Category: medicine and health

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

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

February 16, 2023 • 9:15 am

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

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

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

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

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

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

 

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

Class of 2025 Oath

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

h/t: Wayne

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

October 25, 2022 • 9:45 am

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

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

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

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

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

 

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

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

And a bit about the new program:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

5. Establishes new research protocols

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

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

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

6. Reinstates the importance of “biological sex”

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

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

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

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

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

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

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

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

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

    • neurodevelopmental disorders such as autistic spectrum conditions

    • mental health disorders including depressive conditions, anxiety and trauma

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

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

    • complex family contexts including adoptions and guardianships

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

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

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

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

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

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

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

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

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

Minnesota medical students take ideological oath including, among other things, to “honor all indigenous ways of healing”

October 14, 2022 • 9:30 am

In the last several decades, the “white coat ceremony” has become a tradition at medical schools, with the entering students receiving their doctor’s coats and then reciting the Hippocratic Oath. There are many variants of this ancient oath, and often students write their own version to supplement the traditional one.  As you can imagine, some of these go beyond the doctor’s pledge, adding pledges of social justice, ideological belief, and so on. I’ve seen several versions of these white coat oaths; the FIRE article below mentions them at Harvard, Columbia, WashU, Pitt Med, and the Icahn School of Medicine. But perhaps the one most distressing to scientists and advocates of science-based medicine is this one, recited at the University of Minnesota’s white coat ceremony on August 19.

According to the Foundation for Individual Rights and Expression (FIRE), the speaker is Robert Englander, Associate Dean for Undergraduate Education for the Medical School, who leads the students in what is both a pledge and a prayer. (Curiously, Englander’s university bio has disappeared from its website.)

Now this oath wasn’t written by the administration itself, but, according to FIRE and the agenda of the ceremony, by a committee of fifteen incoming medical students on the “Oath Writing Committee.”  These students may, of course, not represent the beliefs of their class as a whole; in fact, it’s likely that, as usual, it’s the activists who seek the loudest megaphone. Click on screenshot below to see the article, and I’ve put the video of the recitation below that.

Here’s the two-minute video of the oath:

Here’s the oath’s text reproduced from FIRE’s letter sent yesterday to the medical school deam (I’ve bolded the sentence that bothers me the most.)

With gratitude, we, the students of the University of Minnesota Twin Cities Medical School Class of 2026, stand here today among our friends, families, peer, mentors, and communities who have supported us in reaching this milestone. Our institution is located on Dakota land. Today, many Indigenous people from throughout the state, including Dakota and Ojibwe (ooj-jib-way), call the Twin Cities home; we also recognize this acknowledgment is not enough.

We commit to uprooting the legacy and perpetuation of structural violence deeply embedded within the healthcare system. We recognize inequities built by past and present traumas rooted in white supremacy, colonialism, the gender binary, ableism, and all forms of oppression. As we enter this profession with opportunity for growth, we commit to promoting a culture of anti-racism, listening, and amplifying voices for positive change. We pledge to honor all Indigenous ways of healing that have been historically marginalized by Western medicine. Knowing that health is intimately connected to our environment, we commit to healing our planet and communities.

 We vow to embrace our role as community members and strive to embody cultural humility. We promise to continue restoring trust in the medical system and fulfilling our responsibilities as educators and advocates. We commit to collaborating with social, political, and additional systems to advance health equity. We will learn from the scientific innovations made before us and pledge to advance and share this knowledge with peers and neighbors. We recognize the importance of being in community with and advocating for those we serve.

