Guest Post: What a student pharmacist thinks about puberty blockers

August 29, 2023 • 9:30 am

Today’s post comes from Joseph Shen, a pharmacology student in Chicago. He has guest-posted here once before (see link below), and this week sent a contribution on what he’s learned about puberty blockers. I am not a pharmacologist and haven’t checked all the claims in this post, so please do so yourself if you have concerns. Also I am not giving any medical advice here and am not responsible for whether people decide to take or not take these drugs.

Shen is worried about the overuse of puberty blockers in “affirmative care” by doctors and therapists who don’t know about possible side effects of these blockers or the fact that they haven’t been tested properly for their effects on blocking puberty.

Finally, there’s a felid lagniappe to this post that I’ve put below the fold.

Without further ado (and see the “Update” at bottom.

What a Student Pharmacist Thinks about Puberty Blockers

Joseph Shen

He­llo readers, I have been on this website once before when Prof. Ceiling Cat (Emeritus) kindly shared my post about UIC’s mishandling of the Jason Kilborn controversy. What I didn’t mention at the time was that I am a pharmacy student. The ultimate role of the pharmacist is to optimize drug therapy, which means following best-practice guidelines, understanding side effects, and avoiding unnecessary therapies. You can see how this will connect to the transgender debate around puberty blockers.

I’m sure most readers here are familiar with articles giving critiques of puberty blockers like the one in the New York Times and the ones by Jesse Singal on his Substack site. While their content is good, I wanted to share with you how I viewed this topic through the lens of a pharmacist, focusing more on the drugs: what they are and how they are (mis)used. My goal is to inform you so that the next time you tell an affirmative care supporter that puberty blockers are not safe, they retort “what do you know about them?” or “why do you care that they need to be safe?”, you will have an answer.


Background Knowledge.

To understand drugs like a pharmacist, you must do a basic review of anatomy and physiology, specifically the hypothalamic-pituitary-gonadal (HPG) axis pictured here.

From Wikipedia

For anyone unfamiliar with this, the simplified version is that the hypothalamus releases gonadotropin-releasing hormone (GnRH) into the pituitary gland in front of it. The pituitary gland secretes two more hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH stimulates cells around immature ova and spermatozoa to help them mature. More importantly, LH triggers other cells nearby to synthesize progesterone, testosterone, and estrogens. This process triggers all the changes in puberty.


What, Exactly, are Puberty Blockers?

To block puberty, you have to interrupt the effects of the HPG axis. The most popular way is to inhibit the function of LH so that no hormones are synthesized. GnRH agonists are synthetic peptide molecules that mimic GnRH. They bind the same receptor and trigger the release of LH. At first, there is a release of LH and temporary increase in sex hormones. But after around 10 days, the stores of LH are depleted and desensitization reduces the number of receptors for GnRH, so releasing LH becomes harder. There are also GnRH antagonists: other synthetic peptides which bind the same receptors but don’t trigger any reaction, stopping the cycle immediately. While they work faster, these drugs are more costly and have more side effects, making them far less popular. When a person stops taking either class of drug, the HPG-axis resumes its cycles. This is what leads activists to claim that their effects are reversible. The cycles may resume on the molecular level, but that does not mean puberty will resume as normal on the bodily level.

Among GnRH agonists, just a few are used in most cases. Leuprolide is the most common drug in the class. It can be injected as a suspension into the muscle/fat every month, or it can be a biodegradable implant. Two other very similar drugs are goserelin and triptorelin, though they are available only as an implant and injection, respectively.

While known to the public as “puberty blockers” thanks to the controversy, GnRH agonists have several uses. They are first-line treatments for all stages of prostate cancer, depriving the tumor of growth-stimulating testosterone. They can also be used to treat endometriosis, in which uterine-like tissue grows somewhere else in the body, causing severe pain. Since that tissue is stimulated by sex hormones, GnRH agonists make it inactive. And during in vitro fertilization, a woman takes a dose to make sure she doesn’t ovulate early.

Notice anything about these uses? They are all either short-term or used to correct a hormonal abnormality. What GnRH agonists are not well-supported for using is stopping normal onset of puberty, leaving the body in a developmental limbo. Leuprolide, in fact, has a shady history. Its initial approval by the FDA was based on very limited data, with some small sample sizes and short durations. Some post-market studies carried out after approval also had issues, with serious side effects such as bone disease omitted from a 2010 study. The poor literature means we can’t definitively predict what will happen when you start and stop using the blockers. Human bodies going through puberty are not tardigrades that will hibernate when the environment is hostile and later restart as if nothing happened. Pausing puberty is more like pulling on a Slinky: leave it stretched too long—and it may never slink again. With no big longitudinal studies, we just don’t know.

The thing most people want to hear about GnRH agonists are their side effects, and there’s a lot to discuss. Mainstream articles frequently mention poorer bone health. Sex hormones trigger the cartilage known as the growth plate in the femurs to grow and then turn to bone. They also maintain a balance between bone growth and breakdown. For someone on puberty blockers, the growth plate may not mature, and the balance shifts towards bone breakdown, both of which make fractures more likely. Sexual issues are another real possibility. The lack of sex hormones can reduce or eliminate development of libido in both trans boys and girls. What I haven’t seen discussed is what happened to many girls who were given leuprolide for years to delay puberty so that they grew taller. Decades later, these girls who had normal puberties and who have never been on other treatments developed osteoporosis, weak joints, and fibromyalgia. What reason is there to believe similar cases won’t happen with trans kids without normal puberties? Beyond that, leuprolide and the others currently carry warnings for increased risk of heart attacks, dizziness and fainting, and a host of other conditions, all based on thousands of cases of reported adverse effects—how can these drugs possibly be perfectly safe?


A Pharmacist’s Concerns

It confuses me why all the debate over these drugs rarely involves pharmacists, who are the drug experts. Doctors may know treatments, but it’s pharmacists who are more keenly aware when a drug therapy is lacking evidence.

Improper prescribing is a huge, pharmacist-specific concern. Contrary to popular belief, pharmacists don’t just fill prescriptions made by physicians without question. Pharmacists are required by law to exercise “corresponding responsibility” and dispense drugs only when they’re safe and appropriate. I see the transgender controversy as having some of the biggest potential for improper prescribing. Without solid guidelines and with influence from various organizations like WPATH, pharmacists are put into a bind. We can either sign off on unwarranted med orders or refuse to fill them and be condemned by societal and professional peer pressure. We will have to stand up for our profession by saying NO when decisions are not based on good science. It is our duty to stop potential harm to patients, sometimes even if it’s what they want.

Another pharmacist-specific concern erodes trust in modern medicine. Physicians live by the Hippocratic Oath, often condensed into the phrase “first, do no harm.” At times, doctors withhold information from patients to spare them emotional and psychological harm (e.g., giving “affirmative” advice without telling parents so that they can’t be obstacles). This causes doctors to butt heads with pharmacists who, in contrast, live by the Oath of a Pharmacist [side note: the 2021-2022 updated oath includes the line “I will promote inclusion, embrace diversity, and advocate for justice to advance health equity.”] We tend to emphasize patient autonomy, being truthful, and giving enough information for them to make rational choices. It is unethical to deceive patients about a drug’s safety to increase the likelihood of using that drug. This kind of behavior makes practicing medicine seem like it’s based on reckless opinion rather than on evidence from clinical trials. When patients think their doctor’s suggestions are just opinions, then all they need to refuse a suggestion is their own opinion—the same kind of opinion that could make them refuse vaccinations or turn to alternative medicine.



This controversy would not exist if there was simply enough evidence. But we can’t do large-scale, longitudinal studies because they’re ethically and practically impossible. Subjects would have to be prepubescent and started on these drugs for years with consent from their parents. No thinking parent would allow this. Studying only children who claim to have gender dysphoria seems like the clear next option. But sample sizes would be much smaller, and the zealous proponents of affirmative care don’t want to wait years and delay transition. Observational studies are the best we can do, and we know their results so far are not promising.

I genuinely sympathize with the young, dysphoric people who are in a catch-22. If they use blockers but then lose their dysphoria, they may incur irreparable damage to their bodies for nothing. If they wait until they’re sure they want to transition, but their bodies develop, they may never be satisfied with themselves. But when I choose patient safety over satisfaction, I’m doing it not out of malice but because I care enough to value their wellbeing.

I apologize if this sounds like a polemic. While I speak from the principles taught to me as a pharmacist, I speak only for myself. I hope this piece was at least somewhat engaging and not as dull as the actual lectures we all had to sit through to learn this. I’ll end on a high note. As is customary for a cat’s staff member, I must share pictures of my boss. They tell a comedy in 3 acts.


One commentor (#9 below) correctly pointed out that I implied without evidence that physicians are frequently not discussing the risks of GnRH agonists with patients. This was wrong of me. What I should have written was that the medical field (at least in the U.S.) is largely supporting GnRH agonists regularly despite the lack of evidence for their safety, and not admitting to that. It is this air of support, not individual people, that concerns me. If and when individual physicians downplay the risks, then that is even more unethical; I’m certain that’s not the vast majority of doctors treating gender-dysphoric kids.

