Category: medicine

Two examples of wokeness: cancer care and moccasins

September 3, 2023 • 9:30 am

CANCER CARE

This first link below was sent by my partner in crime Luana, and is from John Lucas’s Substack site “Bravo Blue”. (Lucas was any Army ranger who became an attorney.)

Lucas is decrying the “woke propaganda” to which he was exposed when he checked into the hospital for cancer care. Click below to read, and subscribe if you read often:

An excerpt:

I recently experienced my own personal encounter with this propaganda when filling out a pre-surgery questionnaire at my hospital. This is the story.

I am a cancer patient. Since last January I have been diagnosed with two types of cancer that have necessitated three surgeries so far. For my most recent surgery, I was referred to an oncological surgeon at the VCU Medical Center, which is associated with Virginia Commonwealth University.

At this point, I must add a personal advisory note: The VCU Medical Center enjoys a superb national reputation. Other members of my family have been treated there and have received superb care. Nothing I say here is intended to disparage any of the individual care-givers at the hospital in any way. All, from my surgeon to the kind lady who escorted me to my car after my overnight stay, were uniformly kind and professional. Any criticism I may have is directed at the government-sponsored infection of the medical system with the WOKE virus, not at any individual physician or other medical or support staff.

The forms:

When I checked in at the hospital for my pre-surgery consultation, because I was a new patient for them, they gave me the usual medical history form to complete. After completing it, I turned to a second two-page form. I printed my name at the top and, rather unthinkingly, began to fill it out. I was in a bit of a hurry to complete it before I was called back to see my surgeon, so at first I did not pay a great deal of attention to it. So, I dutifully answered the first question, which asked, “What is your “Sexual Orientation?” That should, however, have been an immediate red flag, causing me to wonder, “What on earth does this have to do with cancer surgery?” But out of habit and without thinking, I checked the block for “Straight (Not lesbian or gay).” Had I read it closer and given it a moment’s thought, I would have been nonplussed by the other answers on the menu: “Lesbian,” “Gay,” “Bisexual,” “Something else,” or “Don’t know.”

The first page:

The next question roused me out of my inattentiveness: “How do you describe your gender?” It then gave a menu of six possible answers: “Male,” “Female,” “Transgender male,” “Transgender female,” “Other” and – again – “Unknown.” Like the other questions it also included an option “not to disclose.” My surgeon’s notes from our consult include the notation that I was a “79 year old male.” In view of that rather obvious observation, how or why I was given an option to refuse to disclose my gender is unclear.

At that point I knew something was very wrong.

For me, the final straw was the third question: “What was your sex assigned at birth?” The options were “Male,” “Female,” “Unknown” (again), or “X.  I was left to guess what “X” is; it was not defined.

The woke questions, avers Lucas, are irrelevant to cancer care, though they could have been relevant if, say, he was there for treatment in urology or gynecology. “Sex assigned at birth”, of course, is a phrase that really angers me, because it’s not accurate. Even if doctors use secondary sexual characteristics like genitalia to diagnose sex, sex is not “assigned at birth”, as if it were something arbitrary that doctors decide. It is observed at birth, even if what you really want to observe is whether a newborn has the biological equipment that evolved to make either small and mobile or large and immobile gametes. But genitalia show an almost perfect correlation with biological sex, so they’re a useful surrogate way to determine it.

But “sex assigned at birth” is becoming more frequent despite its inaccuracy. Why? Because it plays right into gender activism. One’s gender is, of course, often self-assigned, though the vast majority of people bear a social role of gender that corresponds to their biological sex.  But you don’t have to distort the biological definition of sex to placate gender activists. And it also misleads people about science. The gender activists answer: “Forget the science; we’re making sex conform to gender.”

But I digress; here’s page 1 of the form:

But wait! There’s more!

The questions continued on a second page with more inanities.

It asked, for example, what pronouns I use, and – again – the option to say that I what pronouns I use is “unknown.” It occurred to me that a person who is unaware of what pronouns they use may belong in a hospital ward other than the cancer ward. A separate question inquired whether I “presently have” breasts, a vagina, a penis and “prostate/testes,” (They apparently think a man cannot have one without the other.) with instructions to check off all that you have. The most unintentionally hilarious part of the form was the instruction to “write in the space beside the organs listed if there is another word you would like your healthcare provider to use to refer to that body part.” Had I been thinking more clearly at the time, I could have had a lot of fun with that one.

