nobel Prize in Chemistry.]

Let me just briefly tell you how innovation arises in biomedicine and where drug discoveries come from.

A large percentage of the innovation is made at universities by graduate students and postdocs. Often, they take their ideas and spin out biotech companies, and the biotech companies further develop these and the ideas eventually transition to pharmaceutical companies.

It might be surprising to many people that most of the innovation doesn’t happen in the big companies. It happens at universities. The universities also train the workforce for the biotech and the pharmaceutical companies.

So there’s this idea that cutting funding can maybe revitalize a company.

My main message tonight is that exactly the opposite is true for science. That’s because of the critical role that graduate students and postdocs play.

In face of uncertainty about funding, universities are cutting way back on graduate school admissions. For example, in my department, the acceptance rate, the number of students admitted has gone down by more than a factor of two. That’s true across the country.

It’s going to be much harder for students next year who want to pursue careers in science to become scientists. Next, because of the way in which program managers have been fired, there’s a lapse in renewing the flow of funding, so labs are stuck without funding, which makes it very, very hard for the graduates and postdocs in research labs.

Now, because of the uncertainty, universities are imposing hiring freezes. That’s happened in the University of Washington School of Medicine. It is a very reasonable response, because we don’t know where the money is coming from.

That means new postdocs can’t be hired. It’s also means individual labs don’t know if they’re going to have funding. And then finally, for postdocs transitioning to become faculty members, faculty job searches are being canceled across the country. Again because of this uncertainty.

The cumulative effect of this uncertainty is way out of proportion to the amount of funding saved. It doesn’t actually save that much money to have all this uncertainty. It just wreaks havoc on a system which then has to behave conservatively, because it can’t pay people if there isn’t money coming in.

There’s a final aspect to this, which is, many, many outstanding researchers come to the United States from foreign countries. With this uncertainty, the US is getting less attractive as a place to stay. So people are having to return to their home countries. So the US is losing out on all this talent.

I’m telling you this to give you a few more talking points with people that you’re speaking with. I think these things could really have a very long-term effect, a negative effect, not just in biomedicine, but across science overall.

The bottom line is that uncertainty is really bad for science. It hits people at the most delicate time in their career. It hits early on, like when undergraduate students want to become graduate students, or graduate students want to become postdocs or postdocs who want to become faculty members.

That’s the message to spread. Now we’ll move on to more positive things.

David Baker is a professor of biochemistry at the University of Washington and director of the Institute for Protein Design. 

9
Mar
2025

Scientists Standing Up in Seattle

Arjun Kumar

Several thousand scientists gathered Friday in Seattle for one of the nationwide “Stand Up for Science” protests. People studying a range of disciplines — biology, climate change, public health and more — took a break from the lab to protest cuts to federal spending on science and mass firings.

Morale had been low for weeks among many attendees, but Friday had a different mood. Scientists and their allies of all ages gathered on the amphitheater grass under a rare sunny Seattle day.

Speakers stood below the iconic Space Needle and drew thunderous applause. Some wore white lab coats while others waved American flags. Many brought their dogs. Two protestors even dressed in chicken costumes, calling attention to the rising outbreak of bird flu in the U.S.

Despite the lighter aspects, participants had a serious purpose. Carrying signs with messages like “Science Saves Lives”, “No Science, No Cures”, and “Dump DOGE, Defend Our Data”, they had three core policy demands:

  • An end to censorship and political interference in science, including removing restrictions on research topics eligible for federal funding and restoring public access to scientific data scrubbed from federal websites
  • Restoration of federal research funding, including removal of the 15% cap on indirect funding for NIH grants, and reinstatement of wrongfully dismissed federal employees
  • Preservation of diversity, equity, inclusion, and accessibility programs in Science, Technology, Engineering, and Math, including enforcement of anti-discrimination protections for minority scientists

Protestors at Space Needle on Friday, March 7 (Photo by Arjun Kumar)

Chetan Seshadri, a tuberculosis researcher at the University of Washington, described the NIH funding cuts in material terms. He’d initially declined the speaking invitation from the rally organizers until the NIH grant review panel he was scheduled to participate in was abruptly canceled.

“We’ve been told it’s about budgets,” he said. “If it was about budgets, they wouldn’t have canceled my nonrefundable flight.”

Seshadri pointed to the NIH’s proposal to cap indirect costs on grants at 15% as particularly impactful for researchers. For example, the University of Washington doesn’t own the building that houses his lab and instead pays rent through a high indirect cost rate. The proposed change to indirect costs would lead to an estimated $90 million loss for the university.

The UW secures more federal research dollars than any other US public university. Now, with grant funding withheld and grant review panels canceled, Seshadri said he’s worried about making payroll for his lab.

Many of the cuts to federal agencies are being challenged in court. Washington Gov. Bob Ferguson expressed his support and described lawsuits the state has joined. He expressed confidence in the ongoing lawsuits, pointing to his record as the state’s Attorney General when he won 58 cases while losing 3 against the first Trump Administration. That line drew cheers.

Stand Up for Science in Seattle. Mar. 7. (Photo by Kelsey Woodruff).

A look at the audience, however, revealed mixed support for the Washington Governor, who has proposed $4 billion in cuts to the state budget after inheriting a deficit. Signs like “Bob focus on the revenue” and “Furloughs are BAD for Science!” criticized the governor’s proposal to furlough state employees (including public university workers) to address an estimated $15 billion state budget shortfall.

In a nod to conservatives, pediatric oncologist Jim Olson of Seattle Children’s Hospital described growing up and “pulling himself up by the bootstraps.” He finished college in three years while simultaneously working and being supported by federal Pell Grants for low-income students. Olson earned his MD/PhD at the University of Michigan (again with the support of federal funding) before becoming a leading researcher of brain cancer in children.

Federal research funding fueled his work, and it eventually translated into his co-founding of three biotech companies — Presage Biosciences, Blaze Bioscience, and Link Immunotherapeutics. Those companies collectively raised over $200 million in venture capital and created dozens of high-paying jobs.

Government and industry each have roles to play, Olson said. Government, he said, “is intended to do what companies cannot do” – including supporting the training of young scientists.

Jim Olson, professor, Seattle Children’s Research Institute; program director, Invent@SC

Many such trainees have felt heightened anxieties because of these cuts. I ran into a friend, a first-year graduate student, who was rotating between professors to choose a permanent lab. There aren’t many choices, as few professors have enough funding flexibility to accept a new student.

As a third-year graduate student working on immunotherapies, my own collaboration with the National Cancer Institute has also been effectively frozen, first by a ban on external communication from the Department of Health and Human Services and then by cuts to the NIH’s intramural research funding. Each of my classmates has a similar story.

Many people were sharing their stories at the protest. An estimated 4,200 people attended the Seattle event alone, with sister rallies in over 30 U.S. cities and several other countries.

Kelsey Woodruff, a graduate student and one of the rally’s organizers, noted the event came together in just three weeks. She joined the organizing effort after feeling disillusioned with government and federal funding, saying “the rally felt like a place to put my frustration and anger in a productive way.” Woodruff wanted to “restore a sense of agency” and remind her fellow scientists and allies that “you can keep advocating for science and calling your representatives.” In a time when many feel powerless, she said this rally was one way to “feel like you can do something about it.”

Such advocacy was new to many scientists, with the recent turmoil inspiring them to write to their legislators for the first time.