Here is the evidence for that support. The Endocrine Society (ES)’s 2017 guideline claims “pubertal suppression is fully reversible,” implying that long-term side effects are negligible. They “recommend,” (a strong statement) not “suggest,” (a weaker statement) that puberty suppression be used when indicated. They give a lukewarm review of the effects on bone and say next-to-nothing about brain development. Wikipedia conveniently lists the American organizations. that give position statements supporting GnRH agonists and/or the ES’s position. Position statements are not scientific evidence but carry scientific credibility in people’s minds.

This is exacerbated by mainstream media, in which articles from progressive-leaning venues (see here, here, and here) cite individual professionals who claim that puberty blockers are “well-studied, well-documented, and well-tolerated”, are “a benign medication”, and that the side effects are “not enough of a reason to allow a child … to continue going through puberty.” This small number of professional opinions (one of the lowest forms of scientific evidence) can shape what the public perceives to be the state of medicine. And again, it’s aways about what the doctors think in these articles, not the drug experts. Doctors are not always perfectly scientific and rational, needing pharmacists to help guide them with drug therapy. It’s just that no one in the media bothers speaking to a clinical pharmacist.

Guidelines are the starting-point resources for doctors before they make their own professional decisions. It is not a good thing when they hold poorly supported statements and when people are hesitant to challenge them because of social pressure. It is misleading at best and needs to be addressed with evidence and compassion, not instinctively calling critics transphobic.


[JAC: Read the story below the fold (click “

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An international group of gender-change specialists urges caution for American doctors and therapists

July 16, 2023 • 10:00 am

A bunch (21) of doctors and Ph.D.s from nine countries (Finland, the UK, Sweden, Norway, Belgium, France, Switzerland, South Africa, and the U.S.) published the following op-ed in Friday’s Wall Street Journal. It might be paywalled, so I reproduced the entire short letter below.

First, be aware that this, as noted below, was in response to a letter from the President of the Endocrine Society published recently, a letter that staunchly defends the efficacy of “gender-affirming care.” That care involves a combination of therapy and, nearly always, medical intervention through hormones. That letter, from Dr. Stephen Hammes, said this:

Roy Eappen and Ian Kingsbury’s op-ed “The Endocrine Society’s Dangerous Transgender Politicization” (June 29) ignores scientific evidence and the conclusions reached by the American Medical Association, the American Academy of Pediatrics and other reputable medical organizations. More than 2,000 studies published since 1975 form a clear picture: Gender-affirming care improves the well-being of transgender and gender-diverse people and reduces the risk of suicide.

If you already know the evidence, you’ll know that this claim is wrong: there is not enough evidence to form a “clear picture” of either well-being or suicide. In response, the signers of the letter below (not shown) took issue with Hammes’s claims.

Click the headline to read, but here’s the whold thing.  And I’ve put the important parts in bold:

As experienced professionals involved in direct care for the rapidly growing numbers of gender-diverse youth, the evaluation of medical evidence or both, we were surprised by the Endocrine Society’s claims about the state of evidence for gender-affirming care for youth (Letters, July 5). Stephen Hammes, president of the Endocrine Society, writes, “More than 2,000 studies published since 1975 form a clear picture: Gender-affirming care improves the well-being of transgender and gender-diverse people and reduces the risk of suicide.” This claim is not supported by the best available evidence.

Every systematic review of evidence to date, including one published in the Journal of the Endocrine Society, has found the evidence for mental-health benefits of hormonal interventions for minors to be of low or very low certainty. By contrast, the risks are significant and include sterility, lifelong dependence on medication and the anguish of regret. For this reason, more and more European countries and international professional organizations now recommend psychotherapy rather than hormones and surgeries as the first line of treatment for gender-dysphoric youth.

Dr. Hammes’s claim that gender transition reduces suicides is contradicted by every systematic review, including the review published by the Endocrine Society, which states, “We could not draw any conclusions about death by suicide.” There is no reliable evidence to suggest that hormonal transition is an effective suicide-prevention measure.

The politicization of transgender healthcare in the U.S. is unfortunate. The way to combat it is for medical societies to align their recommendations with the best available evidence—rather than exaggerating the benefits and minimizing the risks.

This letter is signed by 21 clinicians and researchers from nine countries.

There’s also a coda to this letter, which appears to be a kind of addendum (like a Supreme Court Justice’s partial dissent) coming from someone who may have been asked to sign the op-ed:

Transgenderism has been highly politicized—on both sides. There are those who will justify any hormonal-replacement intervention for any young person who may have been identified as possibly having gender dysphoria. This is dangerous, as probably only a minority of those so identified truly qualify for this diagnosis. On the other hand, there are those who wouldn’t accept any hormonal intervention, regardless of the specifics of the individual patients.

Endocrinologists aren’t psychiatrists. We aren’t the ones who can identify gender-dysphoric individuals. The point isn’t to open the floodgates and offer an often-irreversible treatment to all people who may have issues with their sexuality, but to determine who would truly benefit from it.

Jesus L. Penabad, M.D.

Tarpon Springs, Fla.

I agree with that letter, too. I would never ban transsexual medical treatment for those people old enough to make an informed decision (I’m thinking about 18 years old), but young people need objective therapy, not “rah rah—>hormones” therapy.  If a therapist prescribes puberty blockers for a young person on the very first visit (or worse, sends them to doctors prescribing gender-change hormones), that is not a good therapist.

Of course the solution to this dilemma is research, which is why several European countries have put puberty blockers into the class of “clinical experiments” and are starting to practice less “rah-rah: transition” therapy in favor of actually listening to children without instantly affirming their desire to transition. That’s especially important because the large majority of young people experiencing gender dysphoria (about 80%, I think), eventually grow out of it, often by simply becoming gay.  And being gay doesn’t run the risks of medical complications, sterility, and the inability to have orgasms: some of the side effects of hormone treatment.

And it would help if extreme gender activists would stop politicizing this issue. In all my years of writing on this site, I don’t think I’ve ever gotten such nasty and ignorant pushback as I have from gender activists who accuse me of transphobia simply because I think we need more research before we start injecting hormones into children and adolescents, lopping off bits of their bodies, and giving them objective rather than “affirmative” therapy. That view is not “fear of trans people”, for crying out loud. But the activists, who have ideology but not evidence on their side, resort to name-calling to intimidate their opponents. And it often works.

The pile-on also comes if one suggests, as did Abigail Shrier, that there can be social pressure that influences people to change their gender, a claim that by now I think is undeniable. (Adults, of course, are free to make their own decisions, but again, these should be informed decisions, and the long term effects, both medical and psychological, of transitioning are not often discussed. One reason is that gender activists rain down hatred on anyone who brings up these issues.)

In Friday’s Weekly Dish, Andrew Sullivan picked up on this letter and wrote about it, giving some statistics in response to the oft-heard claim made by some doctors and therapists advising parents of gender-dysphoric children, “Do you want a live boy or a dead girl?” That, of course, implies a very high risk of suicide by girls who aren’t allowed to transition to the male gender. Sullivan:

To give a sense of the bullshit, here’s Stephen Hammes, president of the Endocrine Society:

More than 2,000 studies published since 1975 form a clear picture: Gender-affirming care improves the well-being of transgender and gender-diverse people and reduces the risk of suicide.

Note the vagueness, and the absence of any mention of children — the only population we need to be concerned about. And here is the Endocrine Society’s own study on sex reassignments for kids:

We could not draw any conclusions about death by suicide.

Today, in the Wall Street Journal, 21 pediatric clinicians from nine countries call Hammes out. In those countries that have conducted systematic evidence-based reviews of all the studies involving children, all of them have concluded that “the evidence for mental-health benefits of hormonal interventions for minors [is] of low or very low certainty.” The risks — permanent sterility, inability to experience orgasm ever, irreversible changes to the body, voice and face — are very real. Yet the American Academy of Pediatrics refuses to conduct a similar systematic review, five years after its last guidance.

A survey of a decade of child transitions in the UK, from 2010 to 2020, found that the data “shed no light” on whether reassignment affects the suicide rate. But here’s the stunner: of the more than 15,000 children treated for gender dysphoria, the number of suicides was four. It is insane to believe that every child with dysphoria will kill themselves if not subjected to a sex change. If a doctor tells you this, find another doctor.

Why would they lie like this? I honestly don’t know. Here are some possibilities: misguided compassion for children in distress; believing you are part of a cultural revolution that starts with children; banking on the vast revenues of having patients for a lifetime of treatment; or just following ideological fiats, intimidated by woke peers, and fearing liability for past missteps.

I think that pretty much covers all the possibilities. I’m not sure why the U.S., compared to other countries, is particularly resistant to discussion of medical and psychological issues like this, especially given that this isn’t just an ideological discussion, but a discussion with medical consequences.  As far as I can see, we should be doing what the Europeans are increasingly doing about this issue: collecting more data.