There are the usual arguable claims, which should not be professed or vowed by the students or foisted on them by the dean and fifteen vocal students. The claims include these:

  1. The implication that the original owners of the school’s land was the Dakota people. (Note that the oath says that acknowledgement is “not enough,” but what else will they do for the Dakota people? Will they give the land back, or compensate the original owners? There is no vow to do either.)
  2. Inequities in medicine are not just rooted in past forms of oppression, but are ongoing, and reflect white supremacy as well as other forms of bigotry.
  3. There is “structural violence deeply embedded in the healthcare system”.  What, exactly, do they mean by “structural violence”?
  4. There is a “gender binary” that causes further traumas. I think they’re referring to the “sex binary”, which is real. Few people assert that there is a “gender” binary when “gender” is construed as a person’s sociosexual role.
  5. The students will “honor all Indigenous ways of healing that have been historically marginalized by Western medicine.”  ALL OF THEM?  There are a million of them if you count all forms of indigenous healing overtaken by Western medicine. Yes, a few of these treatments may be efficacious, but almost none have been subject to scientific testing using the gold standard of double-blind treatment.  “Honoring” a form of pre-scientific healing simply because it’s was practiced by indigenous people is ludicrous. Certainly you shouldn’t disparage the people themselves who use such healing, as the treatments were developed outside of science, but you shouldn’t honor all the ways of healing themselves. Most of them don’t accomplish anything; what kind of “honor” does that deserve?
  6. The rest of the oath is boilerplate social-justice jargon, and there’s nothing wrong with that, but this is an ideological/political pledge, not a medical-school pledge. As FIRE notes in its article, this is a form of compelled speech that many of the students might not agree with, but are nevertheless force to give fealty to.

Now many of you can say—and this is likely true—that the social-justice aspects of this pledge are meaningless, and the students don’t have to live up to them.  Nor do the students have to consider shamanism, chanting, herbs, and so on as worthy of “honor.”  (These, by the way, were not historically “marginalized” by Western medicine, but were replaced by scientifically-based treatments because those treatments work.)

If, as the students also pledged, they will “restore trust in the medical system,” they can begin by refusing to honor traditional treatments that don’t work. It is no dishonor to indigenous people to reject methods they developed in the absence of science. I suspect it is the “progressiveness” of this oath that has led to widespread ridicule against it and perhaps to the disappearance of Robert Englander’s bio.

Now on to FIRE, which has legal objections to this oath. Their main objection is that this is not only compelled speech—making students swear to something that they disagree with and is not a requirement of the profession—but also that, in the future, students could be punished for failing to adhere to what they’ve sworn. This is not a fanciful scenario:

From the FIRE article:

FIRE respects students’ rights to express their views. But because only a small committee of all new students penned the statement, some of the other several-hundred students may have been compelled to express that handful of classmates’ opinions as their own. (It’s unclear whether any students dissented and, if so, whether they could opt out.)

We’re also concerned that these subjectively squishy commitments could become de facto professionalism requirements, and that students could be punished for failing to uphold them. For example, what must a medical student do to adequately practice “anti-racism”? And whatever that may be, if she does not (as UMMS understands that term), could she be dismissed for violating her oath? What if she refuses to take the oath in the first place?

FIRE has certainly seen administrators of professional programs in medicine, dentistry, law — even mortuary science — who deployed ambiguous “professionalism” standards to punish students for otherwise protected speech.

. . .More than 10% of the campus-related cases in which FIRE intervenes now concern requirements that students and faculty demonstrate their DEI commitments or contributions, or personally make land acknowledgements.

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

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

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

I’d add that surely a lot of the students forced to say that they’ll honor all indigenous methods of healing “historically marginalized by Western medicine” certainly don’t believe that, but are nevertheless forces to vow it.  How many of those reciting students accept the curative powers of, say, shamanic rituals?

Here is the summary of the objections in the letter written by Zachary Greenberg, FIRE’s Senior Program Officer for Campus Rights Advocacy, went to Jakub Tolar, the Dean of the Medical School, as well as to the school’s President and General Counsel:

While UMMS may encourage students to adopt these views, the First Amendment bars the university from requiring them to do so. The First Amendment protects not only the right to speak, but the right to refrain from speaking. Requiring new students to “vow” or “commit” to contested political viewpoints violates students’ clear expressive rights, is inconsistent with the role of the university as a bastion of free inquiry, and cannot be enforced at a public institution.