But trying new things is itself a practice of science. As Seshadri said, “the founding fathers were scientists – political scientists – who tried something new. They didn’t know if it would last, and it’s now being put to the test.” The current administration, he said, “wants people to give up and look away.” It was time for people to “use their voice and speak truth to power.”

Arjun Kumar is a graduate student in Molecular & Cellular Biology at the University of Washington who participated in the rally.

5
Mar
2025

Sluggish Corporate AI Adoption Has Motivated Entrepreneurs To Pick Their Spots 

David Shaywitz

As economic historian Carlota Perez has described, there is typically a significant time lag between when the promise of novel technology begins to emerge and the productive deployment of this technology at scale; TR readers will recall the discussion here from June 2023.

Today, we are seeing this with generative AI, an emerging technology that everyone is still trying to get their arms around (see this TR discussion).  The inevitable uncertainty associated with these early days has hardly discouraged large consulting firms, who have all developed “AI playbooks” and are busy persuading potential corporate clients that they are lagging their peers in AI and risk impending extinction. 

A Cautionary Tale From Big Pharma

Nevertheless, meaningful (vs performative) adoption of generative AI with most large enterprises has been predictably sluggish (see this TR discussion from August 2024).

Ziv Bar-Joseph

Ziv Bar-Joseph, the former VP-Head of R&D Data and Computational Sciences at Sanofi, candidly and generously shared on LinkedIn lessons learned from his recent experience at the large French pharma. These takeaways include (emphasis added):

– Pharma moves slowly. It takes over 10 years to develop a drug. So its not surprising that planning and decision making at big pharma can look very long and frustrate potential partners (and our own employees). Some of it is just bureaucracy. But much of it is intentional. These are often decisions that will have long lasting impact and its important to get them right.

– Adoption remains a major challenge. Not because of any principled objection to AI or new technology. But rather because it is very hard to change the way people work. Other issues affecting adoption of new technology are changing needs, people leaving and change in priorities and focus.

–  Sanofi is not an AI company. While it continues to develop cutting edge AI tools, Sanofi would prefer to purchase or partner rather than build AI products internally.  This makes economic and business sense. But it can be frustrating for our internal teams, especially when the decision comes after internal work already started on a similar product (usually because at the time we started the external solution was not available).

These findings are neither unique to Sanofi nor likely to shock regular TR readers. Yet Bar-Joseph’s insights emphasize a real challenge faced by the field: how to most effectively leverage AI when it’s brutally difficult to meaningfully implement AI in large corporations at a non-glacial time scale.

Don’t Make The Tool – Implement It

One answer that seems to be emerging – at least among impassioned AI investors – is to identify focused and more manageable opportunities (vs transforming a giant pharma corporation) and drive the AI mediated change yourself.

Cass Mao, a Silicon Valley tech entrepreneur, wrote recently on LinkedIn:

I know 10 different people leaving venture investing right now to do a PE [private equity] play with AI.
The basic thesis being: more opportunity than ever right now to drive value in SMB [small and medium sized businesses] using technology. But adoption is slow, super fragmented market, a ton of competition with 100s of new tools launching every week.
“Easier” to buy a small company, drive adoption, and reap rewards via direct ownership of the bottom line – a few million in personal upside within a few years.
vs. be deploying capital in the fast moving froth, high vals, high churn, high competition. so many tools funded and fighting the distribution war, competing with similar tools to seek adoption.
you’re seeing tools that cost $20/month eliminate **tens of thousands of dollars of cost**.
better to be the SMB with 50 different ways to save $30,000, than one of 50 SaaS cos charging $240/year.

In short, she’s suggesting that:

     (a) Cheap AI tools can save a significant amount of money if deployed effectively and in the right context;

     (b) If you can identify the right opportunity (basically a job amenable to your tool, and a small organization where you can actually implement the technology), you can do better implementing the AI yourself and pocketing the revenue from the efficiency gains vs trying to sell a particular AI tool in a very crowded market.

The question, of course, is how (or whether) this can be applied to biopharma.

Consider the following approach, suitably anonymized, but inspired by a real techbio example (there are probably a number of startups trying something similar).

Let’s say you’ve identified a specific, valuable aspect of drug development where you believe your technology (AI or something else) gives you an economically valuable competitive advantage. You might believe, for example, you have a more efficient way of running clinical trials. Such a company might then seek to in-license clinical-stage assets from pharmas, execute efficient clinical development past a value inflection point, and then out-license the further de-risked assets back to pharma at a higher valuation. 

The basic strategy itself isn’t particularly original, and startups, with conviction around one asset or another, in-license molecules all the time. The difference in this case is that because you believe your technology allows you to prosecute assets more efficiently, you focus on leveraging this perceived advantage, ideally by raising sufficient money (from entranced tech VCs, say) to fund enough shots on goal. 

Through your superior efficiencies of clinical development, you hope, you have a high chance of clinical, and hence financial success. (You, and especially your tech investors, may also hope your technology allows you to identify more promising assets than skilled drug developers alone, though I’m still very skeptical about this part.)

Beware of Pyrrhic Technological Victories

The success of this type of approach will depend, of course, both on how well the technology works and how much of competitive advantage it actually delivers – does it really move the needle for the tech-enabled company? 

Consider this example from genetics: metabolism of the blood thinner warfarin is strongly influenced by two genes, CYP2C9 and VKORC1. Genetic testing can determine whether you are likely to be a “fast” or “slow” metabolizer. Yet, utilizing genetic testing turns out to offer at best minimal advantages to the traditional clinical approach of “going low and going slow,” to arrive empirically at a therapeutic dose. Thus, while it might seem in theory that genotyping technology could improve care, in practice, most doctors haven’t embraced it because the impact seems less than the aggravation.

Similarly, techbio companies need to be sure both that their technology really works and that it imparts a meaningful advantage. It’s a tough ask, but one that’s clearly attracted the interest of both investors and entrepreneurs who are convinced about the promise of AI in biopharma and are intensively pursuing the highest-leverage place in which to deploy it.

4
Mar
2025

Flashback: Q&A on Founding TR

[Dear Readers: This Q&A from the Knight Science Journalism at MIT blog on Feb. 3, 2015 captures my thoughts on founding TR and where biotech was going. Thank you for your support. — Luke ]

By Wade Roush

For writers, part of the fuss about the Web explosion of the late 1990s was that it was finally possible to cut out the middlemen. Blogs meant you could reach readers immediately and directly, without all the usual apparatus of the commercial media—editors, publishers, advertisers, circulation managers—getting in the way.

Reprinted with permission of Knight Science Journalism Fellowships at MIT.

3
Mar
2025

A Woman in the TechBio Arena: Najat Khan on The Long Run

Najat Khan is today’s guest on The Long Run.

She is the chief R&D and chief commercial officer of Salt Lake City-based Recursion. The company is one of the first-generation companies that have sought to reinvent drug R&D from the ground up with automated technologies that collect a lot of biological data and then analyze that data with AI algorithms. Some call this approach TechBio or industrialized drug discovery or engineered biology. The basic idea is to make drug discovery faster, cheaper and to improve the probability of success.

Najat Khan, chief R&D officer, chief commercial officer, Recursion

Longtime listeners may want to go back and listen to Recursion co-founder and CEO Chris Gibson on The Long Run in May 2022, as he talked about the company’s origin story.

Najat joins Recursion now that it has a much bigger pipeline of drug candidates to test its founding vision. She has a variety of experiences in healthcare and drug discovery. She previously worked to integrate AI applications into the R&D operations at Johnson & Johnson, where she was chief data science officer and a senior vice president overseeing portfolio strategy. She has a wide range of experiences across the R&D enterprise, at both large and small companies.