The UK’s National Health Service bans puberty blockers for minors except for clinical trials; NYT reports it without mentioning potential physical harms of blockers

June 11, 2023 • 9:40 am

And with this decision, implemented on Friday (see NHS announcement below), the UK joins several other European countries—Finland, Norway, and Sweden—in removing adolescents’ access to puberty-blocking hormones except in clinical trials. This is clearly a significant decision given the UK’s previous reassurances, in the Tavistock Gender Centre, that puberty blockers were perfectly safe and reversible.

And this reassurance is still given all over America, too, conveyed to adolescents contemplating “stalling” puberty until they decide what to do. (Most decide to continue with the transition, going on to full male or female hormone treatment and/or opting fur surgery.)

But such assurances of safety and reversibility are not credible right now, for we just don’t have enough data to deem puberty blockers (used off label) as either “safe” or “completely reversible”. In fact, there are suggestions of some possible physical harms, harms that the NYT wrote about in both January and November of last year.  We won’t know for sure until proper clinical trials are done. Until then, it’s irresponsible to prescribe these drugs outside of a trial. And of course proper warnings and written assent of patients that they understand the warnings are essential.

Here’s what else is irresponsible: writing an article about possible harms of puberty blockers but mentioning only psychological harms, neglecting the physical ones. Click below  to see the NYT’s new article about this (and at least they covered it); I also found it archived here.

After in the article above, the NYT adds this about possible “harms” (they do say that the NHS “stated that ‘there is not enough evidence to support their safety or clinical effectiveness as a routinely available treatment’.”)

Background: Data on the effects of blockers is sparse

Last year, the N.H.S. announced that it would be shutting down the country’s only youth gender clinic after an external review showed that the Tavistock Gender Identity Development Service had been unable to provide appropriate care for the rapidly increasing number of adolescents seeking gender treatments. The clinic had seen a sharp rise in referrals, from 250 young people in 2011 to 5,000 in 2021.

Puberty blockers, which work by suppressing estrogen and testosterone, were first tested on children with gender dysphoria in the Netherlands in the 1990s. The Dutch researchers published their first study on 70 children in 2011, finding that the adolescents reported a decrease in depression and anxiety after taking the drugs.

But a British study of Tavistock patients published in 2021 showed that blockers had no effect on children’s scores on psychological tests. The study found that 43 out of the 44 participants later chose to start testosterone or estrogen treatments. One interpretation of the data is that all were good candidates for hormone therapy. But the numbers raised concerns at the N.H.S. about whether the drugs served their intended purpose of giving adolescents time to think.

“The most difficult question is whether puberty blockers do indeed provide valuable time for children and young people to consider their options, or whether they effectively ‘lock in’ children and young people to a treatment pathway,” Dr. Hilary Cass, the pediatrician overseeing the independent review of the N.H.S. gender service, wrote last year.

Note the absence of any mention that there’s more than psychological harm at stake, and the lack of any report that long-term physical harm hasn’t been properly studied.

But see this from the NYT article in January of last year:

Few studies have followed adolescents receiving puberty blockers or hormones into adulthood. Dr. Ehrensaft and others are now working on large, long-term studies of patients in the United States.

. . . Puberty blockers, for example, can impede bone development, though evidence so far suggests it resumes once puberty is initiated. And if taken in the early phase of puberty, blockers and hormones lead to fertility loss. Patients and their families should be counseled about these risks, the standards say, and if preserving fertility is a priority, drugs should be delayed until a more advanced stage of puberty.

. . .Experts in transgender health are divided on these adolescent recommendations, reflecting a fraught debate over how to weigh conflicting risks for young people, who typically can’t give full legal consent until they are 18 and who may be in emotional distress or more vulnerable to peer influence than adults are.

Here the article appear sto be talking about post-blocker treatment with male or female sex hormones.

Some of the drug regimens bring long-term risks, such as irreversible fertility loss. And in some cases, thought to be quite rare, transgender people later “detransition” to the gender they were assigned at birth. Given these risks, as well as the increasing number of adolescents seeking these treatments, some clinicians say that teens need more psychological assessment than adults do.

And here’s what the NYT said last November:

Dutch doctors first offered puberty blockers to transgender adolescents three decades ago, typically following up with hormone treatment to help patients transition. Since then, the practice has spread to other countries, with varying protocols, little documentation of outcomes and no government approval of the drugs for that use, including by the U.S. Food and Drug Administration.

But there is emerging evidence of potential harm from using blockers, according to reviews of scientific papers and interviews with more than 50 doctors and academic experts around the world.

The drugs suppress estrogen and testosterone, hormones that help develop the reproductive system but also affect the bones, the brain and other parts of the body.

During puberty, bone mass typically surges, determining a lifetime of bone health. When adolescents are using blockers, bone density growth flatlines, on average, according to an analysis commissioned by The Times of observational studies examining the effects.

. . .Many doctors treating trans patients believe they will recover that loss when they go off blockers. But two studies from the analysis that tracked trans patients’ bone strength while using blockers and through the first years of sex hormone treatment found that many do not fully rebound and lag behind their peers.

That could lead to heightened risk of debilitating fractures earlier than would be expected from normal aging — in their 50s instead of 60s — and more immediate harm for patients who start treatment with already weak bones, experts say.

“There’s going to be a price,” said Dr. Sundeep Khosla, who leads a bone research lab at the Mayo Clinic. “And the price is probably going to be some deficit in skeletal mass.”

So why didn’t the NYT emphasize, in its latest article, that some doctors think there are long-term physical harms that may come from blockers? That was, after all, one of the reasons why the NHS and other nations in Europe have limited their use to clinical studies. I can guess only that they don’t want to get into the messy (but necessary) details.

The NHS announced the policy taking effect in a curiously anodyne statement on “Implementing advice from the Cass Review“, referring to a scathing indictment of the Tavistock clinic by Hilary Cass, former President of  the Royal College of Paediatrics and Child Health).  Here’s the bit about blockers, with a link to more on another site:

We are now going out to targeted stakeholder testing on an interim clinical commissioning policy proposing that, outside of a research setting, puberty suppressing hormones should not be routinely commissioned for children and adolescents who have gender incongruence/dysphoria.

The purpose of the clinical policy is to formalise this commissioning approach and ensure there is clarity on the position by the time the new service providers begin seeing patients in the context of the new and final interim service specification. The interim service specification and the clinical policy, once finalised, come together to define the overall commissioned service.

NHS England has established a new national Children and Young People’s Gender Dysphoria Research Oversight Board which has now approved the development of a study into the impact of puberty suppressing hormones (‘puberty blockers’) on gender dysphoria in children and young people with early-onset gender dysphoria. More information on the Board and the study can be found in the consultation report.

The U.S. really should take these other countries’ decisions more seriously. Indeed, puberty blockers have been banned in ten U.S. states, along with a general ban on “gender-affirming care.” Those states are all Republican, and so the Democrats and gender activists have become enraged, deeming these laws “transphobic”. And indeed, perhaps an animus against trans people has motivated some of the laws’ stipulations, but I’m talking only about the bans on puberty blockers. Until we know more about them, it seems wise to do the clinical studies.  Yes, it’s possible and even likely that the blockers won’t erode mental health, and may even improve it in gender-dysphoric children, but mental health is not the only issue at stake.

Further, since about 70% of children diagnosed with gender dysphoria eventually grow out of it without hormone treatment, often becoming lesbian or gay, it also seems that we should hold off on these blockers and replace them with empathic (not “affirmative”) therapy. Given the high incidence of resolution without blockers, the possible medical damage, the lack of long-term studies, the fact that most children on blockers go on to full transition, taking sex hormones and sometimes getting surgery (a course that renders them infertile and often unable to achieve orgasms), and the unlikelihood of children as young as 10 or 11, when puberty begins, being able to make informed and irreversible medical decisions—all this makes me think that the U.S. should follow the lead of Europe: use blockers only in clinical trials until they’re proven to be safe (or unsafe).

That is not, of course, to say that children with gender dysphoria shouldn’t be treated. What they need until the age of consent for transition (I tend to favor 18, but your mileage may very) is good psychological therapy, not therapy in which the doctor eggs on children to take blockers and then become transsexual.  Good therapy is not just one or a few sessions with an explicit goal of transitioning, but listening to children and helping them work out their issues. If, at the age of consent, they still want to transition, by all means allow them to do so and support them.

The NYT seems to have a curious attitude toward puberty blockers. First it takes two steps forward, calling out their dangers, and then takes one step back, hiding their dangers.


UPDATE: For a stronger negative view of puberty blockers, see this WSJ op-ed.

The National Academies of Science, which issues reports on opioid use, took $31 million from the Sackler family, pharmaceutical gazillionaires who largely created the opioid crisis

April 24, 2023 • 11:30 am

The book below (click on the cover to go to it) is one of the best piecces of nonfiction I’ve read in a year. It details the story of the Sackler family, in which three Jewish brothers, the sons of immigrants, worked together to push opioids for pain relief, and not in an ethical way. They eventually devised Oxycontin and Oxycodone, marketing them (via the company Purdue Pharma) to doctors as a kind of safe cure-all for pain, in the meantime completely ignoring reports of widespread addiction and deaths. (They also covered their tracks but not going public about what they really did and by becoming philanthropists, always insisting that the name “Sackler” be prominently associated with their buildings and galleries.)