UMMS can require students to adhere to established medical standards, but this authority cannot be abused to demand allegiance to prescribed ideological views—even ones that some students do indeed hold. Specifically, UMMS may not compel students to recite a land acknowledgment, commit to “uprooting the legacy and perpetuation of structural violence deeply embedded within the healthcare system,” or “promote[e] a culture of anti-racism.” Nor may it force students to express a commitment to “embody cultural humility,” or “advance health equity.” Even if written by a group of students, UMMS may not subsequently require all students adhere to these views.

Because students may reasonably perceive recitation of this oath as mandatory, FIRE calls on UMMS to make clear that students may refuse to say it without penalty, and that students will not have to affirm any political viewpoints as a condition of their continued education at the school.

We request receipt of a response to this letter no later than the close of business on October 20, 2022.

My prediction? UMMS will not reply. Will there then be a lawsuit? I don’t think so—unless they find medical students injured by professing what they don’t believe, and what medical student would be plaintiff to such a suit?  But I do think that in future years the school will refrain from such over-the-top vows.

The biomedical importance of sex (and its binary nature)

September 15, 2022 • 12:00 pm

One might almost think, with widespread denial of a sex binary of men and women—a denial that in most animal groups is both fatuous and ideologically motivated—that there are no average biological differences between men and women. “Blank slaters” tend to outright deny the existence of behavioral or cognitive differences between men and women, often doing so on the erroneous grounds that “some women are in the range of men’s scores and vice versa”. In such cases the concept of averages seems to have slipped their minds.

But as the dogs bark, the caravan moves on. Increasingly recognizing the biological and medical differences between men and women—note the implicit recognition of dividing up the species into two sexes— funding institutes and journals dealing with illness and medicine (as well as  are increasingly recognizing the importance of studying men and women separately (or partitioning the data by sex) in biomedical work. That includes using model organisms such as mice, which may show related sex differences. This is the topic of the new feature in the journal Nature shown below. Click on the screenshot to read (it’s free).

 


First, some indicators that dividing up test subjects by sex can give useful and potentially lifesaving results:

Many of science’s gatekeepers — granting agencies and academic journals — feel the same way. Over the past decade or so, a growing list of funders and publishers, including the US National Institutes of Health (NIH) and the European Union, have been asking researchers to include two sexes in their work with cells and animal models.

Two major catalysts motivated these policies. One was a growing recognition that sex-based differences, often related to hormone profiles or genes on sex chromosomes, can influence responses to drugs and other treatments. The other was the realization that including two sexes can increase the rigour of scientific inquiry, enhance reproducibility and open up questions for scientific pursuit.

When studies do include two sexes, the results can be important for health. For example, sex is known to affect people’s responses to common drugs, including some antibiotics. . .

And here are some important biomedical differences already detected:

. . .Despite the bumpy ride, the federal guidelines that were put into place in the early 1990s have led to some important medical discoveries, perhaps a signal that key revelations could emerge from basic research in a few years.

For instance, there are sex-based differences in the heart’s electrical response to several classes of drug, including antidepressants and antibiotics. As a result, sex-based dose adjustments are now recommended for some drugs.

Steroid hormones such as oestrogens and androgens are thought to be primary actors in many of these differences between men and women. For example, women metabolize propranolol, a blood-pressure drug from a class known as beta blockers, more slowly than men do. Researchers think that sex-related steroid hormones acting on the liver can exert these effects. Other factors could include body size and composition, such as the fat:muscle ratio, which tends to be higher in women.

The cut-offs for risk might also differ between men and women. A 2021 analysis of cardiovascular risk related to systolic blood pressure shows what happens if data for two sexes are pooled rather than analysed appropriately. The authors found that when data were pooled, the range for increased risk was a systolic pressure of 120–129 millimetres of mercury (mmHg). But the sex-specific analyses showed that for women, the risk actually begins to climb when systolic blood pressure tops 110 mmHg. If other studies solidify these findings, the result would be a sea change in risk calculation for cardiovascular disease.