This is an extremely hard challenge. Despite some of the breathtaking advances in AI of late, we will not be getting magic bullet cancer drugs popping off the AI assembly line anytime soon. A lot of thoughtful work needs to be done first to set up the platforms right, and to chip away with incremental advances at various bottlenecks along the R&D continuum.

Najat is one of the people in the arena, so to speak, who understands the range of challenges and is humble about what it will take to get the job done.

Now before we get started, a word from the sponsor of The Long Run. 

This is a message to drug hunters who are up for a challenge. Are you ready? Here it is: there’s a new prize competition to spur discovery of drugs targeting TBXT. It’s a transcription factor involved in a number of cancers. The competition is offering more than $500,000 in prizes to investigators or companies who identify potent TBXT binders. The great part is that you only need to come up with the compounds; the competition organizers handle biophysical evaluation of submitted compounds. All the resulting data is returned to you confidentially. And you keep all IP rights.

TBXTchallenge.org

And, some of you have seen that I’m celebrating the 10th anniversary of Timmerman Report.

Reaching this milestone has gotten me thinking about my various activities, and that includes The Long Run. My friends at The Linus Group helped craft a survey so you can provide me some feedback on what you like, what you don’t, and what you’d like to see more or less of from this podcast. It only takes 5 minutes, and if you complete the survey, you will be entered with a chance to win one of three complimentary annual subscriptions to Timmerman Report (a $199 value). 

Complete the survey

Now, please join me and Najat Khan on The Long Run.

24
Feb
2025

Rewiring, Not Retiring: Health and Innovation for the Vanguard Generation

David Shaywitz

Most of my columns tend to focus on the importance and difficulty of applying emerging technologies to biopharma R&D, aiming to accelerate the delivery of impactful medicines to patients. 

Yet, as long-time readers know, I have an enduring interest in how to sustain health and ward off illness, a discipline that’s sometimes called Preventive Medicine, Preemptive Health, or, the term I prefer, Functional Longevity. 

Over the years, I’ve examined what it takes to make behavior change last, explored the role of technology and health coaches in tackling obesity, shared my own weight loss and maintenance experience, and looked at the discovery and impact of the GLP-1RA’s.  I’ve discussed the limitations of existing digital fitness platforms, which seem disproportionately focused on helping the young and fit stay young and get fitter.

I’ve examined how corporate wellness programs have struggled to evolve, often failing when interventions are implemented in isolation rather than part of a holistic strategy (as British scholars Michael Kelly and Mary Barker have thoughtfully discussed).  Similarly, I’ve reviewed the disappointing results of an ambitious behavior change study, while continuing to emphasize that we still must proceed with hope rather than cynicism. 

I’ve also talked about the often elusive promise wearables offer to provide deeper health insights, and the challenges encountered by “Quantified Selfers.” 

At the heart of all these explorations is agency – your confidence in your ability to influence the world and positively shape your health and environment.  Most recently, I’ve considered how AI might enhance personal agency and improve health. 

The Vanguard

Of the many opportunities within functional longevity, one stands out: the inadequately served needs of a demographic I think of as the “Vanguard.”  These are folks (like me) who are over fifty and grew up in an era of personal technology affording unprecedented agency.  They’ve torn up in disgust the AARP membership card they were sent when they turned 50. For them, 50 isn’t an inflection point — it’s simply a continuation of the dynamic, engaged life they’ve always lived and intend to keep living. 

They are tech-savvy and highly engaged but also face unique challenges. Reading tiny text on a screen and interacting with clunky interfaces isn’t always seamless, and their expectations for fitness and social spaces often differ substantially from twentysomethings. But they aren’t retreating to the sidelines — they expect products and services designed for their reality and are ready to engage with those who take them seriously.

I see in this demographic a profound opportunity to enhance health, not just manage decline — focusing on movement, connection, purpose, and agency to extend healthspan without the hype of extreme longevity fads, miracle pills, or fringe biohacking. It’s about real, evidence-based innovations that help the Vanguard move better, think sharper, stay engaged, and live with purpose.

Venture investors, particularly those in the Valley, are famously obsessed with youth. Many tech VCs adore and pursue young founders, despite the considerable success that more experienced founders have achieved, as Ali Tamaseb has so thoughtfully discussed in Super Founders, and as Ben Cohen highlights in a recent WSJ column. 

The result? A flood of products built by young founders, for young users, leaving those older than fifty overlooked, underserved, naively caricatured – and often all three. It isn’t so much age bias as it is market blindness. This disconnect has created a massive gap in innovation — and a profound opportunity for those willing to meet the Vanguard where they are.

The Vanguard isn’t aging out — they’re leveling up; they’re rewiring, not retiring.  They need entrepreneurs who see them, meet them, and take them where they want to go.

This is one of the great unmet needs of our time — and an extraordinary opportunity for entrepreneurs, investors, and innovators ready to design, build, and deliver the future the Vanguard expects – and deserves.

24
Feb
2025

Defend Young Scientists

Luke Timmerman, founder & editor, Timmerman Report

Biotech thrives on the creative dynamism of young scientists. Always has.

Young scientists are under pressure. NIH grants are on hold. If the NIH budget is gutted, and a generation is forced to find other ways to earn a living, then the biotech industry will lose.

It might not be clear for the next couple of quarters or next couple of years. But inevitably, if fewer people pursue careers in science, biotech companies will find it harder and harder to find qualified people to do the work.

Biotech should stand up now to defend the next generation of scientists.

Young scientists have been feeling the squeeze for some time. They earn starvation wages for years as graduate students and postdocs. Grants from the National Institutes of Health are so competitive, so hard to get, that the average age of a first-time R01 grant winner is past the age of 40. This makes it difficult for students, postdocs, and early career scientists to stay in the game long enough to someday pursue the dream of an independent research lab with a stable source of funding.

Nobody said science should be cushy. Scientists should expect to work hard on worthy problems to earn support from taxpayer-funded grants. But these barriers to entry are too high. It discourages people from entering science, or sticking with science when times get tough as they invariably do.

People in their 30s are often at the most creative, most productive stage of their scientific careers. This is the time to be optimistic and ambitious. It’s the time for making some of the big choices in life — what career to pursue, where to live, who to marry, how to save up to someday purchase a home.

The thrill of discovery will always be a draw. But our society chooses the extent to which we support it. We can choose to whack government science budgets and systematically devalue work at the National Institutes of Health, National Science Foundation, and other agencies. If we do, it would be familiar to what we have already done with humanities fields like visual arts, literature, theater, and journalism. Our culture largely steers young people away from these career paths, knowing that these jobs don’t pay well.

We shouldn’t allow this to happen to science, especially at such an auspicious moment in time.

Consider the opportunities in advanced biologics. We are in the early phase of a cell and gene therapy revolution.  It’s a source of competitive R&D advantage of the United States. That ought to translate into a competitive advantage for manufacturing. Jobs in this industry come with good wages, good benefits, and good career growth potential. They can also be a source of pride and dignity – no small thing.

There’s reason to think there could be a lot of these jobs in the next 10-20 years. More than 1,000 Investigational New Drug (IND) applications for cell and gene therapies are on file with the FDA. There were 1,975 clinical trials for cell and gene therapies at the end of 2024, according to the Alliance for Regenerative Medicine. Most of the product candidates in those trials won’t turn into new FDA-approved products, but some will. Some will be big.