The lawsuits eventually began, detailed by Wikipedia;

By 2017, a series of articles linking the Sacklers to Oxycodone as well as a public campaign by photographer Nan Goldin to link the Sacklers to the opioid crisis, led to stigmatization of the Sackler name with many museums and universities refusing financial gifts from the Sacklers.

While the family was eventually sued, the Sacklers used their company to declare bankruptcy, link their personal finances to the fortunes of Purdue Frederick, and ultimately managed to escape any financial consequences at all. The family continued to maintain that they knew nothing about the abusive and deceptive marketing practices of the company and maintained the lie that their opioids were not addictive and that the few people who abused their drugs were already addicts to begin with.

Eventually, the Justice Department settled with Purdue Pharma for an $8 billion criminal and civil settlement and another $225 million from the Sacklers themselves.  Nobody in the family has faced criminal charges, and they’re still living like kings.

The book is a page turner, and well worth reading, but it doesn’t paint a flattering portrait of the Sacklers, who come across as an affable but nefarious family determined to get as rich as possible no matter how much damage they did to humans in pain.

Imagine my surprise, then, to see this long article in yesterday’s New York Times. It details how the National Academies of Science (NAS), a private organization (but partly funded by the government) took millions from the Sacklers at the same time it was producing reports on opioid policy in America. The NAS exists as a body of elite elected scientists and doctors whose job is to produce definitive reports to help steer U.S. government policy.  Even if the NAS said it wasn’t swayed by the donations to come up with favorable takes on opioids, this is one of the most arrant conflicts of interest I’ve seen in science. The NAS didn’t even divulge in its reports that there was a “potential conflict of interest.”  This has really made me depressed about the NAS, which is supposed to be free of commercial taint.

Click to read the article. And remember, even if the Sacklers didn’t influence policies recommended by the NAS, scientists are still required to disclose potential conflicts of interest no matter what. And why, I wonder, did the Sacklers give so much money to the NAS?

Some excerpts:

For the past decade, the White House and Congress have relied on the National Academies of Sciences, Engineering and Medicine, a renowned advisory group, to help shape the federal response to the opioid crisis, whether by convening expert panels or delivering policy recommendations and reports.

Yet officials with the National Academies have kept quiet about one thing: their decision to accept roughly $19 million in donations from members of the Sackler family, the owners of Purdue Pharma, the maker of the drug OxyContin that is notorious for fueling the opioid epidemic.

The opioid crisis has led to hundreds of thousands of overdose deaths, spawned lawsuits and forced other institutions to publicly distance themselves from Sackler money or to acknowledge potential conflicts of interest from ties to Purdue Pharma. The National Academies has largely avoided such scrutiny as it continues to advise the government on painkillers.

“I didn’t know they were taking private money,” Michael Von Korff, a prominent pain care researcher, said. “It sounds like insanity to take money from principals of drug companies and then do reports related to opioids. I am really shocked.”

Unlike the World Health Organization, which was accused of being manipulated by Purdue and later retracted two opioid policy reports, the National Academies has not conducted a public review to determine if the Sackler donations influenced its policymaking, despite issuing two major reports that influenced national opioid policy.

One of those reports, released in 2011 and now largely discredited, claimed that 100 million Americans suffered from chronic pain — an estimate that proved to be highly inflated. Still, it gave drugmakers another talking point for aggressive sales campaigns, primed doctors to prescribe opioids at an accelerating rate and influenced the Food and Drug Administration to approve at least one highly potent opioid.

Another problem arose in 2016, months after the National Academies received a $10 million Sackler family donation. The F.D.A. had tapped the institution to form a committee to issue new recommendations on opioids. But one senator took exception to some of the members selected by the Academies, complaining they had “substantial ties” to opioid makers, including Purdue. Before work began, four people were removed from the panel.

It’s a total disaster, and the NAS hasn’t even investigated whether there may have been a real conflict of interest, even though the organization took at least $31 million from the opioid-pushers and issued two reports about opioids, one of which has already been discredited.

A wee bit more from Lisa Bero, “chief scientist at the University of Colorado Center for Bioethics and Humanities”:

Accepting millions of dollars from the Sackler family while advising the federal government on pain policy “would be considered a conflict of interest under almost any conflict-of-interest policy I’ve ever seen,” Dr. Bero said.

Indeed. So what does the NAS say when caught with its pants down? They simply equivocate. This is NOT the NAS I know of:

Megan Lowry, a spokeswoman for the National Academies, said in a statement that the Sackler donations “were never used to support any advisory activities on the use of opioids or on efforts to counter the opioid crisis.” Ms. Lowry added that the organization had been prevented from returning the Sackler money because of legal restrictions and “donor unwillingness to accept returned funds.” The Academies declined to make senior officials available for interviews.

And there’s more:

Soon after the National Academies report was issued, Dr. Andrew Kolodny, president of Physicians for Responsible Opioid Prescribing, emailed the institution and asked whether it would disclose that Ms. Christopher’s organization [Myra Christopher was an NAS panelist whose own group took Purdue money] had received funds from Purdue.

This is another conflict of interest, for panelists have to disclose their own conflicts.

“No, sorry, can’t do that,” Clyde Behney, an official with the Academies, replied in an email in August 2011 reviewed by The New York Times. “Keep in mind that the report is done and released, so the future is more important than the past.”

Seriously?? What kind of bullshit answer is that?

In its reports, some involving panelists who took money from Purdue, the NAS never disclosed any potential conflicts of interest.

In the end, the NAS now has millions of Pharma/Sackler money that it can’t use. As the paper suggests, perhaps the NAS should emulate Brown and Tufts, who used their Sackler money to help alleviate drug addiction:

Given the devastation of the opioid crisis, Michael West, senior vice president of the New York Council of Nonprofits, said that it would be worth the effort for the Academies to follow their lead.

“This would be a way,” he said, “of trying to make it right.”

Never in my life would I have expected the august NAS to be so sleazy. It’s not just that they took the money and didn’t disclose it, but also that they’re now pretending they didn’t do anything wrong.

Paul Offit: Covid came from the Wuhan wet market

March 29, 2023 • 12:00 pm

Paul Offit is a pediatrician and infectious-disease specialized whose take on the Covid pandemic always seemed quite sensible.  He works at the medical school at the University of Pennsylvania and is also, according to Wikipedia, “a member of the Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee and was a member of the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices.” He’s done a lot of work on vaccines, has written several books about them, has gone hard after anti-vaxers, and is highly respected.  So when he weighs in on covid, we should listen.

The “conventional wisdom” now, promulgated by both the DEI and FBI, is that the virus came from an accidental release in a Chinese lab. But I’ve never been fully convinced by that—especially because they found the virus in the Wuhan wet market and the first cases occurred around that market.  But now Offit musters the evidence for the wet-market hypothesis, and it seems pretty convincing.

I’ve never understood why it’s become such a big deal about where the virus came from—unless for some reason you want to blame the Chinese government, but knowing the original source is helpful in giving early warnings of pandemics and working out how to stem them. A wet-market origin would lead to a very different strategy from a lab-leak origin.

At any rate, Offit just started a new Substack site called “Beyond the Noise“, and I read the first post, “Lab leak confusion,” out of curiosity. (It’s expensive at $80 per year, so I probably won’t subscribe, but the first read is for free.) I just wanted to summarize why he thinks the virus came from the wet market, and then you can argue it out among yourselves.

Click to read:

I’ll just give his list of arguments for the lab leak hypothesis (these aren’t “theories” in the real sense, they’re just best guesses):

He first describes the popularity of the lab leak claim, and then dismantles it thusly:

If you believe Carl Sagan’s statement that “extraordinary claims should be backed by extraordinary evidence,” this was an extraordinary claim backed by no direct evidence.

On the other hand, SARS-CoV-2’s spillover from animals to people in a wet market in Wuhan is supported by an abundance of evidence:

• Photographs taken of the western section of the Huanan Seafood Wholesale Market showed raccoon dogs and a red fox, both of which are known to be infected with SARS-CoV-2. A customer at the market, knowing it was illegal to sell certain wild animals, took these photos on December 3, 2019, and posted them on Weibo, a Chinese microblogging website. The photos were immediately deleted, but not before a CNN reporter was able to pass them on to scientists in the United States.

• In that same area of the market, SARS-CoV-2 virus was detected in carts, drains, a feather-and-hair remover, a metal cage, and machines that process animals after they’ve been slaughtered.

• The first known human case of COVID occurred on December 10, 2019, in a female vendor at the Huanan Market; two of the first three cases had direct contact with the western section of the market. Indeed, more than half of the early cases had direct or indirect exposure to the Huanan market. Wuhan is a city of 11 million people. There are probably 10,000 places where a new virus could have arisen. Nonetheless, the first cluster of cases were restricted to the western section of a market that was selling live animals susceptible to the virus, exactly where you would have expected a spillover event to occur. The estimated chance that this pattern had occurred randomly, and not as a direct result of animals infecting people, is about 1 in 10 million.

• The Huanan Seafood Wholesale Market is located north of the Yangtze River, about 9 miles from the Wuhan Institute of Virology, which is south of the river. If the pandemic virus leaked from the Wuhan Institute, it would have had to have leapt across the river without infecting anyone in between.

