Coffee Break: The Powell Memo Kills American Science, Driving While Nonwhite Is Hazardous, and Science Can Recover but It Will Take Patience and Persistence.

Part the First: The Powell Memo started it all.  Written by Lewis Powell, then a Richmond corporate lawyer for Big Tobacco and later Supreme Court Justice, for the United States Chamber of Commerce, the Powell Memo set out how “to take America back” from the hippies and the freaks, Mario Savio, Abbie Hoffman, Tom Hayden, Charles Reich, the Smothers Brothers, and Ralph Nader included.  The Heritage Foundation is one of many busy children of the Powell Memo (i.e., Attack on American Free Enterprise System), and its Project 2025 has motivated the current President, through his minions, to fire government scientists willy nilly, terminate grants because their keywords are now politically incorrect (sex, climate, ecology, fossil fuel, disparities) and cancel long-term projects like the Diabetes Prevention Program Outcomes Study (so much for the importance of chronic disease to the current Secretary of Health and Human Services) because it has been run by Columbia University for the past several years.  Nature covers the story here:

The Heritage Foundation…released Project 2025, a policy guidebook and staffing list, in April 2023, as a blueprint for what it hoped would be a second Trump presidency.  Trump, however, disavowed the initiative during his 2024 presidential campaign, saying that he had no knowledge of it, after there was public backlash over the publication’s sweeping Republican policy proposals, such as banning abortion, overhauling the federal government and slashing funding for climate science.  But Trump and his administration have closely hewed to Project 2025’s agenda, detailed in a sprawling, 922-page book, passing executive orders to defund climate initiatives and target diversity programmes. The Wall Street Journal found that more than half of Trump’s executive orders (EOs) align with Project 2025 recommendations.  And most of its 40 listed authors are now key figures on Trump’s team.

Does the President know he is following Project 2025?  Asking for a friend.

Part the Second: Sometimes whistling silently past the graveyard during election season does not work.  One of Trump’s defenestrated is Dr. Peter Marks, who was longtime Director the Center for Biologics Evaluation and Research at FDA.  As the title puts it: Ouster of FDA’s Peter Marks alarms a biopharma industry that saw him as an ally.  Yes, I would imagine it does, even if Dr. Marks saw himself as something other than an “ally” of Big Pharma and Little Pharma:

When Robert F. Kennedy Jr., a longtime and visceral critic of pharmaceutical and biotech companies, was nominated by President Trump to be the nation’s health secretary, the head of biotech’s largest trade group issued a statement saying that he had “every confidence” that the industry would “continue to thrive and deliver” on its goals, and looked forward to working closely with the new administration.

Three months later, in February, when the National Institutes of Health announced plans to slash indirect cost payments to universities and other institutions that have received federal grants, the trade group, the Biotechnology Innovation Organization, issued no response, even though the work of those universities and other institutions is a critical driver of new drugs and other medical products.

On Saturday, one day after news that the Food and Drug Administration’s top vaccine regulator had been forced out of his post by Kennedy, who has since been confirmed by the Senate as health secretary, BIO CEO John Crowley released a statement saying that the group was “deeply concerned that the loss of experienced leadership at the FDA will erode scientific standards and broadly impact the development of new, transformative therapies to fight diseases for the American people.”

The historical contexts are incommensurable, but does no one remember Martin Niemoller or even Winston Churchill.  What goes around, comes around.  With a vengeance.  The foundation of Big Pharma is research supported by the National Institutes of Health and similar organizations.  Without a functional, even somewhat pliable FDA at times, nothing good from Big Pharma will ever get approved.  And that is the end of that story.  Things not so good getting approved?  A good bet.

The text of Peter Marks’s resignation letter is here.  It is one of the more remarkable documents of its kind, especially on MMR:

The ongoing multistate measles outbreak that is particularly severe in Texas reminds us of what happens when confidence in well-established science underlying public health and well-being is undermined.  Measles, which killed more than 100,000 unvaccinated children last year in Africa and…had been eliminated from our shores.  The two-dose measles, mumps, rubella vaccine regimen (MMR) using over the past decades has a remarkably favorable benefit-risk profile.  The MMR vaccine is 97% or more effective in preventing measles following the two-dose series, and its safety has been remarkably well studied. Though rarely followed by a single fever-related seizure, or very rarely by allergic reactions or blood clotting disorders, the vaccine very simply does not cause autism, nor is it associated with encephalitis or death.  It does, however, protect against a potential devasting consequence of prior measles infection, subacute sclerosing panencephalitis (SSPE), which is an untreatable, relentlessly progressive neurologic disorder leading to death in about 1 in 10,000 individuals infected with measles. Undermining confidence in well-established vaccines that have met the high standards for quality, safety, and effectiveness that have been in place for decades at FDA is irresponsible, detrimental to public health, and a clear danger to our nation’s health, safety, and security.