Jobs will have to be created in specialized, customized manufacturing plants for cell and gene therapies. Advanced biologics like bispecific antibodies, antibody-drug conjugates, and targeted radiopharmaceuticals are here today, and bound for growth. Many of these medicines could be Made in the USA. There are national security reasons, national competitive advantage reasons, logistical shipping reasons, and workforce development reasons to keep most of this work on US soil.

There are large swaths of the map outside of San Francisco, New York and Boston where this work can be done relatively inexpensively.

Biotech – at least its more established and profitable players — could choose to invest more in internship programs, apprenticeships, and public/private partnerships with states to develop the workforce needed to make these things.  

Cultivating people over the long term will require a shift in mindset. Like any profit-driven industry, biotech isn’t in the business of creating jobs for the sake of creating jobs. It pays to be prudent when making new hires. It’s logical to want people to be ready to hit the ground running. In a harsh, risk-averse investing climate like we’ve had the past 3-4 years, it’s essential for many companies to hunker down and think about how to get through just the next few quarters.

For those able and willing to think a little more long-term, however, there’s an opportunity to reconnect biotech with the public. By standing up loud and proud for young scientists, biotech can become a symbol of individual career advancement, national economic prosperity and a healthier future for all.

Biotech can be the source of hope and optimism. It can be a symbol of the American Dream, much like how heavy manufacturing played that role in the Midwest during the 20th century.

It will require extending a steady hand to young people. It will require taking chances on people who might not otherwise get one.

We should invest more in science education. We should invest more in cutting-edge research at our universities. We should invest more in workforce development for an array of biotech jobs.

Investing in people for the future of biotech could even help rebuild some of the trust that has eroded.

Biotech should stand up for the next generation.

18
Feb
2025

Defend the FDA

Luke Timmerman, founder & editor, Timmerman Report

We need a competent, well-supported, tough and independent food and drug regulator in this country.

We need that independent cop on the beat so we can have confidence that the medicines, vaccines, diagnostics and devices at the core of modern healthcare have passed the scrutiny of an uncorrupted, scientifically grounded and ethical group of people working in the public interest.  

If the new Trump Administration wants to focus on cutting waste and the thicket of senseless bureaucratic rules and craft attitudes that slow down innovation, OK. If it thinks regulation might work more smoothly if drugs and food were under separate management, I’m listening. If it wants to ditch industry user fees, as long as the FDA budget is fully supported by citizen-taxpayers, that’s not a bad idea.

But if this Administration cuts so deep that the FDA can’t do its job, because it thinks only a fig leaf of regulation helps business interests, then we have a problem. 

We’ll have a Wild West of medicines being shilled online much like vitamin supplements based on unsubstantiated or false claims. If the budget slashers go too far, we’ll turn back the clock to the snake oil days that would make impossible medicine’s “first do no harm” credo.

That would be a terrible mistake. Biotech and pharmaceuticals are brimming with potential.

The FDA has always had a complex relationship with industry. It has had, and will always have, clashes with industry over how much evidence is necessary to approve a medicine, what the right safety–efficacy balance is for a given situation, or what a valid clinical trial design ought to look like to prove the benefits of a medicine outweigh its risks.

The FDA has always had critics. Always will. It will make mistakes because no one, and no agency, is perfect. But at a high level of budgetary policy, the problems at FDA stem more from being understaffed than from being overstaffed.

The agency has been underfunded and neglected through its history. Members of Congress and Presidents don’t win elections on abstract ideas like maintaining a safe and effective supply of medicines, vaccines, diagnostics and medical devices. The agency is mostly invisible, operating in the background.

Big budget increases haven’t come from members of Congress. In the 1990s, AIDS activists were furious over the bureaucratic bottleneck that caused new drug reviews to drag on for more than two years on average. Those patient advocates banged on the door and demanded the FDA review new treatments for AIDS as if their lives depended on them.

That activism paid dividends. It led to the Prescription Drug User Fee Act of 1992, which has been renewed every five years since. That law created the user-fee structure that speeds up drug reviews, and which now delivers about half of the FDA’s $7.2 billion annual budget.

Questions

In the midst of reassessing the consistently underfunded FDA budget, we should be asking some hard questions:

  • How much of the agency’s budget should come from user fees? How much is too much?
  • Does the FDA have enough people to regulate the current and coming tidal waves of biomedical innovation?
  • Can it efficiently handle hundreds of new applications for cell and gene therapies, which are more complicated to evaluate than typical small molecule pills?
  • Does it have the facilities and updated high-tech equipment it needs?
  • Does it have credible leadership capable of hiring great people and inspiring them to fulfill the agency’s mission?
  • Will the new commissioner be capable of communicating the nuanced value of the FDA to Congress, the President, and the public?

In the spirit of bold, ambitious thinking about re-imagining government that’s more efficient and accountable to the citizens, I’d like to propose a few ideas to reimagine and improve the FDA.

Move out of Washington, DC. The FDA doesn’t need to be in Washington. The FDA has almost 20,000 employees. Not all are in Washington, but many are. Scientific review teams can do their jobs anywhere, and it might be best to do the job in a quiet place free from excessive influence from Congressmen, the White House, or industry lobbyists.

By moving the FDA out of Washington, the federal government could find some budget savings. The FDA has valuable land that could be redeveloped by private developers of mixed-use business and residential properties. FDA could take the proceeds and build an integrated campus in the middle of the country on cheaper land.

How about Wichita, Kansas (pop. 390,000) or Tulsa, Oklahoma (pop. 411,000) or Milwaukee, Wisconsin (pop. 561,000). These cities offer relatively lower living costs and high quality of life. They have diverse demographics with White, Black, Hispanic and Native American populations that closely reflect the population of the country. The FDA, operating down the street from healthcare providers in a place like this, could test promising  initiatives in a “real world” healthcare setting.

Done right, the FDA could gain valuable insights into how to operationalize things like telemedicine for clinical trials, remote patient monitoring, and more efficient ways to gather a range of data types from genotype to phenotype. These initiatives could modernize the clinical trial enterprise.

By doing what it does differently, and better, the FDA could speed up drug R&D and lower the cost of what it takes to develop a new medicine. It could do that without undermining safety, and in a transparent way that builds back public trust in biopharmaceutical R&D.

FDA workers could put down roots and be good scientific citizens in their communities. They would be parents of kids in local schools, and neighbors to ordinary people.

Double the budget over five years while reducing user fees. The FDA has always had to struggle for resources. When it succeeds, no one notices. When it screws up, it’s headline news. The FDA doesn’t get to bask in the glory of discovery like the NIH. Its public health mission sometimes puts it crosswise with powerful constituents, like drugmakers or tobacco companies or Big Agriculture. The FDA doesn’t have a lot of natural allies in Congress who understand or enthusiastically support its multi-faceted work. Its budget, at $7.2 billion for 2025, is small potatoes for an agency that regulates one-fifth of the US economy. How is it supposed to monitor manufacturing facilities and supply chains around the world to keep us safe from contaminated or counterfeit medicines?

For more than 30 years, the agency has long been kept on a tight leash in Congress and has been forced to rely increasingly on industry user fees. Almost half of the FDA budget—$3.5 billion a year—comes from these fees that companies pay for the agency to review applications.

That’s one way to save a few taxpayer dollars. But it also creates a financial dependence on industry, and a closeness that can sometimes get a little too close in ways that are subtle and hard to quantify. I think there’s a place for user fees in the FDA budget, much like we pay user fees to visit National Parks. But the lion’s share of the agency’s budget ought to come from us, the taxpayers. Robert F. Kennedy Jr. isn’t entirely wrong to question this arrangement, although he goes too far in making broad-brushstroke claims of corruption.