• The emergence of SARS-CoV-2 virus bears a striking resemblance to SARS-1 spillover events from animals to humans that occurred in Foshan Guangdong province in China in 2002 and again in Guangzhou, Guangdong in 2003.

And then the new evidence, which is quite telling:

• Finally, on March 17, 2023, a discovery by three prominent researchers, Michael Worobey, an evolutionary biologist at the University of Arizona, Kristian Anderson, a virologist at the Scripps Research Institute in California, and Eddie Holmes, a biologist at the University of Sydney, should have ended the controversy. Examining samples from the Huanan Seafood Wholesale Market first taken in January 2020, the international research team found genetic evidence for SARS-CoV-2 virus in raccoon dogs that had been sold illegally, further proving the origin of the virus.

If you’re into medicine, vaccines, or the debunking of quackery, you might want to subscribe.

h/t: Bat

NYT op-ed touts the power of dreams to help you make decisions

March 27, 2023 • 9:20 am

The link to this NYT came from reader Mike, who said, “I guess I won’t be the only subscriber sending you this article. [He was.] Serious Deepak Chopra vibes. I think it’s arguably worse than the Tish Harrison Warren opinion pieces because those are obviously religious. This one is stealthily religious, and comes with a “I’m a practical salt-of-the-earth science person” disclaimer. Disingenuous at best.”

Well, the piece does tout the useful power of woo, or rather of dreams, but I have to feel sorry for the author. Farris was diagnosed with breast cancer that had spread to the lymph nodes, and had radiation and a single mastectomy. Now she says she’s “NED” (“no evident disease”), but the waiting and waiting in cases like this must be awful, and could last a lifetime. Plus her radiation treatments apparently brought on heart disease, so she’s had a rough time. I want to avoid criticizing her, but do want to take issue with her view that her dreams were useful aids to making medical decisions.

Farris describes how she was was guided by her dreams when facing treatment options that, according to the doctors, were about equally efficacious. Because she’s still alive, she gives credit to her dreams as factors that helped her survive. That is the “woo” bit, and I don’t think the NYT should give people the idea that their medical decisions should be guided by their dreams—especially because dreams are often either bizarre or ambiguous.

Click to read:

Throughout her cancer treatment (including its first detection, revealed in a dream about two helicopters crashing on a highway), Farris responded to what she saw was the message of her dreams.  Here’s the way she decided to get chemotherapy when it was a judgement call:

Because my cancer is hard to see, often invisible on scans, the doctor told me it was likely to be even more advanced than my other doctors thought, but we wouldn’t be sure until after my surgery. “There are nearly equally good arguments for and against doing chemo,” he said. “What do you want?”

That night I had a dream of soaring above a garden full of light. I woke laughing with delight, but then my laughter turned ironic — who has ecstasy dreams about chemo? Still, I took what felt to me to be the dream’s advice. I started chemotherapy.

Note that there’s no clear message in this dream—a clue to what was might really have been going on (see below).

When faced with the option of having a single or double mastectomy, she opted for the single based on this dream:

This appointment was about my “choice” between a single and a double mastectomy, and between reconstruction and no reconstruction. Double mastectomy, she said, would mean a much lower chance of developing a new breast cancer.

But not zero. “My sibling had a double mastectomy and then had a recurrence,” I told her, “and since the doctors don’t regularly scan double mastectomies, the recurrence was nearly missed.”

She made a quietly compassionate face. I’ve learned to pay attention to doctors’ silences. However, I’d already made my choice, based on the first dream I’d had in months.

In my apartment, flames were creeping up the blinds and down the back of the couch. I had two jugs in my hands, though only one was full of water, which I threw on the fire. I went to refill both jugs, but when I returned, the fire was already out. And so, with some relief and a laugh at the strange ways dreams communicate, I decided on a single mastectomy. One jug was enough. I didn’t tell my doctor about the dream, but I did tell her about my decision.

When doctors found a suspicious sign later on, she was faced with the decision of whether to opt for more radiation. She did, based on a dream:

That weekend, while I struggled, I had my last and strangest breast cancer dream. I saw nothing, as if I was in a dark room. A man’s voice, inflectionless, American-sounding, said, “You must continue with radiation.” It was as if my subconscious was drained of all the symbols, the stories, the irrational desires and impossibilities. The only straightforward dream of my life.

I did the extra radiation.

At the end of the piece, Farris weighs science (which offered no clear-cut choice in her treatments) versus her dreams, and more or less sees them as coequal:

It doesn’t matter whether you “believe” in science — the earth is still round. But we are creatures who need something to believe in — stories and symbols to make meaning from a chaotic universe. Are dreams the flotsam of our waking lives, washed up on the shores of consciousness? Or are dreams, like pain, meaningful messages from our bodies?

Imagine my open, uncertain, freckled hands. There’s no conclusive evidence supporting either hypothesis. But when I felt betrayed by my own body, dreams gave me a feeling of meaningful connection to, and faith in, myself. I’m as grateful for that connection as I am for highly advanced medicines, and for the doctors who spend every day reckoning with the mystery that is cancer.

Well, I’m not sure I’d choose dreams or something numinous to believe in. Neither did Christopher Hitchens when he got throat cancer. As he wrote in his book Mortality,

“To the dumb question “Why me?” the cosmos barely bothers to return the reply: why not?”

His answer was that cancers happen, and he happened to be an unlucky victim. Yes, he had hope, but I don’t see that as “something to believe in” or a “symbol to make meaning from a chaotic universe.”  The idea that you need to confect something numinous or metaphysical to guide you is one that Farris made, but I can’t help but think that the NYT is somehow printing this article to tout the effectiveness of the spiritual—something it does quite a bit.

Now I wouldn’t tell Farris that I think her explanation was bunk. But I want to advance an alternative explanation for Farris’s using dreams as guidance for her treatment—one that doesn’t depend on thinking that dreams are somehow prescient or useful. You might have thought of this explanation as you read her piece. And it’s this: while she was sleeping, and perhaps dreaming as well, her mind kept turning over her alternatives and working away on making a decision, even if she wasn’t conscious of it.

We’ve all had the experience when we’ve forgotten something like a name, and, after trying to remember it, you just give up.  Then, suddenly, hours later, the name pops into your mind. What that says to me is that though you were not consciously trying to remember it in the interim, the neurons in your brain kept working away on the problem. 

That working may or may not be reflected in the contents of your dreams, since we don’t know how dreams work, but what is making the decision is the program in your brain. You wake up and that program has spit out a decision: get the radiation. Or have a single mastectomy.  Your choice may have had nothing to do with the dream, or it may have been reflected in the dream. For all we know, the dream content may be correlated with your unconscious musing, or it may not (some of her dreams weren’t obviously connected to her medical decisions). The dream, then, might be the correlate of a decision made without conscious reflection, not the “thing” that arose to help you make the decision.

Thus, I think Farris’s alternative takes on dreams, below, is insufficient.

Are dreams the flotsam of our waking lives, washed up on the shores of consciousness? Or are dreams, like pain, meaningful messages from our bodies?

Rather, the answer may be “neither.” The content of dreams often reflects what’s going on in our lives, but rather than see them as “meaningful messages from our bodies,” I’d say that Farris’s decisions were based on unconscious reflections in her brain. This, I think, is a more sensible interpretation of what she experienced than her thinking, as she seems to do, that dreams were interacting with the doctors’ indecisions to help her settle on a course of treatment. And of course, despite the title of her headline, there’s no guarantee that the dreams gave her the best advice—advice better than the doctors could give.  In other words, it’s not the dreams telling her anything, but her brain producing the dreams as a byproduct of its unconscious work.

The decline and fall of America’s medical schools

February 25, 2023 • 11:30 am

A reader this morning used ChatGPI write me an email saying that he didn’t like the “excessive” amount of antiwoke stuff on this website, and wondered if I had heard this from other readers. (Answer: almost never, though people may vote with their feet).  Although I informed him that I write about what interests me, and that right now in academia (and elsewhere in America) we’re in the midst of a “racial reckoning” that could completely change the nature of the country, I still felt bad—as I always do when someone tells me I write “too much” about this and that.  And that’s despite Rool #6, which says this:

6. Please do not tell me how to run my site.  That is, comments about “too many cats,” “too many boots,” “not enough biology,” “too much religion,” etc., are not welcome.  I provide content free of charge, and if you don’t like the mix of posts, you’re free to go elsewhere.  By all means take issue with what I say, but don’t argue about the balance of topics.

So, especially today, don’t leave comments agreeing with the reader (i.e., please abide by rule #6).

I’m disturbed enough that although I present this Tablet article, which is antiwoke (its theme is the ruination of America’s medical schools via DEI initiatives), I’m not going to say much about it. It’s free and you can read it for yourself by clicking on the screenshot. There’s a reason to be more concerned with the quality of doctors that is being turned out than with, say, experts on English literature or evolution, for a poorly trained doctor can do a lot of damage to people’s lives and health.

I will give a few excerpts below.

