Gun Insurance: Our Best Shot for Reducing Mayhem

The blue columbines opened on my terrace. They’re among the first plants to flower each Spring, and their deep color and unique bird-like shapes are a cheery signal that winter has gone its way, and the season of renewal is upon us.

But this first flowering also strikes a discordant note because for me the word “columbine” inevitably evokes “Columbine High School,” and the horrific day in April 1999 when two Colorado teenagers walked into their school armed with 9mm semi-automatic weapons, and murdered 12 of their classmates and one of their teachers, for no apparent reason.

At the time, news of this massacre sent shockwaves through a bewildered nation: how was it possible that two kids could become so alienated, so angry that they would plan out and enact a wanton shooting spree and then kill themselves?

The media churned out speculations and analyses. Experts attempted to deduce motives. Political leaders wrung their hands and voiced condolences, along with impassioned affirmations that we as a nation “must do something” about gun control.

Mass shootings no longer shock us the way they did in 1999. They’ve become too common.

In the 24 years since Columbine, there have been 377 school shootings, according to the Washington Post. Over 349,000 kids nationwide have experienced gun violence in the places they go to learn. 

In 2023 alone, there have been 245 mass shootings, according to the Gun Violence Archive. That’s roughly 12 per week, on average, and the year’s not even half over.  And these are the incidents that get reported.

And that’s in addition to the hundreds more mass shootings—generally defined as incidents involving guns that result in the deaths of four or more people, not including the shooter(s)— in other public places like supermarkets, cinemas, nightclubs, and banks. 

In 2023 alone, there have been 245 mass shootings as of the Friday before Memorial Day weekend, according to the Gun Violence Archive—an independent non-profit that collects daily data from 7,500 law enforcement, government, and media sources. That’s roughly 12 per week, on average, and the year’s not even half over.  And these are the incidents that get reported.

Each mass murder generates a surge of by-the-minute news flashes, then a predictable canon of motive-mongering, displays of political piety, and detailed analyses of how it all happened, who did what, and who’s to blame. Then comes the redundant roar of arguments about gun control vs gun rights.

And then it all quickly fades into the blur of previous incidents—the Covenant School in Nashville, the Old National Bank in Louisville, the Tops grocery store in Buffalo, Club Q in Colorado Springs, the Star Ballroom near Los Angeles, Richneck Elementary School in Newport News, Pulse Nightclub in Orlando, the Mandalay Bay Resort in Las Vegas….Uvalde, Sandy Hook, and on and on.

A Public Health Crisis

The headline-grabbing massacres are on top of the staggering stats on gun-related incidents that involve fewer than four victims. According to a comprehensive 30-year review published last November in JAMA Open, there have been more than 1.1 million firearm-related fatalities in the US from 1990 to 2021. This includes intentional homicides, suicides, and unintentional or accidental gun deaths.

Gun-related mortality has increased by 46% since 2004, from a low of roughly 10 per 100,000 citizens to a peak of nearly 15 per 100,000 in 2021 (Rees CA, et al. JAMA Open Netw. 2022).

Eric Fleegler, MD, MPH, a professor of pediatrics and emergency medicine at Harvard, and one of the study’s authors told Holistic Primary Care that if other any disease showed a steady mortality increase of the magnitude we’re seeing with gun violence, it would spark a major public health response.

Gun-related mortality has increased by 46% since 2004, from a low of roughly 10 per 100,000 citizens to a peak of nearly 15 per 100,000 in 2021.

Rees CA, et al. JAMA Open Netw. 2022

In fact, the gun violence issue has elicited strong statements from several medical organizations. The American Public Health Association has deemed it, “a major public health problem and a leading cause of premature death.”  In its 2018 position paper, the American Academy of Family Physicians states: “Gun violence is a national public health epidemic that exacts a substantial toll on the US society.”

AAFP joined the American Academy of Pediatrics, American College of Physicians, American College of Obstetricians and Gynecologists, and the American Psychiatric Association in a call-to-action, demanding that the president and congress:

• Label violence caused by the use of guns as a national public health epidemic.
• Fund appropriate research as part of the federal budget.
• Establish constitutionally appropriate restrictions on the manufacturing and sale, for civilian use, of large-capacity magazines and firearms with features designed to increase their rapid and extended killing capacity.

Those are noble intentions. But like many such statements in the past, they’ve done little to stem the tide of gun-related bloodshed. As Rees, Fleegler, and colleagues show in their study, gun violence has increased since the Covid pandemic all over the country.

Half Measures

Last Spring, President Biden signed into law the Bipartisan Safer Communities Act which increased funding for community-based mental health services, and expanded background checks for gun purchases by individuals under age 21, and bolstered states’ rights to impose “red flag” rules preventing gun purchases by people with histories of violence or severe mental illness.

The bill is notable because it is the first significant piece of federal-level gun legislation in 30 years, and because it was introduced in the Senate by Marco Rubio (R-FL) and endorsed by 15 Republican senators.