With so many groundbreaking biopharma products coming down the pike, the FDA needs double the budget just to keep with the anticipated demands on this overstretched agency.

Pay Attention to the New Commissioner. The FDA acting commissioner since Jan. 24 is Dr. Sara Brenner. She’s an agency veteran, a physician and a public health advocate. She has deep experience in the diagnostics group at FDA and worked on the COVID-19 response. That might make her a short-timer in the role, as there are still plenty of hard feelings in the public about the way the pandemic was managed.

At a moment when the agency needs to restore public trust and break out of some of limited thinking of the past, it needs a commissioner with excellent communication skills and a vision for a 21st century FDA. The next FDA commissioner needs to communicate to the public and advocate passionately with leaders on Capitol Hill and the executive branch. Scott Gottlieb was skilled at this part of the job and understood how to strike the balance of protecting public health while facilitating quality development of new products.

Marty Makary

I’m thinking of someone to lead the FDA who has public health experience, who believes in the FDA mission to the bone, who can communicate scientific risk / benefit equations to a Nobel laureate or your grandma, and who doesn’t have too many industry conflicts.

Dr. Marty Makary of Johns Hopkins University is the nominee from President Trump. He’s a physician and a health policy expert. He has written guest editorials in major news outlets and appeared on FOX. He’s written bestselling books. He was critical of government policies during COVID. I haven’t interviewed Dr. Makary, but his qualifications for the job appear solid. I would like to hear him outline his vision for the FDA in front of the Senate.

Get Ahead of the Trends with PDUFA VIII. The Prescription Drug User Fee Act, the governing compact that has set the terms of engagement between industry and FDA since 1992, is renewed and updated every five years. The current iteration of PDUFA is due to expire in September 2027. It may seem far off, but behind-the-scenes negotiations between industry and the agency often take more than a year. The industry and agency will have to discuss fundamentals like fee rates, support for new initiatives, and allocating resources to keep up with the agency’s mission. It’s not too early to think about a new bargain.

Besides the need for more staff, there’s always a need to stay current with information technology, and lab technology tools, to keep up with an industry that is well-funded and moving faster than ever. The agency also needs resources for staffing up far-flung field offices so it can adequately do facility inspections, especially with the vast array of generic drug facilities around the world and the boom in biologic manufacturing here and abroad.

If we don’t make this investment, we can expect a slowdown in new product approvals—an abundance of innovations that can’t get all the way to people. It would be an “innovation pile-up” reminiscent of a Third World country.

If we’re smart, we’ll invest now to get ahead of the curve.

A visionary and well-funded FDA could consider master protocol study designs that could cut down on some of the inefficiency that bogs down many clinical trials today, like legalese in informed consent forms or slow Institutional Review Boards that are inconsistent from site to site. There are too many small, single-site, investigator-sponsored studies—small and crappy trials that never yield clear-cut answers. The FDA is the one agency that can take the lead on demanding new standards.

It’s easy to overlook the FDA. It’s easy for companies, investors, journalists and former FDA people to criticize. Often, we’re right when we do. It needs our scrutiny, our tough, independent and fair-minded questioning.

But the FDA also needs our support. It deserves our most creative, constructive ideas on how to fulfill its mission. We shouldn’t take it for granted. The pharmaceutical industry wouldn’t be worth much if the FDA were to wither on the vine.

We can’t allow that to happen. I don’t think it will. Let’s revitalize the FDA, and put it in position to be great at what it does for the next 100 years.

17
Feb
2025

Zero-Toll Medicine: How Individuals Can Use Crypto and AI to Fix US Health Insurance

D.A. Wallach, general partner, Time Bioventures

The U.S. health insurance system is stupid, immoral, and infuriating.

It is time to get rid of it altogether and replace it with an intelligent, modern, and efficient infrastructure befitting the American people and the 21st century.

Incrementalism is not the answer. Solutions that add further fragmentation and complexity (including Medicare Advantage, Accountable Care Organizations, delegated managed care, and integrated managed care) ultimately obscure the need to burn it down and start afresh.

I propose a different model which I’m calling “Zero-Toll Medicine.” It starts by leveraging advances in AI and blockchain technology to deliver health insurance free of toll-taking intermediaries like private insurance companies and Pharmacy Benefit Managers.

Zero-Toll Medicine aims to put patients in control of their own healthcare spending, eliminate vast amounts of administrative cost and complexity, and drive far more efficient market-based competitive pricing. It is rooted in libertarian and socialist idealism alike, exploiting the virtues of decentralized decision making and markets while realizing the civilized goal of healthcare as a fundamental right of American citizenship.

Why Do We Have Health Insurance?

Insurance exists primarily to pool risk. We do not know at birth who will require substantial medical care over his or her lifetime, but we can be certain that many of us will. And as the philosopher John Rawls argued, we should design our society such that we would be OK being born into any particular lot in life, since none of us chooses his or her circumstances at birth. Pooling our resources to guarantee basic medical care to everyone no matter where we’re born or how our lives unfold should be uncontroversial given our enormous societal wealth.

Limits on this commitment must arise from the fact that medical care can be very costly. We are unlikely to agree as a nation to cover unlimited care for every individual without regard to how much longevity or happiness it might buy. Therefore, rationing or “managing” the amount of care is inevitable. Furthermore, we cannot be held hostage to medical care at any price, and so should desire that medicine exist within the market economy, subject to competitive forces that optimize supply via price signals.

These three goals: 1) risk pooling 2) rationing care and 3) competitive pricing, are in theory the functions of our existing insurance system. But it fails at all three.

  1. Risk Pooling: The current US healthcare system fails to pool risk efficiently because, unlike in other insurance markets, we (rightly) prohibit insurers from discriminating on the basis of pre-existing conditions, or pricing policies on the basis of individual risk (apart from generic characteristics of a patient like geographic location and age). In principle, if health insurance companies had the ability to discriminate, they could generate profits from careful underwriting and risk prediction. But in our system, they effectively must cover any patient who signs up. Furthermore, if we seek to maximally spread out costs, we should have the largest risk pool possible, one that includes everyone – people who are healthy and people who are ill and need more costly healthcare services. Our current system, by contrast, splits the population into thousands of smaller risk pools, among them: employees of individual companies (self-insured employer plans), poor people in each state (Medicaid plans), retirees (Medicare), and so forth.
  2. Rationing Care: US healthcare fails to ration care ethically because this rationing is largely done at the insurance plan level. Pre-authorizations, claim denials, and benefit design are managed by plans, which amounts to their “playing doctor.” This is not a job that insurers are qualified to do, and they do not do it well. Moreover, evidence-based medicine demands that a “standard of care” dictate what care is appropriate and medically necessary, and this standard should be universal vs. varying arbitrarily across different insurers. The care that is appropriate for a patient has nothing to do with who insures them.
  3. Competitive Pricing: Our system fails to drive optimal competitive market pricing and supply because it aggregates both supply and demand into oligopolistic blocs and removes decision-making power from the actual providers and users of care. On the demand side, each insurer effectively becomes a representative of tens of thousands of patients (and their employers, who hire plans and bear costs). On the supply side, large health systems and private-equity-financed provider roll ups are increasingly the counterparties in price negotiations. In other words, large insurance companies negotiate against large providers to set prices. None of these prices is transparent to the patient, making it impossible to shop around for the best deal.Unfortunately, this means relatively little true competition exists on either side. In many geographic areas, there are only one or two dominant healthcare providers where all the patients have to go. These providers therefore have tremendous leverage when negotiating with insurers. If a plan wants to operate in that geographic market, it has little choice but to ultimately contract with these health systems and take the prices on offer.