Most of this is about UCSF, a terrific medical school, which has implemented a stringent new DEI policy:

These race-first imperatives have now come to influence the research priorities of major institutions. Perhaps no better case study exists than that of the University of California, San Francisco (UCSF), an institution devoted exclusively to the medical sciences, and one of the top recipients of federal grants from the National Institutes of Health. Last May, UCSF took the unprecedented step of creating a separate Task Force on Equity and Anti-Racism in Research, which proceeded to make dozens of recommendations.

That task force builds on layers of prior DEI bureaucratic expansion, spanning nearly a decade. This programming includes the “UCSF Anti-Racism Initiative,” started after the summer of 2020, which established dozens of new institutional policies throughout the university, such as “evaluating contributions to diversity statements in faculty advancement portfolios.” The School of Medicine, meanwhile, has published its own Timeline of DEI and Anti-Racism Efforts, which documents such steps as adding a “social justice pillar” to the school’s curriculum and creating an anti-racist curriculum advisory committee.

The policies often promote an idiosyncratic and controversial understanding of concepts like diversity and racism. Through its Difference Matters initiative, the medical school created a document titled “Anti-Racism and Race Literacy: A Primer and Toolkit for Medical Educators”—which is filled with eyebrow-raising assertions. Racism, the guide asserts, “refers to the prioritization of the people who are considered white and the devaluation, exploitation, and exclusion of people racialized as non-white.” Anti-racism, meanwhile, involves directly shifting power from those who are white to those who are Black. “Anti-racism examines and disrupts the power imbalances between racialized and non-racialized people (white people), to shift power away from those who have been historically over-advantaged and towards people of color, especially Black people.” Of course, when applied to the allocation of lifesaving medical care, these ideals can carry weighty consequences. During the height of the COVID pandemic, New York, Minnesota, and Utah issued guidance for allocating monoclonal antibodies that heavily prioritized racial and ethnic minorities.

But race isn’t the only issue for which these initiatives demand action:

Some of these initiatives create obvious issues of academic freedom. In 2020, the UNC School of Medicine created a “Task Force for Integrating Social Justice Into the Curriculum,” issuing a report with dozens of recommendations. One called for faculty to adhere to “core concepts of anti-racism,” listing several of these required “concepts,” including “race is not a set biological category” and “specific organs and cells do not belong to specific genders.” The task force also called for students to “be trained in core advocacy skills”—even listing a number of political causes that it deemed important for students to embrace. These causes, which the report labeled “health realms,” included “restoring U.S. leadership to reverse climate change,” and “achieving radical reform of the US criminal justice system.” The school initially listed every recommendation as “On Time” on an online implementation tracker, though it eventually walked back some of the more controversial requirements.

Finally, UCSF’s (non)response to criticism:

By the time it published the report, the UCSF task force was aware of all of these issues. Each had been brought up by UCSF employees during the comment period. The comments were published in the report’s appendixes, which make up perhaps the most telling part of the whole publication.

One commenter repeated the same line in every answer: “I fundamentally do not feel or have ever felt that UCSF is a racist place. These are grossly misdirected funds and efforts.” Several cautioned against embracing discriminatory policies in the name of anti-racism. “All of the above sounds to me like trying to fight racism with more racism,” one noted. Still others urge the task force not to distract from UCSF’s focus on scientific research. As one commenter put it, “UCSF is a medical and life science campus. Its strength lies in its objective data-driven experimental approach. Qualitative and sociological research has no place at UCSF and no place in scientific medical research and will undermine UCSF’s reputation.”

Yet rather than addressing the concerns of the school’s employees, the report attacks them while presenting its authors as the real victims.

It is important to note that while many of the comments received were constructive and helpful, task force members were traumatized by a striking number of comments that denied the existence of inequities and racism, and others that minimized the burden that racism has imposed, particularly on Black Americans at UCSF.

The forward to the report quotes one of the task force co-chairs, Sun Yu Cotter, who adds:

It is extremely important to acknowledge the magnitude of the emotional labor and trauma that many of the Task Force members endured in doing this work, particularly during the public comment period. Not only are many of the Task Force members, especially our Black colleagues, encountering and navigating racism on a daily basis at work and outside of work, we are also volunteering our very limited time to dive into grueling work (the minority tax is real!). Then to be gaslit by some members of our very own UCSF community was very painful.

Take note. This is the future of American medicine.

I have no comment but to add that for obvious reasons we really need to worry about the politicization of medical schools, and also about the extreme lowering of standards that has gone with it.

h/t: Adam

A “miracle antibiotic” in the offing? New compound works against all multiple-drug-resistant bacterial strains, and also stymies the evolution of bacterial resistance

February 22, 2023 • 10:30 am

A new article from The Lancet reports the synthesis of an antibiotic that not only kills all drug-resistant bacteria that have been tested (in vitro or in vivo in mice), but also seems impervious to being rendered ineffective by the evolution of bacteria. If this works out in humans, it would be a terrific advance in medicine: an antibiotic that can be used on people whose infections aren’t treatable because the bacteria are drug-resistant (this is common in TB, for instance), but also an antibiotic that seems to be impervious to the evolution of bacterial resistance. It’s also easy to synthesize using organic chemistry, and can be easily tweaked in its structure just in case some bacteria eventually do develop resistance.

Click on the screenshot below to read the original article, or download the pdf here.  The researchers hail mostly from UC Santa Barbara, but also come from UC Davis, Singapore, and Australia.

I found the link from reader Jeannie, who sent me a short piece on calling attention to the results. That linked to the original paper (above), but added this:

The discovery was serendipitous. The U.S. Army had a pressing need to charge cell phones while in the field — essential for soldier survival. Because bacteria are miniature power plants, compounds were designed by Bazan’s group to harness bacterial energy as a “‘microbial”’ battery. Later the idea arose to re-purpose these compounds as potential antibiotics.

“When asked to determine if the chemical compounds could serve as antibiotics, we thought they would be highly toxic to human cells similar to bleach,” said Mahan, the project lead investigator. “Most were toxic — but one was not — and it could kill every bacterial pathogen we tested.”

Such are the totally unexpected side effects of research, and although this was applied research, it’s also a justification for pure research. Remember: the whole apparatus for sequencing DNA, and then the CRISPR technique, gene editing, and so on, began with the simple observation that some bacteria live in hot springs near the boiling point, and some curious scientists who asked “I wonder how they do it.”

Back to the paper. My take will be short as it’s complicated and, to be sure, parts of it are beyond me. The compound they found was COE2-2hexyl, and below is the structure. It can be synthesized without much difficulty using standard methods of organic chemistry, so you don’t have to get it from massive quantities of fungi or other organisms. Captions are from the paper.

Asyou see, it consists of two aromatic central chains with four long carbon tails, each of which has a nitrogen atom in it:

b and c, COE structural modules are depicted by coloured boxes. The intercalation into phospholipid bilayers is driven by the hydrophobic centre and the terminal ionic functionalities, consisting of the conjugated aromatic core (gold module) and hydrocarbon pendants (blue module), which resemble the fatty acid centre of the bilayer. Additionally, the cationic end groups (red module) and terminal acyl chains (pink module) interact via coulombic and hydrophobic interactions with the membrane surface functionalities; specific example: COE2-2hexyl.

It works, as implied in the caption above, by attacking the cell membranes of bacteria, disrupting essential functions of the membrane. These include the ability of the bacterium to absorb and emit cell contents, to help the bacterium metabolize, and also, critically, to divide. Here’s how COE2-2hexyl looks when it gets into the bacterial membrane and disrupts it. Other similar compounds, called COEs, have the same shape and do the same thing:

COEs share a modular structure that spontaneously integrates into the bacterial membrane

This compound was tested on 17 bacterial isolates taken from people with drug-resistant infections:

You’ll recognize some of these as bacteria that cause gonorrhea, tuberculosis, pneumonia, dysentery (Shigella flexneri) Acinetobacter baumannii, which causes bad infections associated with hospitals, and so on. All of these were isolates taken from humans who had shown antibiotic resistance.  The drugs were tested in vitro, using mouse cell cultures that were infected with bacterial isolates from humans, and also in vivo, in mice that had been infected (there were of course controls that had been mock-treated). (I have to add that I feel sorry for the mice in the control group.)

As the authors note (my emphasis):

Expanded antibacterial activity analyses revealed that COE2-2hexyl exhibited broad antibacterial activity against all 17 clinical bacterial isolates tested (Table 1). Notably, methicillin-resistant S. aureus (MRSA, MT3302) and CRE K. pneumoniae (MT3325) were derived from sepsis patients with refractory bacteremia, whereby the CRE organism was resistant to 20/22 antibiotics determined by clinical VITEK testing (bioMerieux, Inc.) and 19/24 antibiotics determined by broth microdilution.

Note that it worked when nearly all antibiotics had failed. The authors also made two derivatives of this compound, adding one cabon atom to two of the four chains; these two compounds also showed antibacterial activity against 9 drug-resistant bacterial isolates tested.

Of course you’re wondering “well, this is great, but is it safe?”  It was, even in higher doses, and in the doses that killed bacteria. But of course it was safe in mice but may not be in humans. Clinical testing will be in order, and that might take a long time before we see if this and its derivatives are truly “wonder drugs”.