I answered all the questions after the first one by only a single printed “I am a man.” Enough said.

Lucas found that these forms are widespread, and are apparently pushed by the government: the Centers for Disease Control:

Later when I had returned home to complete my recovery, I began to investigate the origins of this form. I quickly found that a very large number of hospitals and medical schools use this or a similar form. For example, the University of Utah health care system has a similar set of questions that it says it will ask each patient every six months.

After all, you may be genderfluid and your pronouns could change.

I discovered that this agenda is being pushed by the federal government. The CDC’s web site lists the questions that medical providers should ask. Its recommended questions are substantially the same as those on the VCU Medical’s questionnaire. However, there are some differences. In addition to the options provided by VCU Medical for “Gender identity,” the CDC recommends an option to specify “Genderqueer/gender nonconforming neither exclusively male nor female.” For “Sexual orientation” it adds, “Queer, pansexual, and/or questioning.” The CDC also suggests other possible pronouns such as “Ze,” “Zim,” and “Zirs.”

But they left out “leaf”!

**************************

MOCCASIN ACKNOWLEDGMENTS

Reader Gregory called my attention to this Eddie Bauer ad:

Here’s another view. These look just like the work boots that were de rigueur when I was in college, along with Army fatigue jackets and jeans. (It was the proletarian look.)

Although to me this looks like a conventional work boot, Eddie Bauer claims that it incorporates features of the moccasin, a form of Native American footwear.  I swear I can’t see any resemblance (see below to compare) but Eddie Bauer apparently feels it has to acknowledge it to show its commitment to social justice.

The blue link in the box goes to this site, where Eddie Bauer promises to investigate which products have features that have been appropriated from indigenous peoples.

Here, however, are three pair of genuine Native American moccasins shown on Wikipedia. (They were often beaded.) They bear NO resemblance to the Eddie Bauer “Moc Toe boots,” even in the toes:

Osage:

Kiowa:

Cheyenne:

But why stop at Native Americans? I’m sure there are many products with features adopted from cultures throughout the world.  Below is an Eddie Bauer woman’s dress that is clearly culturally appropriated from the culture of Rajasthan in India, known for its block prints very similar to the ones on this dress. This is blatant and unacknowledged appropriation from people of color:.

To be fair, the Eddie Bauer site also notes they’re starting a partnership with a Native American collective, which is great, but do they have to flaunt this? Of course they do, or they’ll get slammed on social media: the kiss of death for a company.

That said, at least the partnership accomplishes something.

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.

 

Conclusion

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.

UPDATE:

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 “read more”)]

Continue reading “Guest Post: What a student pharmacist thinks about puberty blockers” →

Another merging of scientific with indigenous medicine, once again lacking specificity

August 15, 2023 • 11:30 am

Much as I’d like to believe otherwise, I see this as a “virtue-signaling” collaboration on the part of Roche, which aims to meld not just Māori medicinal practices with modern medicine, but also Māori “values”. I’m not sure what kind of “values” differ between Māori and so-called “Western” medicine because both presumably value “getting well” and “not getting sick” as the goals of healcare.

Click below to read the article from the New Zealand Herald:

Excerpts (I’m on a ship, and since the newspaper was too lazy to translate the Māori words into English, I don’t feel obliged to, either):

Te Rūnanga o Ngāti Whātua and global pharmaceutical company Roche Pharmaceuticals have recently set up Tū Kotahi, a new partnership that will see modern medicine meeting traditional Māori values and practices.

The pact calls for investigating novel approaches to disease prevention, treatment, and wellness for descendants of the iwi, hopefully bringing it to other iwi in the future.

The iwi’s co-chair, Dame Naida Glavish, says the “open, honest and frank” pact opens a new chapter in medical innovation and cultural preservation.

“I feel really good about it because Te Rūnanga o Ngāti Whātua will stand in its own mana motuhake and so will Roche. There is a need, of course, to have an understanding between the two in terms of mana motuhake, total sovereignty, coming together with each other.”

There’s been mutual respect from the iwi for Roche understanding the body and physical health, while Roche admires mātauranga Māori in relation to the wellness of hinengaro and wairua, she says.