The dominant healthcare provider networks often negotiate opaque “omnibus” pricing schedules with insurers. Specifically, an insurer will contract with a health system for the full range of its services – surgeries, inpatient stays, hospital-administered drugs, etc. The insurer will be optimizing to minimize its overall expected costs, and the provider will be optimizing to maximize its overall expected profits. This means that different payers negotiating with the same provider may end up with very different prices for the same services. In other words, the same product (say, a joint replacement) will have a different price depending on the patient’s insurance company.

This excessive complexity begets excessive administrative operations. Many people are employed to do these jobs, managing the billing process. Every time a patient comes in for a service, providers have to figure out who is insuring the patient and what the negotiated price will be for that insurer. Then the provider will need to bill that payer for the service and manage collections. In several states, including California, if you go to a hospital, you will discover that the anesthesiologists, physicians, and hospital itself are all different commercial entities, each with its own contracts with your insurance company, tripling the administrative billing apparatus required to get paid for your care. If this seems like it doesn’t make sense, that is because it doesn’t.

Subsidizing Subsidies

What I have described so far are failures of our employer-based private insurance system, which covers just over half of Americans. The other side of our system is public insurance, which covers 36% of the population in total. Among those publicly insured are 93% of those 65 and older (Medicare), 36% of children (Medicaid), and 16% of working-age adults (Medicaid). Others are covered by the Veterans Administration and state programs.

The public system is itself a patchwork of government and private entities. For example, Medicaid is run by the states, but outsources substantially to private insurance companies in what are known as MCO arrangements (managed care organizations). Similarly, Medicare is run by the federal government, but a majority of beneficiaries now choose Medicare Advantage plans, which are also outsourced plans run by private insurers. Even Traditional Medicare (the original plan that is managed by CMS and not outsourced) outsources its claims processing and assorted functions to 12 “MAC”s (Medicare Administrative Contractors), privately-owned and somewhat mysterious vendors that also engage in care rationing across Medicare patients (for advanced diagnostics, as one example).

% of US Population Insured by Insurance Type. Source: U.S. Census Bureau, Current Population Survey, 2023 and 2024 Annual Social and Economic Supplements (CPS ASEC).

 

While there are imaginable efficiencies derived from these outsourcing arrangements, you can be sure that there is also a lot of graft and toll taking. If the government lacks discipline in spending taxpayer money, private companies one further layer removed are often even less scrupulous.

This is particularly true if there is little competition for these contracts. To take one well-publicized example, Medicare Advantage plans have pressured physicians they control to overdiagnose patients with chronic diseases in order to receive larger payments without delivering correspondingly valuable incremental care. The entire premise of Medicare Advantage is in fact questionable insofar as the government pays plans a premium beyond typical Medicare costs to manage each patient. The last government MedPac estimate is that we are spending $83 billion more than we would in Traditional Medicare to cover Medicare Advantage members.

In spite of this waste, Medicare and Medicaid still pay artificially low prices to care providers. And the majority of hospitals, including all non-profit hospitals, must accept these prices in order to qualify for their tax exemptions. The result is that many providers serve public-insurance patients at a financial loss and therefore need to make up for it (i.e. overcharge) their private insurance patients. Private-insured patients provide an enormous subsidy for public-insured patients. In fact, private payer prices are oftentimes negotiated explicitly as multiples of Medicare rates. This also drives a perverse incentive for hospitals to manage their “payer mix” in favor of patients with private insurance. While many hospitals take seriously their obligation to the common good, it is simply a fact that their financial health is imperiled if they take care of too many poor people.

The subsidies run in the other direction, as well. Since employer-based insurance is a tax-deductible expense, all taxpayers are subsidizing private insurance. And as economist Uwe Reinhardt pointed out, since employer-based insurance is a form of compensation, the deductibility of these premiums amounts to a regressive tax policy because the tax avoided by high wage earners (on “insurance compensation”) would have been at a higher rate than the tax avoided by low wage earners.

In short, employers subsidize public-insured patients, taxpayers subsidize employer-insured patients, and we redistribute wealth from lower to higher income workers in the process. These convoluted cash flows make it exceedingly difficult to calculate precisely who is getting screwed most.

The short answer: it’s all of us.

Radical Simplification

A smart and modern healthcare system would achieve the following goals:

  1. Enable every American citizen to afford a satisfactory level of medical care
  2. Ensure that medical care is evidence-based and transparent
  3. Create robust competition among healthcare providers and pharmaceutical companies to win the business of patients, driving efficiency, patient experience, and innovation

Decentralized ledgers and smart contracts, technologies originated in the cryptocurrency industry, enable a new model of American healthcare capable of meeting these goals with a radical new open insurance and payments system, “Zero Toll Medicine” (ZTM).

Here are the building blocks of this system:

  1. A new, open blockchain protocol, ZTM, on which every US citizen and healthcare provider would have a wallet. This wallet would function as a bank account specifically for government-funded healthcare spending and receipts.
  2. A minimal federal government health insurance agency, which could replace CMS. This “agency” would primarily comprise a computer codebase governing its interactions with the ZTM protocol and participants but would inevitably require some number of staffers to manage activities in which human judgment is unavoidable.
  3. A ZTM stablecoin pegged to the US Dollar.
  4. A library of composable smart contracts enabling programmable payments in the stablecoin.
  5. A computer-readable standard of care.

The aim of this system would be to directly fund patient wallets when they require basic medical care, and to enable them to shop and directly pay providers and product manufacturers for this care with no insurance companies, PBMs, or other intermediaries. The system would also allow patients to further fund their wallets with their own money (or supplementary insurance payouts) in order to spend it on services and products beyond basic care.

Basic Care

The term “basic care” is of course ambiguous and loaded. There is no alternative but for the country to determine what level of care it deems worth covering for every person, and this is a political and ethical decision, not a technical matter.

“Basic care,” then, amounts to whatever care can be paid for with the country’s total public health insurance budget divided by the number of its citizens, with the caveat that spending would end up unevenly allocated according to individual patient needs (as with payouts for all insurance).

In 2023, our country as a whole spent an estimated $4.9 trillion on healthcare. And at that year’s level of taxation, the federal government took in about $4.5 trillion of total revenues, of which it spent roughly $2 trillion on Medicare and Medicaid. In other words, the government currently covers about 40% of our total healthcare budget and employers/employees cover about 60%. That latter 60% is misleading since, again, taxpayers subsidize healthcare costs through the tax deductibility of employer-sponsored premiums and subsidies for exchange plans (Obamacare), to the tune of $300 billion per year.

In other words, we currently socialize about 50% of total healthcare spending while employees bear the remaining 50%. I say that employees bear that share because the premiums their employers pay on their behalf would otherwise be paid to them as wages.

If we were to eliminate employer-sponsored insurance, then, 1) wages would go up, 2) government revenue would go up since these incremental wages would be taxed, and 3) employees would be left without insurance, but with more income available to pay for their healthcare needs out-of-pocket.

Assuming healthcare spending remained constant, and all incremental tax revenue went to public healthcare spending, the 50/50 split between socialized and privatized healthcare cost-bearing would remain the same.