Finally, testing the compound for relatively long periods against bacteria showed that the bacteria did NOT develop immunity to the drug (that’s via natural selection, of course), which is really good news, since few antibiotics have not been overcome by mutations that render bacteria immune to them. (I believe that the Streptococcus bacterium that causes “strep throat” has never evolved resistance to penicillin, nor has the polio virus evolved immunity to polio vaccines, but such cases are rare.) Now, as Orgel’s Second Rule states, “evolution is cleverer than you are,” and eventually, if COE2-2hexyl is used for long enough, bacteria might find a way around it. But right now, things look promising.

Finally why are bacteria unable to evolve resistance to COE2-2hexyl? The clue is in this sentence in the paper:

COE2-2hexyl had specific effects on multiple membrane-associated functions that may act together to disrupt bacterial cell viability and the evolution of drug-resistance through a mechanism of action distinct from most membrane disrupting antimicrobials or detergents which destabilize.

The compound, it seems, disrupts many different functions of the bacterial membrane, and while one disruption might be fixed by one or more mutations in the bacteria, something that screws up your system big time, and in multiple ways, may be impossible to repair, as bacterial mutations that overcome one disruption may make it harder to fix the other disruptions. The more ways a drug can screw up a bug, the less likely it is that the bug can evolve resistance. But remember—bacteria are clever.

I’ll end with the authors’ final paragraph about what’s good about this compound and what needs to be done (mostly efficacy and safety testint in humans). But if this thing works out, it will be a medical advance of almost unparalleled value (bolding is mine):

The ease of molecular design and modular nature of COEs offer many advantages over conventional antimicrobials due to their intermediate molecular size, sufficient aqueous solubility to achieve efficacy, and the absence of complex chemical structures/chiral centers, making synthesis simple, scalable and affordable. The COE refinement workflow potentially accelerates lead-compound optimization by more rapid screening of novel compounds for the iterative directed-design process. It also reduces the time and cost of subsequent biophysical characterization, medicinal chemistry and bioassays, ultimately facilitating the discovery of novel compounds with improved pharmacological properties. Additionally, COEs provide an approach to gain new insights into microbial physiology, including membrane structure/function and mechanism of drug action/resistance, while also generating a suite of tools that enable the modulation of bacterial and mammalian membranes for scientific or manufacturing uses. Notably, further COE safety and efficacy studies will need to be conducted on a larger scale to ensure adequate understanding of the clinical benefits and risks to assure clinical efficacy and toxicity before COEs can be added to the therapeutic armamentarium. Despite these limitations, the modular design of COEs enables the construction of a spectrum of compounds with the potential as a new versatile therapy for the emergence and rapid global spread of pathogens that are resistant to all, or nearly all, existing antimicrobial medicines.

h/t: Jeannie

An oath at Columbia University’s “white coat” ceremony for medical students. Is it compelled speech?

February 16, 2023 • 9:15 am

If you think wokeism (or whatever you want to call it) is abating, realize that this kind of add-on to the traditional Hippocratic Oath is proliferating, and these oaths are written by the med students themselves—sometimes with the help of the faculty.  The pledges are recited during the “White Coat Ceremony”—the occasion during which new medical students get their white doctor coats. The ceremony actually has existed only since 1993, and we’ve already seen several that include a student-written oath. (Remember, this is a student-inspired add-on to the traditional Hippocratic Oath (see Greek original and translation here). These days, if students produce add-ons, you know what they’re going to be.

The two I’ve posted about include one at the University of Pittsburgh and the other at the University of Minnesota, with the latter including a land acknowledgment and pledging to honor “all Indigenous ways of healing that have been historically marginalized by Western medicine.” (Some of those ways of healing, of course, are useless and shouldn’t be “honored” in any sense.) FIRE has a list five such med-school ceremonies (see below).

Well, this is a ceremony that cannot help but spread, for students can’t help but inject their ideology (debatable ideologies, as you can see below) into nearly everything. This one took place at Columbia University’s  Irving Medical Center in August of 2021 for students of the class of 2025, and was shown and reported on by the Medical Center itself:

For the first time in the medical school’s 254-year history, the incoming MD students recited their own Class Oath, updating the Hippocratic Oath to better reflect the values they wish to uphold as they enter their medical training. The Class Oath includes a commitment to “acknowledge and embrace the diversity that exists within all communities, and the formative influence that the Washington Heights community will have on my future as a physician.” This year’s ceremony at the Armory was convened in person with limited faculty and guests and was also watched virtually via Zoom.

The idea for a new Oath came up a year ago, shortly before the White Coat Ceremony for the VP&S Class of 2024 but with little time for students to write the content. With this in mind, the rising second-year medical students asked to help members of the VP&S Class of 2025 write their own Class Oath. The writing took place over many weeks this summer. Current MD students were trained by the VP&S Office of Medical Education as writing facilitators to work with the incoming students and collaborating faculty members. Going forward, each incoming MD class will have the opportunity to create its own Oath.

As you see, this ideological oath will continue in perpetuity. Not at all ideological, you say? Well, not entirely, but surely in part. Listen to the recitation and then read the text below.


Here’s the text from another Columbia Medicine website (bolding is not mine, but from the original)

Class of 2025 Oath

“We enter the profession of medicine with appreciation for the opportunity to build on the scientific and humanistic achievements of the past. We also recognize the acts and systems of oppression effected in the name of medicine. We take this oath of service to begin building a future grounded in truth, restoration, and equity to fulfill medicine’s capacity to liberate.

I make this pledge to myself, my classmates and future colleagues, and the individuals and communities I will serve.

I acknowledge that my role is to inform my patients, accompany them in moments of wellness and vulnerability, and respect their privacy and autonomy while empowering them to flourish.

I promise to take care of my future patients by engaging in dialogue, listening to their lived experience, and tailoring my recommendations to their unique circumstances.

I commit to honor the relationship formed between patient and physician by maintaining confidentiality at all times.

I vow to contribute to the field of medicine through ethical study and equitable evidence-based care, and to treat my patients and represent my profession with compassion, humility, and equanimity.

I acknowledge the past and present failures of medicine to abide by its obligation to do no harm and affirm the need to address systemic issues in the institutions I uphold. 

I promise to critically examine the systems and experiences that impact every person’s health and ability to receive care.

I vow to use this knowledge to uplift my patients and disrupt the injustices that harm them as I forge the future of medicine.

I acknowledge the background and experiences that enrich my perspectives while recognizing the limitations, shortcomings, and biases that I bring to each encounter with patients and colleagues. 

I promise to self-reflect diligently, to confront unconscious prejudices, and to develop the skills, knowledge, and character necessary to engender an inclusive, equitable field of medicine.

I commit to fostering empathy and a culture of care, not just for our patients but for ourselves and our colleagues in healthcare.

I vow to remember the humanity and fallibility of myself and every member of the care team, and to call upon my colleagues for assistance in recognition of the limits of my knowledge and skills.

I acknowledge and embrace the diversity that exists within all communities, and the formative influence that the Washington Heights community will have on my future as a physician. 

I promise to respect, regardless of identity or socioeconomic status, the fundamental dignity of all patients, colleagues, and community members, and their right to quality care.

I vow to restore trust where it has been broken and to inspire and nurture trust in the relationships I build with patients, through collaborative effort with my classmates, colleagues, and communities.

Let us bow our heads in recognition of the gravity of this oath; we swear to faithfully engage with these ideals and obligations for the ongoing betterment of medicine and humanity.”

Note that while a lot of it is traditional and appropriate, there are also tropes about confronting unconscious bias (a contentious claim) and pledges to confront “systemic issues,” and to “disrupt injustices”. It’s as much aboout self-flagellation of the students as it is about their promises for the future.  Note as well that the pledge to abide by “evidence-based care” conflicts with Minnesota’s pledge to to honor “all Indigenous ways of healing that have been historically marginalized by Western medicine.” I guess “honoring” is different from “employing”.

I will leave you to comment on this or the issues it raises, but I’ll just add that FIRE (the Foundation for Individual Rights and Expression) has written about its concern with these ceremonies, noting this about the Minnesota oath in particular and these oaths in general:

Similar student-authored oaths were adopted in recent years at medical schools like HarvardColumbiaWashUPitt Med, and the Icahn School of Medicine.

. . .Again, while universities, students, and faculty are free to encourage or promote DEI-type values, forcing others to say they believe in these concepts is not only contrary to many universities’ legal obligations — but violates their moral obligations, too.

Consider: Even students or faculty who broadly agree with a university’s stance on DEI may believe, for example, that land acknowledgements are merely performative. Or a faculty member who studies race and gender may have highly nuanced views on DEI not reflected by the university’s stance. Students, likewise, may disagree with other aspects of a given DEI pledge.

Medical students possibly being made to read verbatim from ideological pledges if they wish to become physicians would be a new low.

Why not law students, engineers, and business-school students, too?