As you are aware, I was willing to work to address the Secretary’s concerns regarding vaccine safety and transparency by hearing from the public and implementing a variety of different public meetings and engagements with the National Academy of Sciences, Engineering, and Medicine. However, it has become clear that truth and transparency are not desired by the Secretary, but rather he wishes subservient confirmation of his misinformation and lies.

That will not leave a mark, alas.  One does wonder what the new Director of FDA, Dr. Marty Makary, formerly of Johns Hopkins University School of Medicine, is thinking right now.  Is he good with this?  Did he have no influence with the Secretary?  This will be revealed in due time.  I’m guessing he his on board with the destruction of American biomedical sciences, which will necessarily gut the nation’s first research university – Johns Hopkins.

Part the Third: Look to China for the next great things in biopharmaceuticals, therapeutic gene editing, and gene therapies.  This attack on American science will have consequences, as foreshadowed by Chinese advances in CRISPR therapy for Duchenne muscular dystrophy (DMD).  As U.S. efforts stall, China pushes ahead with CRISPR treatments for muscular dystrophy:

Two of the first efforts to treat Duchenne muscular dystrophy with CRISPR gene editing are getting off the ground in China, even as projects in the U.S. have seemingly stalled.

Trials for the fatal muscle-wasting disease were started in the last couple of months by two different Chinese companies. One, GenAssist, has already dosed one young boy. Huidagene, the other biotech, expects to dose the first of three boys soon and report data by Q1 next year.

The efforts are notable, as scientists and advocates have long hoped CRISPR could unlock a more powerful treatment for Duchenne than the technology used in Elevidys, Sarepta’s much-debated gene therapy. The need for such a treatment only grew last October, when trial results confirmed that Elevidys, while potentially useful, is far from a cure.

Would it be churlish to note that it has been ten years since Eric Olsen of University of Texas-Southwestern in Dallas showed that CRISPR could be used correct a genetic defect associated with DMD?  And that this result was so promising that Vertex Pharmaceuticals bought his startup company, Exonics for $245M.  Long live the Bayh-Dole Act of 1980!  But in fairness to all, delivery of any DMD therapeutic is a very difficult proposition because skeletal muscle is a very large target to cover, and the agent must remain active for a long time.  Liver is the much easier target for viral vectors.  Stem cells in the bone marrow even easier, if more dangerous because for that transplant to take place the entire immune system must be obliterated first.  Given current developments, it seems unlikely that US Science will remain up to the task.

What exactly does “Make America Great Again” really mean?  Which is not to say that the scientific establishment is above reproach, that the entire structure and mechanism is the best of all possible world.  An incremental approach can improve American science across the board.  But the “slash-and-burn” here is a solution to nothing, unless the goal is to destroy and rebuild from scratch.  Which is not possible.  From Links earlier this week: Xi Jinping is investing in China’s science and technology research as Trump is gutting America’s research foundations.

Part the Fourth.  Driving while nonwhite is a thing (not that we didn’t know this already). From ArsTechnica: Study of Lyft rideshare data confirms minorities get more tickets.

First: The data showed one thing clearly: Lyft has incentives for its drivers to avoid traffic violations, and they work. “Compared with the general population of motorists, our sample is less prone to speed, especially more than 10 mph over the limit,” the team writes. “As a result, our analysis examines only 1,423 citations for speeding.” While lower than you’d expect, that’s more than enough to do some statistics on the frequency of these citations.

Second: The results clearly reproduced a similar pattern to earlier research. Minority Lyft drivers were about 30 percent more likely to be pulled over and cited for speeding (the two analyses produced results of 24 and 33 percent). Once cited, they were also likely to receive higher fines, either 23 or 34 percent more than white drivers.

Third: The remaining question was why – the police could potentially be acting out of bias, or they could be attempting to deter minority drivers because they are more prone to problematic driving. So, the researchers compared the actual frequency of speeding based on the GPS data and used accidents as a proxy for problematic driving habits. Neither of these showed any significant differences between minorities and white drivers.

Diversity causing inequity and inclusion with malice aforethought?  Probably.  The article is published in Science.  Be sure to click on the “Authors Info and Affiliations” link on the landing page.  More leading universities getting themselves in trouble, again?