In March of this year, the Biden administration issued an executive order calling for near-universal background checks, wider use of “extreme protection orders,” tigher regulation of gun industry marketing tactics, and strengthening of law enforcement efforts to reduce the number of firearms “lost” or stolen during shipping.

These efforts are commendable. There’s no question that we need better mental health services, and tighter control on who’s able to obtain guns.

It’s the Bullets

But these measures—like much of the dialog about gun control—miss an important truth: it is not the guns themselves that kill and maim, it’s the bullets. If we truly want to do something about our heinous rates of violent deaths, we need to regulate access to ammunition.

And there’s a simple, market-based way to do that: Mandate gun-owner’s insurance in all 50 states, and require proof of insurance for ammunition purchases.

Now, if you’re a long-time HPC reader, you probably know that I’m not a big fan of the insurance industry. In healthcare, insurance has morphed into a ravenous profit-driven monster that all-too-often denies people the care they need, while making physicians so miserable that one in every five doctors is contemplating a career change.

But in the context of liability for gun violence, I strongly believe an insurance-based approach, especially if coupled with restrictions on ammo purchase, could potentially align financial pressures to keep lethal hardware out of the hands of irresponsible, dangerous people.

A Middle Path

Gun rights advocates claim—and rightly so—that the overwhelming majority of American gun owners are responsible people who keep firearms to protect themselves and their families, or for hunting, or simply as a hobby. 

Gun liability insurance, coupled with requirements to prove that one’s guns are insured before buying ammunition is one very practical way for gun owners could prove they are, in fact, responsible. It would simultaneously provide a strong financial backstop to cover the medical and ancillary costs in case a 6-year-old kid happens to get hold of Daddy’s 9mm, takes it to school, and shoots his teacher.

It is not the guns themselves that kill and maim, it’s the bullets. If we truly want to do something about our heinous rates of violent deaths, we need to regulate access to ammunition.

And as long as we’re on the subject of medical costs, who does pay for the costs of care when people are wounded in a mass shooting? Who does pay to support families whose loved ones are killed? It’s not the NRA.

What I’m suggesting here is a “middle path” approach, one that balances the constitutional right to bear arms—a right that millions of Americans hold sacrosanct—with the responsibility to ensure that those rights do not infringe upon the safety and wellbeing of others. 

An insurance requirement would not transgress the Second Amendment. It would not involve “taking away” anybody’s guns. It would simply introduce financial accountability into a milieu where, currently, there is very little.

People would still be free to own as many guns as they want, of whatever sort, so long as they are able to pay the insurance premiums. And those premiums would be risk-assessed. A small handgun that a middle-aged woman keeps for protection would not cost as much to insure as a military-grade semi-automatic rifle newly purchased by a 19-year-old kid.

It could be just like automobile insurance—which sets a strong precedent for harm-reduction and accountability via an insurance-based system.

A Strong Precedent

Generally, most people accept the idea that insuring one’s vehicle(s) is reasonable because cars and trucks can, and sometimes do, cause harm to self or others. Likewise, most accept that car insurance premiums vary depending on driver age and experience, type of vehicle being insured, geographic location, past infractions, history of accidents, and other variables. The same principles could be applied to guns—which unlike cars, have no other intrinsic purpose than to injure and kill.

None but the most extreme libertarian considers car insurance to be a Nanny State plot to squelch personal freedom.

This would also be a market-based, financially driven approach to reducing gun violence.

According to Statista’s 2022 data set, roughly 45% of American households own guns, though the figure varies considerably by state.  A recent article in The Guardian claims that Americans have bought more than 150 million guns in the 10 years since the Sandy Hook shooting. According to American Gun Facts, a Second Amendment advocacy group, there are roughly 446 million firearms in the US, and the average gun-owner possesses 5 weapons. AGF notes over 21 million guns were purchased in 2020 alone.

That’s a LOT of potential revenue for insurers. And we all know that the insurance industry likes to make money.

Most people accept the idea that insuring one’s vehicle(s) is reasonable because cars and trucks can, and sometimes do, cause harm. Likewise, most accept that car insurance premiums vary depending on driver age and experience, type of vehicle being insured, and other variables. The same principles could be applied to guns—which unlike cars, have no other intrinsic purpose than to injure and kill.

Largely Untested

But an insurance-based system would require a top-down federal mandate. All 50 states would need to enact and enforce it at the same time, or people in insured states will simply go to uninsured states to purchase their hardware and ammunition. Patchwork efforts would do very little.

Given the current state of partisan politics in Washington, such a mandate—even if it were proposed—is a distant dream.

At the same time, some political observers say that Americans, regardless of party affiliation, have seen enough carnage to finally bring the gun control issue to a new tipping point.

Gun liability insurance is not a new idea, but it is largely untested.

A 2013 New York Times article notes that at that time, several states were toying with the idea of insurance requirements for gun ownership, though none of these efforts came to fruition.