. . .“[Ngāti Whātua] holds a responsibility, every tribe in this country agrees, to manaaki all manuhiri who are in our tribal rohe. It benefits all in Ngāti Whātua and, in the rohe of Ngāti Whātua, others will benefit.

“We have no problems whatsoever that if Roche can work with Ngāti Whātua, Roche can work with Te Kahu o Taonui [Tai Tokerau tribe collective]. If they can with us, they can with anyone.”

Putting patients first, according to Roche Pharmaceuticals’ new NZ general manager Alex Muelhaupt, involves acknowledging the health disparities experienced by indigenous peoples.

I see no evidence of what kind of merging of the two “health systems” will take place. Instead, it looks as if the responsibility is on Roche to eliminate “health disparities experienced by indigenous peoples.  If there are such disparities, and they’re due to bigotry and not cultural differences, then yes, they must be addressed. But that involves social interventions, not medical ones.

And of course the Māori may have medicinal plants that modern medicine has neglected, and if so, they should be investigated: using the double-blind trials that are the gold standard of testing remedies. 

But Māori “healing” also includes chanting and singing: will Roche also test those practices? And how? Will they do nonsensical chants and songs as a control?

The absence of examples, and the finishing of the piece by an implicit claim that health disparities are caused by bigotry, is what makes me suspicious about this endeavor. If they’d give just ONE example of a possible testing of Māori practices with the aim of incorporating them into modern medicine, I’d feel better. But of course we never see that in these endeavors, and I’m pretty sure why.

Since only 4% of all Kiwis can hold a conversation in Māori, while only 55% of Māori adults can speak some of the language, while only 17% of Kiwis are Māori, I would think that New Zealand’s most widely-read newspaper could to its readers the benefit of translating indigenous words in articles such as the above.  I can’t think of a good reason why not. If they want to effect cultural fusion by teaching Māori words to the non-Māori-speaking populace, which I see as a good form of cultural appropriation, they need to do some translating. That they don’t I see as a form of arrogance, or truckling to the indigenous population

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 Lancet’s editor jumps the shark, disses global health because of its racist and white supremacist history

May 25, 2023 • 9:30 am

I don’t know much about Richard Horton, the editor of The Lancet (one of the world’s top medical journals); but what is clear is that he’s uber-woke. He was, for example, responsible for this controversial cover:

 

There have been other political covers, other woke editorials by Horton, and a fair few woke articles that, in saner times, wouldn’t be published in The Lancet. But once someone like Horton is handed his bully pulpit (and is presumably supported by “allies”), he can go hog wild with proselytizing and virtue flaunting. Yes, he may mean well, but his latest op-ed is so over the top, so full of the drive to reform everything in the world, and so unhinged in its tone, that there was a reason I once called The Lancet “the medical Scientific American.”

Here’s my own brief summary of Horton’s op-ed that you can (and should) read by clicking the screenshot below. These are my words:

“Global health” is a manifestation of colonialism and white supremacy, an exclusive and structurally racist club that must be decolonized and dismantled. We shouldn’t waste our time pursuing the traditional version of this practice, which won’t be decolonized until the entire world is fixed: rid of war, racism, unequal wealth, climate skepticism, and all other manifestations of right-wing politics.”

But what is “global health”? Well, I use the Lancet’s own definition:

. . . . we offer the following definition: global health is an area for study, research, and practice that places a priority on improving health and achieving equity in health for all people worldwide. Global health emphasises transnational health issues, determinants, and solutions; involves many disciplines within and beyond the health sciences and promotes interdisciplinary collaboration; and is a synthesis of population-based prevention with individual-level clinical care.

This, then, involves not just improving health of people throughout the world, but achieving “equity in health,” which to me means that everyone gets equal opportunities to access health care. Well, that seems fine: equal opportunity for everyone is what I want. Note, however, that they emphasize “equity in health,” not simple “equity,” which means representation of  all underserved groups of people in professions—presumably healthcare here—in proportion to the groups’ occurrence in the population.  But, as you see below, “equity in health” has been reinterpreted by Horton, half intoxicated with wokeness, into simple equity in everything, which leads him to not only indict “global health” for racism and colonialism, but also to call for sweeping reforms of the entire planet.  Yes, most of these reforms would be nice, but right now there are sick people to cure, and we can’t wait centuries until everyone has more comparable incomes before we start making people well.