With the government covering 50% of costs but expanding coverage to all Americans (not just those currently covered by Medicare and Medicaid), we could only afford to cover a level of care substantially lower than that supported by Medicare today. It would be fairly simple primary care services for all. But as Amy Finkelstein and Liran Einav point out in their excellent book, Medicare today is “Cadillac” health insurance and represents a dubious choice society is presently making to give the elderly sterling coverage instead of providing everyone with basic coverage.

The latter should be our goal, and the level of this basic coverage can be increased should we wish to socialize more than 50% of health spending. I personally would advocate something more like 70-80% of cost coverage for everyone (members of Congress enjoy 72%), but the redistributive implications of such a choice would depend on the tax strategy funding it and are difficult to project. Ultimately, society as a whole pays for 100% of healthcare costs, so the share borne by the public sector is simply a matter of how much we choose to insure each other vs roll the dice on our individual future costs.

As Finkelstein and Einav also argue, basic care should begin with foundational primary care for every citizen. Today, we spend a mere 5% of our healthcare budget on primary care. Spending more on primary care for everyone could deliver cost savings by helping prevent costly chronic illnesses. This is one area in which higher spending is likely warranted and could bring down overall costs. The paradigm of preventive medicine requires investing in the health of patients before they are sick or injured, and like education, pays off over long periods of time and in diffuse, difficult-to-calculate ways.

In today’s private-insurance model, the frequent movement of patients between insurers (typically when they change jobs) disincentivizes investment in primary and preventive care since its payoffs are assumed to be too far in the future to generate an ROI. Moving to a public insurance model eliminates this irrational short-termism.

Zero-Toll Medicine would engage each citizen as a stakeholder in the healthcare costs of the entire society, and could provide direct incentives for individuals to proactively invest in their health. For example, each year, every citizen could receive a payment to cover annual primary care costs. When the individual spent this on a wellness exam, labs, etc., he or she could receive an automated tax credit of an amount sized to drive maximum compliance. Various other “gamification” mechanisms could be considered to drive this sort of virtuous behavior at scale.

Bundled Stablecoin Payments

Beyond primary care, patients would receive so-called “bundled payments” sized to cover the projected reasonable costs of basic care for most conditions or needs. In a non-acute context, patients would receive a diagnosis from their primary care physician, and this diagnosis, entered into the ZTM protocol, would instantly trigger a bundled payment to their wallet corresponding to the “episode of care” associated with it.

For those unfamiliar, an episode of care is a concept utilized in today’s so-called “value-based” healthcare models and describes a set of medical services and products required to treat a condition over a pre-determined period of time. For example, if a patient needs a joint replacement, an episode of care covering this could encompass pre-surgery appointments, the surgery itself, the medical devices used in the surgery, post-surgical doctors’ appointments, and physical therapy services for a couple of months. A “prospective bundled payment” would be a payment made prior to all of this care that is sufficient to pay for it.

Bundled payments are today utilized in a variety of insurance models with the goal of aligning incentives between those who pay for healthcare and those who deliver it. The majority of insurance arrangements today remain “fee for service,” wherein providers bill insurance for each individual service and product they deliver. Many have concluded that this incentivizes over-delivery of care by rewarding providers when they rack up as many charges as they can, and bundled payments arose as a means of setting a fixed budget for an episode of care.

These episode of care models typically allow providers to profit if they are able to treat patients for less than the budget, generally by letting providers pocket the difference between their costs of care and the bundle amount. This can, unsurprisingly, create the opposite incentive, to penny-pinch on care and risk under-treatment. Compensatory payment structures are meant to overcome this by, for example, tying final “bonus” payments to measurable patient outcomes, so that docs maximize their profits only when they have rendered verifiably high-quality care.

In today’s value-based care models, this kind of incentive structure tends to flow downward from the ultimate source of insurance funding. Medicare Advantage plans, as the most prominent example, receive per-patient fixed annual payments from the government to manage the care of individuals who enroll in them. This amounts to their taking on the “risk” of those patients’ annual costs, since if a patient costs more to care for, the insurer will need to cover it, but will do so at a loss. They may then enter into agreements with physician groups or health systems to delegate this risk.

The aspiration of any of these models is that, ultimately, someone – a physician, a group of physicians, or an insurance company – will have a financial motive to be cost-conscious while taking good care of patients. Zero-Toll Medicine embodies the same logic but puts the power of value-based medicine in the hands of patients themselves!

Power To The Patients

Concurrent with receiving a bundled payment, the patient and their physician would also receive an automated report summarizing the diagnosis and the standard of care for treating it.

This report on the standard of care would clearly lay out for the patient the evidence supporting the recommended course of treatment and the projected itemized costs for obtaining this treatment, which would add up to the total bundle amount. Based on the location of the patient, the report would also generate a list of providers in the area, along with the prices they charge for the recommended services and the outcomes their patients have achieved in the past.

Based on this outcomes data, the patient could also receive a prediction of the range of outcomes they might expect, and the probabilities of these outcomes. Importantly, this report would also include information on complication rates and malpractice incidents associated with providers, empowering patients with visibility into the risk profile of the providers they consider.

The same framework would apply to pharmaceutical products. There would be no insurance plan drug formulary, no PBM, no rebates, and no convoluted discount networks. The patient would be free to choose among the drugs approved by the FDA and indicated by the standard of care for their condition, and could purchase these directly from a pharmacy or pharmaceutical manufacturer.

This would put patients in a position of power to decide where they want to spend their healthcare dollars, and would dramatically invert today’s hierarchy, forcing physicians and pharma companies to appeal directly to patients to win their business.

Furthermore, this model would lead to “one price for one product,” since each provider or product manufacturer would be competing in an open market for the business of millions of individual patients. Real price discovery would occur as patients determined where they could get the best value for their money, and attempts at predatory pricing would simply result in low sales.

Open Information

The model I’ve described can only work if information that is currently secret and siloed becomes public and open. This includes the prices that providers charge, which they have in the past brazenly refused to publish even when the federal government mandated it. More controversial than prices are data on the number of procedures doctors have done, complication rates, malpractice, and patient outcomes.

But Zero-Toll Medicine can drive this information sharing simply by requiring it of any network participant. For a hospital, physician, device company, diagnostic lab, or pharma company to receive payments through the ZTM system, an ongoing real-time “credentialing” process could be mandatory. Specifically, to be approved on the network, a medical provider would need to verify its qualifications to deliver specific types of care and then would need to feed into the network real-time data regarding patient outcomes to remain approved. This credentialing could likely be almost entirely automated.

Infinitely Programmable Healthcare

The most innovative aspect of Zero-Toll Medicine is programmability, which is uniquely possible with a crypto protocol. By programmability, I mean that smart contracts can be composed to endow payments with limitless custom logic. Some examples:

  • If a patient receives a bundled payment for a particular episode, those stablecoins could be made spendable only for a set duration of time, and on providers specifically credentialed for the associated services. This would prevent, for example, fraud in which a patient uses a payment intended for a surgery and spends it on cosmetic Botox injections over several years.
  • A provider like a hospital could take on an entire episode of care from the patient and commit to certain outcomes. The patient’s payment for this could be held in escrow until the patient or a 3rd party oracle on the network validated that the outcome was achieved.
  • Similarly, a pharmaceutical company could offer a drug on a pay-for-performance basis, giving patients the choice between a lower up-front price and a higher performance-based price which they only pay if particular outcomes are achieved.