In February 2022, the San Jose, CA city council ratified a law requiring gun owners residing within the city limits to insure their guns—either through a specific gun policy or as part of their homeowner’s insurance– against deaths or injuries caused by accidental discharges. According to CNN, there are 50,000 to 55,000 gun households in San Jose.

The move represents the first such law in the nation, and while it’s an important symbolic step, it is unlikely to have major impact. It a very local measure; it only applies to liability from unintentional injuries; there’s no requirement for proof of insurance to access ammunition; and its implementation has, not surprisingly, met with opposition from gun rights groups (though a federal judge recently upheld its constitutionality).

Gun liability insurance, coupled with requirements to prove that one’s guns are insured before buying ammunition is one very practical way for gun owners could prove they are, in fact, responsible.

Beyond the San Jose experiment, a large-scale insurance-driven approach has never even been tried. But Washington Post writers Jason Abaluck and Ian Ayres believe that the concept could have greater public traction now.

In their excellent 2022 article, The Case for Mandatory Gun-Liability Insurance, they state: Gun insurance would accomplish two goals: First, it would raise the cost of gun ownership for people whose firearms are deemed relatively more likely to be used in crimes (by themselves or others), based on an assessment of risk factors made by insurance companies. That would make those people less likely to obtain guns in the first place. Second, it would provide a strong financial incentive for gun owners to keep these weapons out of the hands of people who might commit crimes with them.”

Abaluck and Ayers add that, compared with other regulatory measures such as all-out bans on certain classes of weapons, an insurance-driven system “might win support from conservatives looking for a market-based approach that wouldn’t have much impact on responsible gun owners.”

“When you apply for homeowner’s insurance, they will ask whether you have a swimming pool, trampoline, or an aggressive breed dog. If you apply for life insurance, the agent is going to ask whether you smoke, are overweight or whether you’re a private pilot. They will ask if you scuba dive. But they won’t ask if you keep a firearm in your home or how it’s stored.”

““`Kristen Moore, University of Michigan

Again, the car insurance analogy is helpful. Arguments against a reasonable gun insurance mandate are easily flipped: “Oh, so you prefer irresponsible gun ownership and total lack of accountability for possession of something that is designed to maim or kill? Well, why should we bother to have car insurance? Why are businesses required to have insurance against harm to customers or to the public?”

Viewed rationally, within the context of the broader principles of liability insurance, the objections don’t really hold up.

Do the Numbers Add Up?

The bigger question is whether insurance companies would see enough potential profit to justify a long and ugly wallow into the quagmire of gun politics. Given the sheer numbers of guns and gun owners, it seems like they’d have incentive. But so far, insurers have stayed away from the gun issue.

Do a Google search for “gun insurance” and you’ll come up with lots of hits. But they’re for policies to insure the worth of gun collections in case they’re damaged or stolen. Policies that insure against liability for harm caused by guns are very, very hard to find.

University of Michigan mathematician Kristen Moore, PhD, who researches firearm trends, says that by and large insurers have taken a “don’t ask” stance toward guns.

“When you apply for homeowner’s insurance, they will ask whether you have a swimming pool, trampoline, or an aggressive breed dog. If you apply for life insurance, the agent is going to ask whether you smoke, are overweight or whether you’re a private pilot. They will ask if you scuba dive. But they won’t ask if you keep a firearm in your home or how it’s stored,” she said in a 2018 interview.

Moore, an advocate for gun liability insurance, goes on: “You pay a premium increase if you have a trampoline and a premium increase if you have a swimming pool, but there are measures you can take to ameliorate that risk. You can fence in your pool, for example. Perhaps the same could be done for firearm ownership. If you take a safety training class, or if you have a gun safe, then there might not be as much of a premium increase.”

To the extent that they’ve said anything about it, the insurance industry’s main objection to gun liability insurance seems to be that insurers don’t want to be on the hook for intentional acts of violence by gun owners. In other words, they see gun ownership as high risk.

That alone speaks volumes, and it’s all the more reason why we need some type of system of enforced responsibility.

This would be a “middle path” approach, one that balances the constitutional right to bear arms—a right that millions of Americans hold sacrosanct—with the responsibility to ensure that the exercise of this right does not infringe upon the safety and wellbeing of others.

Moore underscores the fact that gun violence already costs insurers. “People don’t think about this, but the Columbine mass shooting resulted in a homeowner’s liability claim. The Newtown mass shooting resulted in a homeowner’s liability claim. Insurance executives have estimated that the Vegas shooting will result in a billion dollars in claims across multiple lines of insurance.”

Perhaps these occurrences are happening often enough that insurers might now see the potential to make money from gun premiums as a way to offset the massive payouts.

Aligning Incentives

Over the past year, I’ve talked to many people in diverse professions, and from various walks of life about the general idea of gun owner’s insurance coupled with requirements for proof of insurance before purchasing ammunition.

Most view the core principles as sound and sensible, though all agree that politically, any sort of gun control measure would meet with furious opposition from Second Amendment extremists, some of whom have gone so far as to call for abolition of the federal Bureau of Alcohol, Tobacco, and Firearms in its entirety.