Click to read:

Seriously, Horton has gone the Scientific American route.  I don’t mind him noting the underlying cause of health disparities, but here he picks up a megaphone, mounts a soapbox, and shouts his own views to the world. I will quote him so that you’ll see that I’m not making this up. I’ve put the more interesting claims in bold:

Global health has become fashionably unfashionable. The case against global health is strong. Global health is the invention of a largely white and wealthy elite residing in high-income, English-language speaking countries. The discipline claims to be concerned about the health of people living in low-income and middle-income settings. But the resources—human, infrastructural, and financial—underpinning global health are mostly concentrated in those countries already replete with power and money. “Helicopter” research is not uncommon. The contribution of scientists and research funders to sustainable advances in health care in the countries of their alleged concern is minimal. More often, the relationship between western medical science and the countries they work in is extractive. Global health institutions are mostly led by western-educated men. Global health agencies are only superficially member-state organisations. In truth, influence lies with those nations providing the greatest resources. Global health has enabled public health schools and university departments to continue to enrich themselves through exorbitant student fees and generous research grants. Global health journals are no better. Most are creatures of western medical publishing houses, even those that proclaim radical open access histories. The unearned privileges of a few suppress the justified demands of the many. It is hard to avoid the conclusion that global health is little more than an exclusive club, disguising its colonial origins and practices in the stirring language of equity and justice.

That’s a big passel of accusations. (He doesn’t note that modern science is also largely the invention of a “white and wealthy elite”.)  First , I take issue with his claim that the desire to give everyone equal access to health care is the product of a “white and wealthy elite”, whose faux concern for sick people throughout the world really masks a desire to enrich themselves and their “colonialist” countries. Could it be that the powerful and rich countries like Britain and the U.S. (once colonialist, but no longer) simply had the resources and the moral wherewithal to do something about global health?

By the way, I happen to know a few people in global health, and I detect no whiff of colonialism about them, but rather a dogged determination to give medical care to people in poor countries. And believe me, they have not gotten rich doing so. Those are, of course, anecdotes, but Horton gives no data at all.

But you can see where he’s going.  He wants global health “decolonized,” which presumably means that the initiatives of rich, white, colonialist countries would give way to those of poorer countries. But right now that’s not possible—at least not without the help and funding from wealtheir nations.  I also note that to do so we must solve “inequities,” and by that he doesn’t mean just healthcare inequities, but even inequities in everything, including journal fees, which have already been tackled.

The view that global health is a colonial project underlies the call for decolonisation. As Franziska Hommes and colleagues wrote in The Lancet Global Health in 2021, the goal of decolonisation must be “to critically reflect on [global health’s] history, identify hierarchies and culturally Eurocentric conceptions, and overcome the global inequities that such structures perpetuate”. The democratic promise of global health to be an inclusive enterprise has been broken. Some critics argue that global health can never solve inequity. Some go further and suggest that global health is structurally racist. It is hard to disagree with these conclusions. Although global health journals might mean well, the operation of waiver policies for article processing charges has created a culture of humiliation for scientists who cannot afford western journal open access fees. Journals have worsened Northern ventriloquism, where scientists from lower-income settings feel forced to adhere to high-income norms and standards to be permitted to publish in their pages. In Global Health in Practice, Olusoji Adeyi offers a compelling analysis of how imperialism and colonialism became the “founding pillars” of global health. And his observation that “The din of protest against colonialism in global health is getting louder and it has merit” should provoke those of us who work in global health to pause. For Adeyi is surely right that “the Global North decides the narrative and assumes the omniscience to tell the Global South what the latter needs, when it can have it, how to do it, and on whose terms it must be done”.

But science journals, as Horton admits, have already waived publication fees for scientists and doctors from poor countries. Yet even in that gesture Horton finds sin, as fee waivers have created a “cultural of humiliation.” Okay, Dr. Horton, what’s the alternative? If there are to be publication fees, should we eliminate the “humiliation” by hitting authors from poor countries with those huge (and, to my mind, exorbitant) charges? Only a Pecksniff would find in an attempt to achieve equity yet another form of inequity!