That study, as it happens, “was very much inspired and motivated by an NIH request for applications” about sex differences in health outcomes, says Susan Cheng, a cardiologist at Cedars-Sinai Medical Center in Los Angeles, California, and senior author on the report. Without that call for studies specifically designed to look for sex differences, she says, “we had a lot of ideas, but not a thematic focus”. Their findings that men and women differ in risk cut-offs “was actually a real ‘eureka moment’”, Cheng says. “I was like, ‘how did we not see this before?’.” She attributes the results to the NIH’s challenge. “They made it all happen.”

And good for the NIH!

Now surely you can’t attribute all these differences to “socialization,” as the disparity in hormones is based on genes that are differently activated in men and women. Of course, differences in biology due to any factor, like the Patriarchy, still need to be studied for their biomedical effects. But it’s foolish to attribute everything like the above, including the response of the heart to drugs, to environmental influences.

And, of course, if there are no differences between the sexes with respect to a biological trait or response, we need to know that too! This is true for any groups that a priori may differ biologically, but men and women are the most obvious and least ambiguous grouping.

The article highlights some problems with past research, including an apparent lack of knowledge by investigators about how to use statistics to judge the effects of sex, including the simple dictum of using half men and half women in a generalized test on “the population”.  Below is one chart from the paper partitioning 147 biomedical studies starting in 2019. As you see, more than third of them (55) didn’t even consider sex as a factor to study (and that’s dead easy), more than a third (60) didn’t look for interactions between sex and treatment (essential if you want to know if a treatment works differently in men than in women), and only 32, or about 22%, looked for interactions between treatment and sex (16 of these reported a significant interaction, and 10 a nonsignificant interaction).

Finally, even when sex differences were found, as in the red group that didn’t look for interactions, most studies that found a difference didn’t test that difference statistically. The blue group is the one that used statistical tests, but even in that moiety, 6 tests didn’t report the results and one non-significant result was erroneoously reported as a difference.  I thought biomedical researchers would be more savvy than this.

Now there’s a few gestures in the paper toward the “sex isn’t binary” trope by bringing in gender. For example:

The publishing community is pushing for similar clarity. In 2016, it published the Sex and Gender Equity in Research (SAGER) guidelines, which set out how to report sex-based differences in published research. Individual publishers, including Springer Nature (which publishes Nature), have their own policies encouraging researchers to report results by sex, defined as a cluster of biological traits, and sometimes also gender, which is socially defined.

Since “gender” is a social construct, and progressives say there are a gazillion of them, I don’t see how you can report results by gender unless you lump everyone besides men and women as “other”. (I won’t quibble with “sex defined as a cluster of biological traits”, which is technically incorrect but good enough for the purposes of biomedical research.)

And this is thrown in as well, seemingly out of nowhere:

Defining sex as a crude binary, predicated on the chromosomes present, or on specific anatomy, could be too limiting. Some species, such as the nematode worm Caenorhabditis elegans, have one sex that makes only sperm cells and one that makes both sperm and egg cells. And in a vast assortment of species, sex is determined environmentally rather than chromosomally. And still other species can change sex during their lifetime. Placing cells, tissues or even whole organisms into a pair of categories takes on layers of difficulty in these contexts.

Note the pejorative adjective “crude,” meant, I think, to disparage the binary.  Once again they send in the clownfish, nematodes, and turtles, but these don’t refute the idea of separate sexes. Nematodes can be either males or hermaphrodites, the latter being both male (making sperm) and female (making eggs), some clownfish can change from male to female if the alpha female dies—but there are still two sexes, and temperature-specific sex determination, as occurs in many turtles, still gives you males and females. In that case the two sexes are developmentally channeled via an external stimulus rather than via chromosomes and genes, but there are still men turtles and women turtles. (Why some species do this is still not well understood).

 

The fact remains that these species do not show more than two sexes, that they are in the minority of vertebrates and in an even smaller minority of birds and mammals, and, in the end, humans aren’t clownfish, turtles, or nematodes.

Besides emphasizing the valuable lesson that men and women are biologically different in ways that can be important for medical treatment, this article also shows us that where it really counts, where the rubber meets the road—that is, when lives are at stake—the palaver about the binary of sex being a fiction vanishes.