To the extent that they’ve said anything about it, the insurance industry’s main objection to gun liability insurance seems to be that insurers don’t want to be on the hook for intentional acts of violence by gun owners. In other words, they see gun ownership as high risk. That alone speaks volumes.

Harvard’s Dr. Fleegler says, gun liability insurance, “Makes enormous sense. If you get a trampoline in your yard, or a pool, the insurance companies will raise your rates. These things have injury rates much lower than guns.”

Even if major insurers were to support a movement toward gun liability, implementation of such a system would face logistical challenges beyond the inevitable pushback from gun rights extremists.

As Abaluck and Ayres point out in their Washington Post piece, such a system would depend on insurers having access to gun trace data, and that would require changes to the so-called Tiahrt amendments included in Department of Justice appropriations bills since 2003. These amendments block anyone but law enforcement agencies from receiving information obtained from gun traces done by the Bureau of Alcohol, Tobacco, Firearms and Explosives.

It is true that setting up an entirely new insurance-based system for responsible gun ownership and ammunition access would face daunting difficulties. But we desperately need a new approach to a social and medical problem that is raging out of control. The alternative is more mayhem, followed by more ineffective pontificating.

Gun insurance won’t entirely solve the problem of gun violence. It won’t address economic disparities, the epidemic of mental illness, or the nation’s cultural obsession with violence as a preferred means of problem-solving.

There will always be black market weapons, “ghost gun” assembly kits, and 3D-printed weapons. And if gun insurance is mandated, there will inevitably be people who shirk the laws just like there are people who now drive uninsured vehicles.

But a comprehensive system of gun liability insurance could potentially drive greater accountability and responsibility through financial incentives and penalties, the one language that everyone seems to respect.

It’s a middle-road, market-based, potentially bipartisan approach that does not involve banning anything or infringing on constitutional rights. For reducing the horrific burden of gun-related death and disability, it just might be our country’s best shot.

A few weeks ago, I was in a wine store. I went to the checkout counter with my selections, and the cashier asked for my ID. I’m a few decades past age 21, as my grey beard proudly announces wherever I go. So, I was quite surprised to be carded. The cashier proceeded to scan my driver’s license, which struck me as very strange.

When I asked what was going on, she said she’s required to scan everyone’s ID—regardless of age—in order to activate the cash register.

I walked out of the store shaking my head, thinking “I wish they had a system like that to control who can buy bullets.”

END

COVID & Doctor Suicide: Converging Epidemics

Doctor suicide is a painful reality that hospitals, clinic networks, and medical schools go out of their way to deny.

But with the emergence of a documentary called Do No Harm, and a surge of media attention following the suicide of Dr. Lorna Breen during New York City’s first COVID peak, healthcare leaders are finally being forced to reckon with the ugly truth that in many institutions, medicine has become a culture of abuse.

American physicians kill themselves at an alarmingly high rate. A least one doctor commits suicide every day in the US, according to research presented two years ago at the American Psychiatric Association’s annual meeting. Investigators at the Harlem Hospital Center in New York conducted a systematic literature review of physician suicides and identified a staggering rate of 28 to 40 per 100,000––more than twice the general population’s suicide rate of 12.3 per 100,000.

The review also showed that doctors have the highest suicide rate among all professions, including jobs in other high-stress fields like the military or law enforcement. 

Those statistics were identified before COVID-19. In 2020, the pandemic is only accelerating existing trends. Stories of medical professionals lost to suicide in the last 5 months are shining new light on long-standing and dangerous shortcomings in our systems of medical education and practice.

A Doctor a Day

The Accreditation Council for Graduate Medical Education (ACGME) estimates that 300 American doctors die by suicide each year. These deaths rarely make the news, are seldom fully investigated, and often go unacknowledged for what they truly are.

Hazards of duty? Part of the deal? Comes with the territory?

Only if that “territory” is the United States.

Medicine is a high-pressure job anywhere. But doctors in other countries are not killing themselves at nearly the rates of their American counterparts. According to a 2019 systematic review by Dutheil and colleagues, US physicians are far more likely to commit suicide than their peers worldwide. Medical suicide rates have been rising in this country over the last decade; in Europe, they’ve actually been decreasing.

Why do so many American doctors and medical students take their own lives? And why aren’t their deaths more widely publicized?

Pamela Wible, MD, a family physician by training, has spent most of the last decade documenting and studying physician suicides.  As a part of that work, she runs a suicide helpline for medical professionals and students. She’s personally documented nearly 1,500 cases since 2012.

Wible believes guilt, bullying, and exhaustion are three leading causes of suicide in medicine. Physicians, med students, and other healthcare personnel are often subjected to abusive, even dangerous, working conditions. Overwork is common; self-care is penalized.

In many hospitals and clinics, the inevitable pressures of medical practice are compounded by conflicting administrative demands, hostile work environments, retaliatory office politics, racial discrimination, and sexual harassment. It all adds up.