And what are the “high-income norms and standards” to which those from poorer countries need not adhere for publication? Does he mean that we should give up standards of merit when refereeing papers from that group? Apparently! Let us lower the bar for papers coming from scientists in underserved countries. Perhaps we shouldn’t require them to have control groups, or use statistics instead of “lived experience”?

Well, I might as well cite the the rest of Horton’s short article. At the end the editor seems to lose it, calling for impossible (though desirable) reforms that must replace the effort we put into global health care. What he means is that we must get rid of right-wingers—the true opponents of global health:

When I was a medical student, I remember those attached to various causes arguing with passion among and against ourselves, viewing one part of our group as betraying the real truth that we were seeking to defend. Those on the progressive wing of politics are supremely good at introspective annihilation. And that same process of internal obliteration is now unfolding in global health. While we identify enemies among ourselves, we miss the larger story of just who our opponents really are—those trying to destroy the conditions for achieving the right to health, equity, liberty, and social justice. For the real enemies of the values we stand for do not sit within the ranks of global health. They are to be found in governments that instinctively mistrust—and who wish to undermine and defund—global organisations. They will be found among those who demonise refugees. They are the climate sceptics, anti-vaxxers, and purveyors of scientific misinformation. They are those who attack the redistribution of wealth, those who believe that war brings peace, and those who defend racism under the guise of patriotism. Global health practitioners should certainly engage in robust discussions about the meaning of their discipline. But they should be clear about who our struggle is really against. It is not global health. Instead, we must work harder together to create a new political frontier and forge a new collective against the true enemies of health.

This has very little to do with making people in poor countries better, for it is a political and ideological program to which he’s calling The Lancet’s readers.  (Note the language of war: “enemies”.) High-sounding words indeed, and some of them I agree with (who could help but criticize anti-vaxxers and climate skeptics?). But demonisizing refugees? That is a viable discussion in the U.S. right now, and those who call for limits in immigration can hardly all be tarred with “demonising refugees.” This is hyperbolic, divisive, and inaccurate language. In the end, Horton calls us to follow his own program, for apparently he alone has identified the “true enemies of health.”

Even on her worst days Sci. Am. editor Laura Helmuth has never written stuff like this, even if she believes it. But Horton is turning The Lancet from a medical journal into Mother Jones. I wonder how many doctors adhere to his hyperbole and to his political program. Does he represent the views of British medicine? And what gives the editor of a medical journal the right to spout his personal politics as if it were official doctrine? Yes, if there are root causes of global health inequality that can be pinpointed, he has a right to mention them. But note that he gives no evidence for his claims, and in the end calls for all readers to join him in forming The New Collective.

Curiously, in an earlier editorial opposing Brexit, Horton, citing John Gray, asserts that the idea of progress itself is a “dangerous fallacy”:

Scientists and those educated scientifically are prone to a dangerous fallacy—we believe in progress. The notion that human beings are forever moving forwards towards a better place. It is a noble vision: the accumulation of knowledge, self-correction, the application of science to enhance society’s wellbeing and wealth. The discipline of medical history is almost entirely based on this admiringly Whiggish precept. But it is mistaken, philosophically and historically. John Gray shattered the notion of progress two decades ago in his bitter polemic, Straw Dogs.

No he didn’t. Only a fool could say that progress hasn’t been possible, and medicine is one of the areas where it’s been profound. Since 1900 the average global life expectancy has more than doubled. You’d have to be a fool to say that that is not progress. (I could go on about medical progress, but there’s no point; you all know about it.)

So, in the paragraph above, Horton apparently rejects an overweening characteristic of liberalism and Englightenment values: belief that progress can be made. Yet what is he doing in this entire editorial but laying out a path for progress and “health equity”?  Either he is confused or has rejected what he wrote in 2019.

It is Horton’s dead certainty that he alone is right, combined with the accusations that his opponents are rich white  colonialist supremacists who promote “global health” not to help others, but to enrich themselves—that combination is the sign of wokeness.  He is sure his critics are wrong, and he will brook no discussion.

As usual, I don’t like publicly calling for people’s jobs, for that’s a woke tactic. But I do think that those who publish The Lancet should take a hard look at what Horton is doing to the journal.  “Bodies with vaginas” indeed!

Let me finish by saying that Horton and I probably agree on many political issues. But that doesn’t mean that were I to become editor of a science journal, I would splash my views all over its pages.