None of this, of course, is intended to ignore those who have disorders of sex determination or transsexuals who have had hormone therapy or surgery, for those patients may need separate study rather than lumping them into one sex or another. That will be hard to do given the paucity of such people, but everyone deserves the best treatment that science can offer.

Lawsuits impending against Tavistock

September 5, 2022 • 1:15 pm

As I’ve mentioned before, London’s Tavistock Gender Identity Development Service (GIDS) has been dismantled after a report by Dr. Hilary Cass that found serious missteps, weaknesses, and evidentially unsupported treatments of gender dysphoric children. Tavistock’s services will be farmed out to other centrs, with a concurrent de-emphasis on the rush-to-judgement form of “affirmative care” (i.e., believe the child and get doctors and therapists to simply facilitate a hoped-for sex transition), as well as a deemphasis on the use of surgery, hormone therapy, and puberty blockers.

This is in line with what other European nations are doing: pulling back from the no-holds-barred form of affirmative care, raising ages at which adolescents can get drugs or surgery, and using puberty blockers, whose safety has not been demonstrated, only in clinical trials. In those countries, it was the unevidenced medical and psychological care that led to the pullback, while in the UK it’s it’s not only that, but the threat of lawsuits against Tavistock, as I discussed in an earlier post.

The lawsuits, as the notice below indicates, are now a reality. Of the 19,000 young people treated at Tavistock, over 1,000 of them may bring lawsuits against the GIDS via “Pogust Goodhead,” an international litigation firm specializing in group claims.  The piece below allows you to start filing a claim, and I doubt readers here will be doing that, but it also outlines the basis for claims, which is of more interest. Click to read:

I’ll just reproduce the section, “What is the case about?”:

The Tavistock clinic opened in 1989 as the UK’s only dedicated gender identity clinic for children and young people. Prompted by concerns from patients, parents, and clinicians at the clinic, the NHS commissioned an independent review of the GIDS service.

The Cass Review’s interim report in 2022 made a number of recommendations on how the service can be changed and improved. Following the findings of the review, the GIDS Clinic at Tavistock is set to close in Spring 2023 and will be replaced with regional centres.

It is expected that localising services to regional hospitals will result in much needed improvements to standards of care and treatment and reduce lengthy waiting lists.

The report raised a number of concerns, including the lack of a consistent clinical approach to assessing the correct treatment pathway for individuals.

Members of staff at the Tavistock clinic reported pressure to adopt an ‘affirmative and unquestioning approach’ to children and young people reporting feelings of gender dysphoria.

Consequently, there are concerns that some children and young people may have been referred down the path of hormonal treatments, without adequate counselling taking place to understand the background of their feelings of gender dysphoria. The report addresses the issue of ‘diagnostic overshadowing’ meaning that other health conditions may have been overlooked.

As a result, some children and young people have been prescribed hormonal treatments before it was established that this was the appropriate treatment for them.

Service Specifications set by NHS England recommends at least 3-6 appointments at the initial assessment stage, Following this an assessment report and care plan should be produced.
Without a proper assessment process some children may have been misdiagnosed or other health conditions have been missed resulting in delays in being sign posted to the appropriate services.

Studies suggest that a number of children who attended the GIDS clinic later regretted the decision and subsequently wish to de-transition.

If you have concerns about your (or your child’s) clinical experience at GIDS at Tavistock or if you believe you should never have been prescribed hormone treatment in the first place, please get in touch with our lawyers who will be able to help and guide you through the process.

In other words, Tavistock is being accused of a form of medical malpractice: rushing first to judgment and then to treatment.

I don’t know how successful these lawsuits will be, but I doubt that this firm, which has a good record of successful litigation, would instigate such a large-scale lawsuit unless they thought they had a good chance of winning, whether it be in the courts or via settlements.  Let this be a lesson to those Americans and American organizations who are huge advocates of “affirmative care.” As I said, money talks louder than anything in America, and if we’re to assure that gender dysphoric children get thoughtful and empathic treatment, only the threat of lawsuits will do that.  Even ideology must bow before Mammon.