“‘Burnout’ is victim-blaming, and deflects attention from the hazardous working conditions that are illegal in any other industry that values safety, and the human rights violations that are rampant in medical education and beyond.”

—Pamela Wible, MD

Hazing & “Pimping”

It begins with the rigors of medical education, and extends through insurance-based medicine’s emphasis on volume over quality. Young physicians in training are frequently subjected to sanctioned abuse and public humiliation in lecture halls and hospital wards. They’re also severely sleep-deprived—itself a form of torture.

For some suicidal doctors, the problems began when they entered medical school. Med students are typically high-achievers accustomed to ranking at the top of their classes. Once in med school though, some feel for the first time in their lives that they might not really be smart enough, tough enough, or brave enough to become “good” doctors.

Within medical culture, there’s a pervasive fear of being weak, unintelligent, or incapable. That fear drives people to hide their mistakes and imperfections and shy away from seeking help, even when it’s desperately needed.

Some level of pressure and anxiety is to be expected in a career as demanding as medicine.  But Dr. Wible sees shockingly toxic elements in US medical culture.

Bullying, humiliation, and hazing are tolerated, sometimes even encouraged as acceptable training strategies. Many doctors can tell stories of getting “pimped,”––an aggressive, rapid-fire style of testing students’ clinical knowledge by asking difficult or intentionally unanswerable questions in class, in the clinic, and even in front of patients.

All that takes its toll.

A 2016 study of med students by the National Institutes of Health and the US Department of State found that, “overall prevalence of depression or depressive symptoms among medical students was 27.2%, and the overall prevalence of suicidal ideation was 11.1%.” Among those who screened positive for depression, only 16% sought treatment (Rotenstein, L et al. JAMA. 2016; 316(21): 2214‐2236).

“There seems to be more mental health distress among first and third-year med students, and definitely for unmatched graduates. In some residency programs, 75% of residents meet criteria for major depression,” Wible says.

Med students experiencing depression, anxiety, or suicidal thoughts avoid seeking care because they worry they’ll be “outed,” stigmatized, and punished if they do.

The stress and pressure––and subsequent mental health risks––only increase once they transition into actual clinical practice. 

They enter an extremely hierarchical system in which they’re often forced to “earn their keep” by filling the most undesirable shifts. Long hours without breaks; weekend and holiday shifts with little time off; isolation from friends, family, and crucial social support—these are not exceptions, but rather the rule for many young doctors.

Sleep Starvation

Sleep deprivation is also a big factor, says Wible. 

Going without sleep for extended periods is comparable to alcohol intoxication. Exhaustion erodes cognitive and motor skills, slows reaction times, and compromises task performance. Doctors who are sleep-deprived are also at heightened risk for motor vehicle collisions and hospital-related injuries.

It is not hard to find a physician who can tell tales of falling asleep, or witnessing colleagues drop unconscious to the hospital floor, while making rounds, treating patients, or conducting surgeries. Perhaps you’ve been one of them.

In other high-stress professions–pilots, air traffic controllers, even truck drivers, for example–there are regulations and work-hour restrictions that limit shift lengths, because everyone recognizes that sleep deprivation and overwork impair performance.

Yet our medical system drives doctors—who routinely deal with matters of life and death that hinge on clear, quick judgment—to the point of exhaustion.

Current ACGME requirements permit interns’ duty shifts to run for 24 consecutive hours––up from a previous cap of 16 hours––and 80 total hours per week. 

Not only do we permit sleep-starved doctors to administer potentially dangerous drugs, monitor patients on a complex array of equipment, and perform surgeries that require great skill––we expect them to do it all flawlessly––and to be nice about it.

In other high-stress professions…there are regulations and work-hour restrictions, because everyone recognizes that sleep deprivation and overwork impair performance. Yet our medical system drives doctors—who routinely deal with matters of life and death that hinge on clear, quick judgment—to the point of exhaustion.

Exhausted doctors are more likely than well-rested ones to make medical errors, which sometimes kill patients. A 2018 Mayo Clinic study found that physicians who made errors were more likely to exhibit symptoms of fatigue, burnout, and recent suicidal ideation (Tawfik, D et al. Mayo Clin Proc. 2018; 93(11): 1571-1580).  

When Epidemics Collide

COVID-19 presented new and unusual stressors for clinicians in viral epicenters like New York City, Washington, DC, and Chicago, where prevalence was highest during the early months of the pandemic.

Emergency medicine physicians and nurses are particularly vulnerable. In centers with very high caseloads they’re working under constant duress, sometimes without adequate protective equipment, in hospitals that were understaffed even before the pandemic. As they treat their patients, they worry about their own risk, and the potential for carrying the virus home to their families.

Dr. Wible, who has provided counselling for suicidal clinicians for nearly a decade, says that since the coronavirus, she’s seen a dramatic increase in the number of calls.

“Volume doubled, and I led group support calls on Zoom to handle the uptick in requests for support,” she reported.