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.

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.

An article in Science takes implicit bias (and its measurement) for granted despite the problems, and suggests interventions that haven’t been shown to work

March 25, 2023 • 11:30 am

Nearly all psychologists have lost their enthusiasm for the idea of implicit bias because of its manifold problems; and the most common test for implicit bias, the IAT (implicit association test) has largely been abandoned by its users. In light of this you’d think the idea and its IAT metric would have dropped out of sight in academics. But that’s not the way it works these days. If an idea like implicit bias fits into the academic Zeitgeist, and we can actually (pretend to) measure how biased people are when they don’t even know it, then it’s full steam ahead with the idea. Ferret out everybody’s bias, because we all have it! And ignore those niggling doubts about the IAT!

This, along with the often problematic notion of “systemic racism”, which persists in all of academia, are two examples of how the authoritarian Left will cling to a concept when it’s been found empirically useless, simply because the idea comports with their ideology.  And this article in Science—one of the world’s two most prestigious science journals—buys straight into the idea of implicit bias and IAT, hardly mentioning that they’re deeply controversial and have not been found to improve race relations. The article also assumes that inequities are due to racism (another dubious conclusion), and that the racism within science is a structural racism, not maniftested by biased individuals but baked into the system. Finally, the article raises the possibility of Big Brother-like monitoring of people to catch the implicit bias that we all know they harbor. (We discussed this suggestion the other day.)

There is no science journal I know of that has not gone in this direction if it’s weighed in at all on that ideology. Science is one and Nature is another.  It’s embarrassing how the two most prestigious journals concerned with understanding nature play so fast and loose with the facts.

Click to read:

The article’s largely about bias in medicine. I’ll give a few quotes showing how embedded the idea of implicit bias is in the article, how little the author and the IAT-users recognize the weaknesses, and describe new methods of measuring implicit bias in light of the IAT’s failure (which they don’t admit). The article is long, but is so similar to others of its ilk that I’ll be brief.

Note the immediate buy-in of the concept of implicit bias below. The article begins with the story of Chastine, a patient with autoimmune disease whose steroids made her gain weight, and then, she claims, doctors would assume that her extra weight was her primary medical condition. (This could, of course, be dispelled by the patient simply telling the doctor this at the outset).:

Stories like Chastine’s are unfortunately common, say researchers who examine how implicit biases—unconscious assumptions based on skin color, gender, sexual preference, or appearance—in health care providers affect patient care. Chastine, who is Black and queer, is now channeling her troubled experience with the medical establishment to aid studies of implicit bias and identify ways to counter it. She is part of a 5-year collaboration between various departments at both the University of Washington (UW) and the University of California, San Diego (UCSD), in which a team is developing a tool to give physicians feedback in real time during patient visits—or shortly after—on what they can do to mitigate their unconscious prejudices.

Here comes the IAW as used by Janice Sabin, a researcher at the University of Washington:

Sabin used the well-known Implicit Association Test (IAT), which determines how strongly an individual associates a trait—such as race or sexual orientation—with a subjective value, such as “good” or “bad.” The quicker you match each concept to a subjective value, the greater the association and the higher your score, which broadly indicates a stronger implicit association between the trait and value.

Sabin found the doctors she tested—a few of them nonwhite—held the unconscious bias that white patients took their medication as prescribed more so than Black patients. It was one of the first studies showing health care providers had unintentional racial prejudices. “It was kind of scary because this was a concept completely foreign to [many] people at the time,” Sabin says.

As I said, the article does mention issues with the IAT, but doesn’t state that its problems (lack of replication, evidence against the unconscious nature of the bias, and the failure of the tests results to lead to effective antiracist programs) are so severe that serious psychologists have abandoned the test:

The IAT remains a standard tool for measuring implicit bias, although some have criticized it because it has to be taken several times to reveal a reliable result, as people’s scores could change every time they take it. Even when people come out neutral on race, most studies will reveal some kind of unconscious prejudice, such as an unrecognized preference of certain sexual orientations or religions.

. . . Scientists have long studied several kinds of interventions that attempt to “erase” implicit bias, but few of them have shown lasting effects. “There is a robust science around implicit bias,” Hardeman says. But, “There is no gold standard for how to intervene right now. It’s imprinted in our brains in ways that make it really hard.”