Is this a valid exception to protected free speech?

September 4, 2022 • 11:20 am

Here’s a case where one might want to suppress speech in apparent violation of the First Amendment. But after due pondering, I don’t think it’s a good idea. But I waver, as you’ll see, and even though I come down against the bill, as it may be a bad precedent, I am not sure of my stand.

This has to do with a new California law (not yet signed by Gavin Newsom) that punishes physicians who contradict conventional wisdom about Covid-19, with some of that wisdom specified by law. It applies to words, not to actions.

I found this bill through note and links sent by reader Gary, who said this:

I’ve seen very little discussion of California Assembly Bill 2098.  The intention of the bill is good, as are many attacks on free speech, but I, and perhaps you, feel that curbing free speech is generally not the best solution.  Under AB-2098, passed in the California Assembly and Senate, but not yet signed by the governor, physicians and surgeons would face disciplinary action if they voiced an opinion contrary to certain facts about COVID-19 and the associated vaccines as determined by the legislature.  The disciplinary action could include revoking their license to practice.  I despise misinformation and disinformation, but the solution in my opinion, is not punishing those who disagree with the scientific consensus.   The solution is the spread of solid information, not the attempted squelching of misinformation.
I think that this bill is going to the governor’s desk with very little discussion or notice.  He has three weeks to sign the bill, but hasn’t made his position public.   If you think it’s important, you may want to include it in your website.
I’ve put the meat of the bill below. It calls for licensing boards, which are arms of the government, to take action against doctors who “disseminate misinformation or disinformation related to COVID-19, including false or misleading information regarding the nature and risks of the virus, its prevention and treatment; and the development, safety, and effectiveness of COVID-19 vaccines.” In other words, this involves the government suppressing speech, an apparent violation of the First Amendment. But does it fall under the few court-allowed forms of speech that are NOT protected by that Amendment?
The seven points leading to this Diktat are below. These are pretty well established, but they are not absolute facts, as no scientific assertion is beyond questioning. For example, the statement in (c) about the safety and efficacy of COVID-19 vaccines is the best guess we have, but do we know the long-term effects of the vaccines? No, as they’ve been around for only two years. And remember that our knowledge about this disease and about the vaccines, changes almost week by week. Yes, it’s an attempt to protect the health of the public by squelching speech, just as “hate speech” laws are attempts to protect the feelings of the people.

But have a look at the text of the bill from the link above:

LEGISLATIVE COUNSEL’S DIGEST

AB 2098, Low. Physicians and surgeons: unprofessional conduct.

Existing law provides for the licensure and regulation of physicians and surgeons by the Medical Board of California and the Osteopathic Medical Board of California. Existing law requires the applicable board to take action against any licensed physician and surgeon who is charged with unprofessional conduct, as provided.

This bill would designate the dissemination of misinformation or disinformation related to the SARS-CoV-2 coronavirus, or “COVID-19,” as unprofessional conduct. The bill would also make findings and declarations in this regard.

THE PEOPLE OF THE STATE OF CALIFORNIA DO ENACT AS FOLLOWS:

SECTION 1.

The Legislature finds and declares all of the following:

(a) The global spread of the SARS-CoV-2 coronavirus, or COVID-19, has claimed the lives of over 6,000,000 people worldwide, including nearly 90,000 Californians.

(b) Data from the federal Centers for Disease Control and Prevention (CDC) shows that unvaccinated individuals are at a risk of dying from COVID-19 that is 11 times greater than those who are fully vaccinated.

(c) The safety and efficacy of COVID-19 vaccines have been confirmed through evaluation by the federal Food and Drug Administration (FDA) and the vaccines continue to undergo intensive safety monitoring by the CDC.

(d) The spread of misinformation and disinformation about COVID-19 vaccines has weakened public confidence and placed lives at serious risk.

(e) Major news outlets have reported that some of the most dangerous propagators of inaccurate information regarding the COVID-19 vaccines are licensed health care professionals.