On April 26, Dr. Lorna Breen, a well-respected ER doctor at New York Presbyterian’s Allen Hospital in New York City died of “self-inflicted injuries” at age 49. Her story got the media’s attention, as it represented the convergence of two epidemics: COVID and doctor suicide.

Prior to her death, Dr. Breen had treated many coronavirus patients, and she herself had recently recovered from the virus.

“Make sure she’s praised as a hero, because she was,” Breen’s father, also a doctor, told the New York Times. “She’s a casualty just as much as anyone else who has died.” The elder Dr. Breen also stressed that his daughter, “did not have a history of mental illness.”

In its official public statement, New York Presbyterian used similarly valiant language. “Dr. Breen is a hero who brought the highest ideals of medicine to the challenging front lines of the emergency department.”

But an email to hospital staffers did not immediately identify the cause of Breen’s death, reflecting an attitude of denial and obfuscation that Wible says is the rule, not the exception, among hospital administrators.

Breen’s family and hospital “had to use ‘healthcare hero’ propaganda on her immediately, so that she wasn’t forgotten or thrown to the wind as weak,” Wible told Holistic Primary Care.

“They gave her the hero spin because she was in New York City and had a high position in her hospital. Her family made it clear that she never had any preexisting medical conditions and instead suggested her death was due to the coronavirus, to distance her and the family from the topic of mental health issues.”

This denial contradicts evidence Wible has gathered from the nearly 1,500 cases she has recorded. She finds that ER doctors rank among the top three medical specialists most likely to die by suicide. Psychiatrists, surgeons, and anesthesiologists also have a higher risk than others.

Secondary Trauma

Wible believes secondary trauma plays a big role, at least for the latter two specialties.

Breen’s family insists that she never suffered from prior mental health challenges, but Wible says it’s hard to imagine that a doctor who spent her entire career in the ER never suffered a single blow to her emotional or cognitive wellbeing.

“I believe all emergency medicine doctors have mental health wounds,” Wible said.

It is common to hear clinicians say that experiencing or witnessing a catastrophic injury or illness early in life is what inspired them to pursue medical careers. Wible finds that “many EM doctors have experienced significant trauma in their childhoods––then they go into emergency medicine and are re-traumatized every day.”

Even those who did not experience childhood trauma will invariably incur “occupationally-induced mental health wounds” while working in the emergency department. “If they have not sought appropriate care, then they are still wandering around with those wounds every day,” she said. 

It’s Not “Burnout,” It’s Abuse

“This is tough work, even on the best day,” Wible says of the medical life. “Even in the parts of medicine that seem like they could be happy, there is unforeseen, extreme tragedy.”

In our current systems, the inevitable stresses and pressures of caring for sick, injured, and sometimes dying people, are amplified by factors unrelated to patient care.

Micromanagement by senior doctors or hospital administrators; incessant demands for documentation; veiled threat of punishment or legal consequences for errors; poorly managed and understaffed clinics; incessant time pressures. All these factors leave many physicians feeling not only emotionally exhausted, but cynical towards the profession they once loved.

We call it “burnout.” But Dr. Wible warns that this term obscures the abusive nature of our medical system itself.

“‘Burnout’ is victim-blaming, and deflects attention from the hazardous working conditions that are illegal in any other industry that values safety, and the human rights violations that are rampant in medical education and beyond.” 

Hospitals treat physicians in ways that “break the UN Declaration of Human Rights,” she suggested. Other medical professionals also experience extreme pressure, overwork, and abuse. But statistically, the suicide risk is much higher for physicians.

Hidden in Plain Sight

Part of the problem is physicians’ uncanny ability to hide their suffering not only from colleagues and supervisors, but from family members and friends. Doctors who experience depression, anxiety, or suicidal ideations often view those symptoms as flaws that must never be exposed. Some worry that admitting psychological or emotional distress will call into question their fitness to practice or, worse, might lead to dismissal. 

There may also be expectations from family and friends that someone who has “made it” in such a high-status profession must surely be reaping rewards. Some doctors feel a sense of duty not to disappoint parents, spouses, or other loved ones who’ve also invested and sacrificed to make their medical careers possible.

As a result, few people know when a doctor friend or family-member is contemplating suicide.

Dr. Wible—who had her own struggles with anxiety and suicidality earlier in her career—says there are a few red flags: “Excessively happy doctors are often hiding their emotions and pain.” Additional warning signs may include a recent medical liability case, medical board complaints or investigations, and major life events like divorce.

Denial: A Double Assault

Denial by hospital administrators, family members, and colleagues has only compounded the problem of doctor suicide.

“We create the scenario that takes these wonderful young people and puts them in a situation where they can see the only way out is death––and then we bury their suicides,” Wible said. “It’s like a double assault.”

She pointed out that a number of doctor suicides involving ingestion of prescription drugs were misleadingly reported as “accidental” overdoses. It is certainly possible for physicians to unintentionally take too much medication, but this explanation stretches credibility. MDs get extensive training in pharmaceutical use; that makes them some of the least likely people on the planet to unknowingly over-consume a drug.