Simple interventions can dampen biases, as measured by successive IATs, but the changes are usually modest and don’t persist.

. . .Simply asking health care providers to take the IAT without providing context or tools can be counterproductive. A study in 2015 indicated that when medical students are told about their unconscious bias without direction on overcoming it, they tend to get anxious, confused, and nervous interacting with patients who belong to social groups different from their own. That’s why even a quick training on skills to mitigate implicit bias can go a long way, according to Hardeman.

But as the article says (and other articles agree) why measure bias in a way that’s counterproductive if there is no “gold standard about how to intervene” to mitigate bias? Is this all just performative action with no effect on what it hopes to change? And so researchers move on to the Big Brother tests:

That made him [Brian Wood, an infectious disease specialist] eager to take part in UnBIASED’s first experiments, which rely on cameras installed in exam rooms. The cameras in Wood’s Seattle clinic captured interactions between him and his patients, including close-ups of his and their facial features and body language. “I found quite quickly that the patient and I both forgot the cameras were there and just fell into our usual routine and conversation,” he says.

The UnBIASED team then used a type of artificial intelligence (AI) known as machine learning to analyze patterns in the recordings and identify nonverbal cues that could indicate implicit bias. In one of the clips Wood was later shown, he was talking with a patient while leaning forward with his arms crossed on the desk, body language he worries may have made him seem closed and unapproachable. “I reflected on my own as to how that body language might be felt and perceived by the patient,” he says. Wood, who hopes to improve his demeanor, says he welcomed such feedback and is eager for more.

“Reflecting on possible negative moments during a visit was not easy, but felt important and valuable,” Wood says.

The team is now working on translating the experiment’s results into feedback like “digital nudges”—such as an icon that pops onto the computer screen, a wearable device, or other mechanism telling physicians to interrupt patients less or look them in the eye more often. But the UnBIASED team still has challenges interpreting the data in the recordings. For instance, nonverbal signals are nuanced, Hartzler says. “It’s not always as simple as ‘more interruptions means bad.’”

Translation: this method doesn’t seem to work. But nevertheless, the article persists, describing other methods of measuring hidden bias, including clinical simulations of biases and “microaggressions”, constructing training exercises for physicians and nurses, and calling out people on the spot. The problem is that while the article describes a panoply of methods, with at least one “increasing their recognition of bias” in a way that lasted a year (but their own biases or other people’s?), none of the methods seem to have an effect on mitigating bias, conscious or unconscious.  Despite the failure of developing an efficacious program so far, they will persist—forever:

Getting buy-in from whole health care systems could accelerate the process. Recently, California, Michigan, Maryland, Minnesota, and Washington state passed legislation mandating implicit bias training for the medical professionals they license. And since June 2022, Massachusetts physicians are required to take implicit bias training to get a new license or get recertified to practice.

Although researchers see this as a good step, they worry mandated training will become a one-off box-checking exercise. Sustained implicit bias training for physicians should instead be the norm, some emphasize. Hospitals also need to monitor and collect data on health care outcomes for different groups in order to monitor equity, Sabin says. “You have to know where the disparities lie and then begin to work backwards from that.”

It won’t be easy, Hardeman says, noting that, at least in the United States, centuries of white supremacy and other forms of bigotry have resulted in deep-rooted stereotypes and other implicit biases. “Every single person should be thinking about doing this work,” she says. “But if they’re doing it within a system that hasn’t addressed its own biases and racism, then it’s not going to be fully effective.”

Clearly, we’re going to have mandated training for the rest of our lives (much of it involving a form of compelled speech), and all of us who aren’t people of color will be told that we harbor implicit biases and participate in white supremacy, which is now structurally built into medicine.

And yes, of course some people are biased! I can’t help but assume that these people really do mean well instead of just trying to enact an ideology that they know won’t help the situation. But perhaps they should be using methods that work, and if they can’t show they work, they shouldn’t be part of mandated training. It’s not going to make people more “inclusive” to tell them all that they’re ridden with biases they don’t even know about the invisible Klan robes we all wear.

When this kind of palaver invades all of the prestige science journals—in article after article that all say exactly the same thing—you know that we’re in for a long haul.

If you want to measure your own implicit bias for race using Harvard’s IAT, try it here.

h/t: Steve

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 kottke.org 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