I’m not sure that a lawsuit is in the offing (though FIRE’s article notes it’s looking for students forced to recite one of these oaths, ergo someone with standing to sue), but even so this comes pretty close to compelled speech. So far nobody’s been punished for not mouthing the words (though they may all have to stand up), but surely a substantial proportion of students don’t agree with the pledges they’re forced to recite, and would probably prefer to refrain from doing so. They’re in med school to become doctors, not social engineers.

h/t: Wayne

National Health Service ends “gender-affirming care,” replaces with “holistic and appropriate” care

October 25, 2022 • 9:45 am

The NHS has come to its senses and issued a whole new set of protocols for treating gender dysphoric youth. Previously, the Tavistock Clinic in London was the go-to place for these children, whose numbers have risen rapidly in the past few years, especially for females (graph below from here):

But there were complaints from patients, and a commissioned report on the Clinic by Dr. Hilary Cass damned the form of care practiced at Tavistock: “affirmative care,” which in practice meant affirming a child’s wishes about changing sex, which led to buttressing their wishes by giving puberty blockers to prepubescent youth, and ultimately adding hormone therapy and referring children for surgery to remove breasts and remodel genitals (the NHS never covered gender-transition surgery).

The problem was that many youth with gender dysphoria have mental problems or are simply distressed about their sexuality, and that lots of these difficulties resolve themselves without changing gender—often by becoming gay, which involves no drugs or surgery.

It was this rush to judgment and treatment, combined with a spate of pending lawsuits by former patients, that led to Tavistock’s downfall. Its functions will not only be farmed out to other centers, but the whole notion of “affirmative care” is being abandoned in favor of what I see as more sensible approach, which the article below calls “a holistic view of identity development in children and adolescents. Preliminary assessment will include “nonaffirmative” but supportive therapists, and there will be no “rush to hormones”;  puberty blockers (whose long-term effects are still largely unknown)  and hormones like testosterone administered only in clinical trials. The whole National Health Service protocol has been revised, and those who evade it by, say, ordering their own hormones, will not be further supported by the NHS.

These changes, following protocols already implemented in Sweden and Finland, are described in the article below from the Society for Evidence Based Gender Medicine (click to read):


Here’s what the article says about why the Tavistock protocols were abandoned.

The reasons for the restructuring of gender services for minors in England are 4-fold. They include (1) a significant and sharp rise in referrals; (2) poorly-understood marked changes in the types of patients referred; (3) scarce and inconclusive evidence to support clinical decision-making, and (4) operational failures of the single gender clinic model, as evidenced by long wait times for initial assessment, and overall concern with the clinical approach.

And a bit about the new program:

The new NHS guidance recognizes social transition as a form of psychosocial intervention and not a neutral act, as it may have significant effects on psychological functioning. The NHS strongly discourages social transition in children, and clarifies that social transition in adolescents should only be pursued in order to alleviate or prevent clinically-significant distress or significant impairment in social functioning, and following an explicit informed consent process. . . 

The new NHS guidelines represent a repudiation of the past decade’s approach to management of gender dysphoric minors.  The “gender-affirming” approach, endorsed by WPATH and characterized by the conceptualization of gender-dysphoric minors as “transgender children” has been replaced with a holistic view of identity development in children and adolescents. In addition, there is a new recognition that many gender-dysphoric adolescents suffer from mental illness and neurocognitive difficulties, which make it hard to predict the course of their gender identity development.

“Social transition” comprises the acts of medical professionals facing children with gender with gender dysphoria and helping them change gender with puberty blockers and hormones.

There are ten highlights (i.e., changes from the Tavistock protocols) in the NHS’s new system. They’re described in the article, and I’ll put them below with one or two aspects of each intervention (there are more in the article). All extracts from the article are indented; my own comments are flush left.

1. Eliminates the “gender clinic” model of care and does away with “affirmation”

  • “Affirmation” has been largely eliminated from the language and the approach. What remains is the guidance to ensure that “assessments should be respectful of the experience of the child or young person and be developmentally informed.”

  • Medical transition services will only be available through a centralized specialty Service, established for higher-risk cases. However, not all referred cases to the Service will be accepted, and not all accepted cases will be cleared for medical transition.

2. Classifies social gender transition as an active intervention eligible for informed consent

  • The NHS is strongly discouraging social gender transition in prepubertal children.

They outline the criteria needed to address gender transition, which include “persistent and consistent gender dysphoria” and “a clear and full understanding of the implications of social transition.”

3. Establishes psychotherapy and psychoeducation as the first and primary line of treatment

  • All gender dysphoric youth will first be treated with developmentally-informed psychotherapy and psychoeducation by their local treatment teams.

This is one of the main ways the Tavistock model failed: it didn’t use therapists who would assess the patient objectively rather than push them into changing genders.

4. Sharply curbs medical interventions and confines puberty blockers to research-only settings

  • The NHS guidance states that the risks of puberty blockers are unknown and that they can only be administered in formal research settings. The eligibility for research settings is yet to be articulated.

  • The NHS guidance leaves open that similar limitations will be imposed on cross-sex hormones due to uncertainty surrounding their use, but makes no immediate statements about restriction in cross-sex hormones use outside of formal research protocols.

This is an important change because the long-term effects of puberty blockers, especially used in combination with hormones like estrogen or testosterone, are not known.

5. Establishes new research protocols

  • All children and young people being considered for hormone treatment will be prospectively enrolled into a research study.

  • The goal of the research study to learn more about the effects of hormonal interventions, and to make a major international contribution of the evidence based in this area of medicine.

These studies will be continued into adulthood, as they should be. It’s important to know whether there are delayed injurious effects of hormones, as well as psychological “desisting”, or regret for changing gender.

6. Reinstates the importance of “biological sex”

  • The NHS guidance defines “gender incongruence” as a misalignment between the individual’s experience of their gender identity and their biological sex.

This change and the others implicitly assume that there is such a thing as biological sex and that it’s not a social construct. They don’t say there are only two biological sexes, but I think that’s assumed.

7. Reaffirms the preeminence of the DSM-5 diagnosis of “gender dysphoria” for treatment decisions

  • The NHS guidance differentiates between the ICD-11 diagnosis of “gender incongruence,” which is not necessarily associated with distress, and the DSM-5 diagnosis of “gender dysphoria,” which is characterized by significant distress and/or functional impairments related to “gender incongruence.”

The DSM-5 is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition—the latest set of criteria used to diagnose mental illness. The addition of distress is important because without distress the panoply of treatments outlined for gender dysphoria aren’t used.

This is one of the most important changes, advocating a variety of expertise brought to bear on gender dysphoria, none of it dedicated to affirming the patient’s wishes:

8. Clarifies the meaning of “multidisciplinary teams” as consisting of a wide range of clinicians with relevant expertise, rather than only “gender dysphoria” specialists

  • The NHS guidance clarifies that a true multidisciplinary team is comprised not only of “gender dysphoria specialists,” but also of experts in pediatrics, autism, neurodisability and mental health, to enable holistic support and appropriate care for gender dysphoric youth.

  • Such multidisciplinary teams will be the hallmark of the new Service, into which challenging and risky cases may be referred. In addition to specific expertise in gender identity development and incongruence, the clinical leadership teams of the newly-established Service will include strong, “consultant level” expertise in a wide range of relevant areas:

    • neurodevelopmental disorders such as autistic spectrum conditions

    • mental health disorders including depressive conditions, anxiety and trauma

    • endocrine conditions including disorders of sexual development pharmacology in the context of gender dysphoria

    • risky behaviors such as deliberate self-harm and substance use

    • complex family contexts including adoptions and guardianships

9. Establishes primary outcome measures of “distress” and “social functioning”

  • The rationale for medical interventions for gender-dysphoric minors has been a moving target, ranging from resolution of gender dysphoria to treatment satisfaction.  The NHS has articulated two main outcome measures of treatment: clinically significant distress and social functioning.

These criteria are used for specifying treatment for other illnesses like depression.

10. Asserts that those who choose to bypass the newly-established protocol will not be supported by the NHS

  • Families and youth planning to obtain hormones directly from online or another external non-NHS source will be strongly advised about the risks.

The NHS will not support further treatment of those who obtain and take hormones outside of the NHS’s protocols.

Can anybody argue that these are not more sensible protocols than the ones used previously? Since most gender dysphoric children turn out to be either cis or gay if not given hormones and surgery, shouldn’t one take these kinds of precautions before injecting or cutting such people?

The premise, of course, is that many children who are dysphoric don’t need “affirmation” (especially if there’s social pressure to change their gender), but compassionate therapy to see how serious their problem is and how strongly they wish to change identity. If you can’t vote until you’re 18, why should you be able to start changing your hormones and body parts before then?  18 is just a subjective age, of course, but the protocol is based on not immediately accepting the views of children—or their parents, who can pressure kids destined to be gay into seeing themselves as transsexuals—that they’re in the wrong body. You don’t just affirm that right off the bat, but ascertain it with intensive therapy.

Of course there will be many objections to these protocols by trans activists who are of the “affirmative care” stripe, but I think that in twenty years we’ll look back on the present as a time when many children were harmed by improper medical and psychological care. That’s the basis of the more than 1,000 lawsuits likely to be filed against Tavistock.