Doctors do, however, have ready access to controlled substances, which heightens risk of abuse. According to a 2013 study published in the Journal of Addiction Medicine, 69% of doctors reported that they abused prescription drugs “to relieve stress and physical or emotional pain” (Merlo, L et a. J Addict Med. 2013; 7(5): 349-53).

Physicians also possess an intimate and detailed knowledge of human anatomy, increasing the chances that they will complete a suicide if attempted.

Concealing doctor suicides protects medical schools and hospitals from having to address systemic problems. But sweeping the dirty secrets under the rug only puts other health professionals––and their patients––at tremendous risk.

“Suicide is not the problem; censorship is,” Wible argued. “If we would just speak openly about this crisis, it could be easily solved.” 

Effective, evidence-based suicide prevention tools exist––and they can help avert the needless loss of doctors’ lives. “We have the resources to solve this problem. But if we censor it, we can’t make it better. We can’t solve a problem that nobody is acknowledging.”

Get Up, Stand Up

Wible says that to truly shift medical culture in a healthier direction, “we need to normalize the conversation about suicide risk, just like we’ve normalized conversations about blood pressure.” 

Education is also vital. Two resources she recommends are the documentary “Do No Harm” by filmmaker, Robyn Symon, and her free audiobook of doctor suicide notes, Physician Suicide Letters—Answered, in which she shares her correspondence with numerous clinicians whom she’s helped to avoid suicide.

The key, she says, is providing a forum for self-expression without fear of rebuke or humiliation. “The system of medical education and practice should be set up in a way where people are able to connect with each other honestly, emotionally and spiritually, without punishment,” Wible said.

Fixing the situation will also require system-wide reforms to create more humane working conditions within medical institutions. Wible believes doctors, nurses, med students, and other health professionals need to stand up and fight for those reforms.

To that end, she recently published Human Rights Violations in Medicine: An A-to-Z Action Guide.

The book documents a spectrum of abusive situations–from food and sleep deprivation to threatening foreign-born doctors and trainees with deportation–that routinely occur in American clinics. It also gives guidelines to help doctors chronicle their own experiences of abuse, and practical action steps for confronting and resolving these situations.

Dr. Wible is certainly not the only physician concerned with doctor suicide, and pushing for change.

Keith Frederick, an osteopath who also served for eight years in Missouri’s House of Representatives, introduced a bill to address mental health in Missouri medical schools after learning that a fourth-year osteopathic student in his community died by suicide just days before graduation.

In the film Do No Harm, Dr. Frederick described suicide as an unacknowledged “occupational hazard” in medical settings. During his years as a legislator (2011-2019), he also sponsored a bill requiring hospitals to examine mental illness and burnout among staff.

Not surprisingly, Frederick’s proposal met initial resistance from Missouri medical institutions. The deans of all six of the state’s med schools co-authored a letter urging legislators not to pass the bill.

Ultimately, though, Frederick and his supporters won-out. The “Show-Me Compassionate Medical Education Act” (MO Senate Bill 52) was signed into law in July 2017. It requires medical schools to provide incoming students with information about available depression and suicide prevention resources. It also granted medical institutions the authority to conduct internal research, without penalty, on rates of depression, suicide, and other mental health issues among medical students.

Thank a Doctor, Save a Life

In addition to raising awareness around suicide risk and prevention, expressions of gratitude can literally help keep doctors alive. 

Wible encourages people to “please show appreciation and give thank you cards to your doctors, and ask them how they are doing.”

It might seem simplistic or even silly, but she believes it can be life-saving.

“It can be very hard to reach doctors––they’re often so closed off emotionally. It’s important that they feel validated, normal, and appreciated.” A thank you letter may give a doctor a much-needed dose of positive reinforcement that he or she may not otherwise receive.

Verbal thanks are nice too, but Wible says that penned messages carry an even greater and longer-lasting power. “Thank you notes are huge––especially if they are written. They have a lifespan that goes on for decades––doctors will read and reread them, sit and stare and really soak in the words.” 

Clinics and hospitals might also consider setting up anonymous compliment boxes where staff and patients alike can submit thank you notes to their doctors or colleagues.

She also urges medical practitioners to prioritize their own health and self-care. She herself does this by “spend[ing] a lot of time in nature, hiking, gardening, and with my animals.” She also stressed the importance of strong social connections, like the one she shares with her loving partner.

“And most important,” she added, “I get therapy WEEKLY.”

She holds that all med students and doctors should receive “non-punitive, 100% confidential therapy” every week. Whether it’s for preventive or active treatment, breaking down the barriers around mental health support could help avert the tragic doctor suicides on which our current systems prefer to turn a blind eye.

END

Root Causes in Bone & Joint Health: The Growth Factor Paradigm

Bone and joint health are often reduced to simplistic suggestions, like “take calcium,” “eat more dairy,” or “take something to build collagen.”