(f) The Federation of State Medical Boards has released a statement warning that physicians who engage in the dissemination of COVID-19 vaccine misinformation or disinformation risk losing their medical license, and that physicians have a duty to provide their patients with accurate, science-based information.

(g) In House Resolution No. 74 of the 2021–22 Regular Session, the California State Assembly declared health misinformation to be a public health crisis, and urged the State of California to commit to appropriately combating health misinformation and curbing the spread of falsehoods that threaten the health and safety of Californians.

I’ve put in bold below the two definitions that make me waver about opposing this bill.

SEC. 2.

Section 2270 is added to the Business and Professions Code, to read:

(a) It shall constitute unprofessional conduct for a physician and surgeon to disseminate misinformation or disinformation related to COVID-19, including false or misleading information regarding the nature and risks of the virus, its prevention and treatment; and the development, safety, and effectiveness of COVID-19 vaccines.

(b) For purposes of this section, the following definitions shall apply:

(1) “Board” means the Medical Board of California or the Osteopathic Medical Board of California, as applicable.

(2) “Disinformation” means misinformation that the licensee deliberately disseminated with malicious intent or an intent to mislead.

(3) “Disseminate” means the conveyance of information from the licensee to a patient under the licensee’s care in the form of treatment or advice.

(4) “Misinformation” means false information that is contradicted by contemporary scientific consensus contrary to the standard of care.

(5) “Physician and surgeon” means a person licensed by the Medical Board of California or the Osteopathic Medical Board of California under Chapter 5 (commencing with Section 2000).

This is what I wrote back to Gary:

I’ll have a look, but remember that the scientific consensus changes rapidly, and who is the legislature to determine what the correct “facts” are? And will they then punish doctors for giving out information about diet, etc. that contradicts the legislature? There’s no end to this, and I’m a bit wary of legislating what information is “absolute truth that cannot be contradicted”.

And I stand by my claim that the government should not be in the business of what doctors say about COVID-19, even if it goes against a world of conventional wisdom. This is freedom of speech, even if emitted by a doctor. Or are they allowed only to pronounce on items not related to medicine, or parrot the latest consensus?

It’s a different matter, however, if a doctor acts in a reckless way, violating professional standards like injecting patients with some Trumpian nostrum to cure COVID-19. In that case it is action, not talk, that causes harm, and boards should have the write to examine a doctor’s conduct and, if necessary, punish them or take away their licenses. Likewise, hospitals should be able to fire them. False advertising, too, is illegal, so a doctor is liable to sanction if he or she advertises cures that are known or demonstrated to be bogus. But advertising is not the same as a doctor simply making a pronouncement. Advertising is luring in patients under false pretenses.

Now I am sort of on the fence about this one, for “disseminating information to patients that you know is false, and doing so with malicious intent”, is indeed malpractice. But that’s already covered by the law.  How can you prove that a doctor is doing this with “malicious intent or an intent to mislead”?

This is the same distinction that we see between saying hurtful and “harmful” words like “gas the Jews” or “Jews are acquisitive and in a conspiracy to dominate the world”, which is harmful but legal speech, and causing actual physical harm by hitting someone or inciting predictable and immediate violence against them. The one difference is that patients tend to take their doctor’s advice. But sometimes doctors give bad advice, which is why we urge second opinions on serious matters. A doctor may give bad advice, like “you’d be better off having three stents put in now,” but to me that’s not illegal unless the doctor means it maliciously. The doctor must intend to do harm, and carry that out by treating the patient. And intention is what is nearly impossible to prove in this bill.

To me this bill seems good on the face of it, but creates a precedent where the legislature decides what medical facts are acceptable, and what opinions cannot be uttered. Just remember how advice on diet (and smoking) has changed just in my lifetime.  Let’s leave this to the consensus of doctors and their professional organizations, and let it apply only to actions, not to words.

I’m sure some readers will disagree with me, and that’s fine. Have your say below. As I said, I’m of two minds about this bill.