Part the Fifth. Slow Science could be the new Slow Food.  From The Conversation, Reliable science takes time. But the current system rewards speed.  Yes, it does.  I will violate Horowitz’s Law here, from my freshman sociology teacher: “Never let you own necessarily limited personal experience lead you to generalize, too far.”  But slow science is exactly right.  At its largest my laboratory had three PhD students who joined the lab in successive years, two high-level research coordinators with Master’s degrees, and a gaggle of undergraduates.  We published 3-4 papers in good journals in a good year.  That was enough.  The imperative to move fast means that you will inevitably break things, unintentionally or otherwise.  Another personal anecdote.  I was involved in a startup long ago as the person who actually knew how to do the protein chemistry necessary to produce the product.  That is until one day I pushed back with the question, “Why is there never enough time to do the experiment right but always enough time to do it over?”  Just as well.  I was long gone when the crackup resulted in several ruined careers.  From the article, much of this covered here before:

Lately, there have been many headlines on scientific fraud and journal article retractions. If this trend continues, it represents a serious threat to public trust in science.

One way to tackle this problem – and ensure public trust in science remains high – may be to slow it down. We sometimes refer to this philosophy as “slow science.” Akin to the slow food movement, slow science prioritises quality over speed and seeks to buck incentive structures that promote mass production.

Slow science may not represent an obvious way to improve science because we often equate science with progress, and slowing down progress does not sound very appealing. However, progress is not just about speed, but about basing important societal decisions on strong scientific foundations. And this takes time.

Unfortunately…

Much as with fast food, scientists are incentivised to produce as much science as possible in as little time as possible. This can mean cutting corners. We know, for instance, that larger samples lead to more trustworthy results because they are more likely to be representative of the relevant population. However, collecting large samples takes time and resources.

Fast science is also associated with gaming the system. As a hypothetical example, an educational scientist might collect data to find evidence for their theory that a new teaching style promotes better learning. Then, they look at the data and realise the intervention did not quite improve learning. But if you squint at it, there might be a trend if you drop a couple of pesky outliers that didn’t see a benefit. So, they do just that.

Final anecdote based on the above.  In my current life I have on occasion read the literature on medical education.  Suffice to say that if these scholars were studying the molecular basis of genetics they would still be arguing whether proteins (complex) or DNA (ATGC in sequence, simple) are the genetic material.

One thing I am proud of is that my primary professional home, The American Society for Cell Biology, led the way on DORA: Declaration on Research Assessment.  Will things come around?  One can only hope, without being particularly optimistic.

Part the Sixth: Leading scientists make a point while missing the larger point.  This Guardian article, More than 1,900 scientists write letter in ‘SOS’ over Trump’s attacks on science, is encouraging on the surface.  The letter is here.  For the most part it is forceful.  The signers are truly a Who’s Who of Science, many of them I know and admire.  But in my view they make a critical error with this sentence:

The quest for truth – the mission of science – requires that scientists freely explore new questions and report their findings honestly, independent of special interests.

Yes, the mission of science requires scientists to “freely explore new questions and report their findings honestly, independent of special interests.”  The problem is that too much of what the lay public sees as science is not “independent of special interests,” as the past five years have demonstrated.  Moreover, the mission of science is not “the quest for truth.”  The mission of science is to produce useful knowledge that leads to a deeper understanding of the natural world.  Science is provisional, always.  With truth, well that all depends.  This view has been presented here previously in Our Loss of Science in the 21^st Century and How to Get It Back, following the work of the philosopher Nancy Cartwright and her collaborators.

The “quest for truth” has something for all of us, and it has different meanings to the artist and craftsman, scientist, historian, theologian, priest, professor, philosopher, and the farmer, machinist, electrician, and plumber.  On the other hand, the quest for truth generally has little meaning for politicians and their acolytes, and their useful knowledge is entirely context dependent.

Corey Robin has a somewhat different take on this as he compares the scientists’ letter with one from the Harvard Law School faculty. The question of “truth,” perhaps?  Whose truth and for what?  In any case, the best way to alienate your interlocutors is to declare that you are righteously searching for the truth, while implying the opposite for them.  Corey Robin also asks Where is our tank man?  So far, nowhere to be found.

Part the Seventh: Snow leopards in the high mountains of Pakistan.  A mother and three cubs.  LiveScience is a bit cluttered for anyone’s taste other an internet ad sales rep but the animals are magnificent.

See you next week.