It is worth mentioning that the volume of transactions and speed required to support ZTM may be infeasible with today’s incumbent “L1” blockchains. There are ongoing efforts, including Improbable’s Somnia, to create “gigachains” with sub-second finality and low enough gas costs to unlock this kind of highly scaled use-case.

Private Funding

These ideas merely scratch the surface of automated logic that could be deployed over the ZTM network. Practically, there would be two types of funds flowing through it: government insurance-funded stablecoins and patient-funded stablecoins. The latter would arise to the extent that patients desired to spend more on their healthcare than the government’s basic care budget would allow.

Say a patient required an inpatient surgery and the government bundle for this was only sufficient to cover a shared hospital room, the patient could put additional funds into her wallet to pay for a private room. This would result in a wallet balance comprising some amount of “public stablecoins” and some amount of “private stablecoins.”

Many benefits of this network, and most obviously comprehensive visibility into healthcare spending, result from having all healthcare spending take place on the network. And so a major question would be how to incentivize all private spending to be done on network vs off network.

One possible solution would be to make private spending tax advantaged. In the surgery example I used, a patient could fund private stablecoins into their wallet, and upon spending them on the surgery, would receive a tax credit or deduction. Again, programmable logic could determine what healthcare spending would benefit from this treatment: perhaps a private hospital room purchase would not but paying for a higher priced surgeon with better expected outcomes would.

There is precedent for this sort of tax-advantaged healthcare spending in today’s HSAs. But rather than deduct contributions to an account (saving), ZTM would only provide a tax benefit upon spending on qualified products and services.

From the standpoint of providers and manufacturers, payments received through the ZTM network would seamlessly integrate public and private funded stablecoins. And recipients could cash-out into USD at any time.

Finally, supplementary insurance could easily coexist with this model. Patients desiring additional coverage beyond the basic care government coverage could purchase plans independently. But these plans would pay out benefits directly to patients or into their ZTM wallets. The goal again would be to ultimately push all spending into the network, irrespective of its funding source.

Summary

Zero-Toll Medicine proposes eliminating America’s existing public and private insurance systems and replacing them with a programmable digital infrastructure for public insurance to cover all citizens, yet compatible with private spending, as well. This infrastructure would enable Americans to freely shop for their medical care with no intermediaries constraining the choices they could make.

By putting patients in control of all healthcare spending, ZTM would lead to maximally competitive market price setting and replace the oligopolistic and opaque pricing schemas that hamstring medicine’s affordability today. By allowing patients to decide what they value, prices would converge with patient demand, not the demands of today’s corporate intermediaries like insurers and PBMs who imperfectly represent patient interests due to their own financial incentives.

ZTM’s programmability would create a dynamic infrastructure for democratically-determined priorities and regulations constraining publicly-funded healthcare spending and allow instantaneous enactment of these rules. It would create total transparency around usage of healthcare products and services, the quality and cost-efficiency of this care, and its safety.

While such an ambitious revolution in our system is difficult to imagine, business as usual will bankrupt our country and continue eroding the public’s confidence in government and medicine. The sacred cow of healthcare reform efforts has unfortunately been our for-profit insurance industry, which extracts rather than adds value. It is high time to dissolve it for good and reclaim America’s leadership among advanced nations in the innovative provision of public health.

Postscript: Q&A w Peter Kolchinsky

My friend Peter Kolchinsky, founder of RA Capital, raised helpful questions in response to this essay. I share them below with my responses.

Peter Kolchinsky, managing partner, RA Capital

  • PK: What if the algorithm doesn’t allocate enough credits to allow someone to afford the nuanced approach that escaped codification in the algorithm?
    • DAW: The approach I’ve proposed would leverage existing ontologies for estimating the services and costs appropriate for managing a diagnosis. For example, DRGs are today widely utilized for inpatient care. In the value-based care industry, Optum Symmetry Groups and Prometheus Episodes could be useful starting points. Any attempt to regularize complex care paths will be imperfect, but it is likely that we could cover 80-90% of patient needs to start, and then build out more customized episode definitions or even bespoke episodes for less straightforward situations. The ZTM protocol could be programmed to give diagnosing physicians more or less discretion in charting a patient’s prescribed episode. Less time-bound chronic condition management could similarly be approached in a more bespoke manner, or broken up into renewable episodes of a year at a time, for instance.
  • PK: What if there are complications?
    • DAW: To receive payments on the ZTM protocol, physicians would need to report outcomes into the network, which would make them fully transparent. Patients, regulators, and others could directly view any provider’s complete history of services provided and corresponding outcomes. This would make it straightforward to generate comparative performance analytics on providers and products in real-time. Critically, complications and patient harm would become matters of public record. There could also be Amazon-like patient ratings for providers or individual services rendered.
  • PK: What if physicians judgement results in upcoding and issuance of additional credits that enrich the doctor?
    • DAW: As I mentioned in the essay, this behavior is currently a scourge on the Medicare Advantage market. While dishonesty will always be impossible to eliminate wholesale, ZTM would put physician diagnosis patterns into the open. Whereas today, this sort of fraud has been visible only to individual insurance plans or CMS, with ZTM it would all be publicly visible. De-identified patient characteristics (demographics, etc) could be viewable for a provider’s patient population and the provider’s diagnostic and prescribing behavior could be compared to that of other providers. Bots on the network could even be programmed by independent citizens to constantly look for fraud on the network, and win bounties when they found it.I have separately proposed the creation of a new category of labor that I call the “medical accountant,” which would in my “Streaming Medicine” model become the primary point of contact for patients. This individual would charge patients a flat annual fee like an accountant to be their sherpa through the healthcare system, and would use AI software to accomplish many of the functions of a primary care physician today. Any sort of complex or specialty care recommended by this individual would not redound to their financial benefit. Furthermore, patients could choose to cut this professional in on any benefits or bonuses achieved through the efficient management of their health.Any untoward behavior emerging in ZTM could be rapidly disincentivized and extinguished through the programmability of the network and the ability to modify the smart contracts conditioning any stakeholder’s payments.
  • PK: What use is the credit to a patient if they don’t spend it? Can they pocket the money?
    • DAW: The goal would be for patients to spend as little of their bundled payments as they can to achieve the targeted outcomes of the care the bundle covers. To incentivize spending as little as possible, any bundled payments that are not spent should benefit the patient somehow. I have proposed as one possibility that this could result in tax credits, but other incentives could be considered. As with capitated payments in today’s value-based models, this runs the risk of patients not taking care of themselves in order to get financial benefits. These incentives therefore would need to be contingent on patients actually purchasing the care they had been recommended, and achieving solid, measurable outcomes.This is a tough needle to thread, but all things considered, I believe that putting patients in charge of these decisions will work better than putting intermediaries in charge of them. Patients have the most at stake when it comes to their own health, so while they may behave irrationality, so too do physicians, hospitals, and insurance companies, to whom we entrust these sorts of choices today.
  • PK: What if patients don’t spend credits on prevention and get sicker and have to be issued more credits? Will we regret letting the patient make a poor choice that sticks us all with the cost? Maybe better to have just said “You should get this preventative treatment and we’ll pay for it…. if you don’t get it, then you lose out, you don’t get to keep any credits, and we’ll all be worse for it… in fact, can we pay you to go through with the preventative treatment?”
    • DAW: As with the previous question, tuning incentives to drive the behavior that is best for patients and society at large will be a constant challenge and opportunity. ZTM provides a framework for programmatically optimizing and evolving these incentives over time.

 

D.A. Wallach is general partner with Time Bioventures. See more of his writing and speaking on SubStack.