But there is so much more to it. Bone is a living, metabolically active tissue in a reciprocal relationship with the joints, and connective tissues.

In this FREE webinar, David Craig, NMD, will share a growth factor paradigm for restoring bone and joint health based on the use of Bone Morphogenic Proteins (BMPs).

Drawing from his decades of clinical experience as a naturopathic physician, as well as his own personal quest to better understand the key factors influencing health and disease, Dr. Craig will explain how BMPs can address the root causes of poor bone/joint health.

During this webinar, you’ll learn about: 

• The root causes of bone health – beyond minerals
• The key determinant of joint health – beyond supplementation 
• The growth-factor connection – essential stem-cell signals
• A growth-factor paradigm for regenerative medicine utilizing Bone Morphogenic Proteins (BMPs)

SPONSORED BY Regenerative Tissue Sciences, the professional sales division of ZyCal Bioceuticals Healthcare Co., Inc

David Craig, NMD earned his doctorate in naturopathic medicine at the University of Bridgeport College of Naturopathic Medicine. This 8-year training program included the internships and ER rotations in conventional allopathic clinics, and classes taught by professors from Yale Medical School, along with intensive education on natural therapies. He has been in private practice for 22 years, specializing in endocrinology, immunology, chronic fatigue syndrome, nutrition counseling, and the identification and mitigation of environmental triggers that can cause the body to become unhealthy.

Women & Autoimmune Disease: An “Xist”ential Question

The statistics have been clear and consistent for decades: autoimmune conditions are at least three times more common among women than men. Some studies suggest it’s more like a factor of four. For specific diseases like Lupus, the disparity is 9-fold. For Sjogren’s syndrome, it’s 19 to 1.

This appears to be an objective biological phenomenon. It’s not a reflection of gender-based differences in seeking medical care, or of misdiagnosis—though there’s plenty of that. Neither is it strictly hormone-related.

Hormonal factors do play some role in autoimmune disorders. But the hormonal differences between biologically female and male individuals in no way fully account for the marked disparity of autoimmune diseases.

In humans, and in rodent models, the simple presence of the double X chromosome is far more predictive of autoimmune risk than any measure of hormone status.

A Vexing Question

What accounts for such a marked gender disparity? It’s a question that has vexed researchers, clinicians, and patients for a long time.

An international research team headed by two dermatologists at Stanford University believe they have an answer, or at least a strong clue.

They contend that Xist—a specific form of long non-coding RNA produced by biologically female mammals—is the decisive factor.

Xist has a very particular function: it squelches gene expression on one of the two X chromosomes in each cell, thereby preventing a lethal doubling of proteins coded by genes within the X chromosome. This X chromosome inactivation occurs during early embryogenesis.

Through a process that appears to be random, each cell in the embryonic female body “decides” which of its two X chromosomes it will inactivate. The one selected for silencing begins to produce Xist, which then binds to and coats the chromosome, thus inhibiting transcription of its genes.

This “decision” is preserved over the lifetime of the individual, through many cycles of cell division, ensuring that all of the cells in the body are only transcribing one set of X chromosome genes into actual proteins.

X Inactivation & Autoimmunity

In humans, Xist is a 19 kb long non-coding (lnc) RNA chain. The length of the chain differs slightly in other mammals, but the function is the same. Biologically male animals have the gene for Xist on their X chromosomes, but under normal circumstances it is never expressed. Production of Xist only occurs when two X chromosomes are a matched pair inside a cell.

So, what does this have to do with autoimmune disease?

Once Xist binds to the X chromosome that will be silenced, a wide range of other types of proteins bind onto Xist, forming ribonucleoprotein (RNP) complexes. It turns out that many of these are autoantigenic.

“Here, we show that the Xist ribonucleoprotein (RNP) complex comprising numerous autoantigenic components is an important driver of sex-biased autoimmunity,” writes lead author Diana Dou, PhD, in the introduction to the Stanford group’s recent landmark report, published in the journal, Cell. 

Dr. Dou is a researcher in the lab of Stanford dermatologist and geneticist, Howard Y. Chang, MD, PhD. Nearly a decade ago, Chang, Dou, and their colleagues identified nearly 100 proteins that can bind to and accumulate around Xist. A more detailed bibliomic analysis showed that 30 of these Xist RNPs had been previously identified as targets for autoantibodies associated with human autoimmune diseases including Rheumatoid Arthritis, Systemic Lupus Erythematosus, Multiple Sclerosis, Myositis, and Sjogren’s syndrome.  

This was not entirely surprising. The authors note that autoantibodies are often directed toward nuclear RNA binding proteins. “The nature and titer of such autoantibodies define the type and severity of autoimmune diseases in clinical practice.”

But the fact that these particular autoantibodies targeted a specific type of RNA complex that binds to the X chromosome, and is normally produced only by biologically female mammals, opened an entirely new line of inquiry about the etiology of autoimmune disease.

“Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity,” they wrote.

This hypothesis was bolstered by the fact that in men with Klinefelter syndrome—a rare genetic condition defined by having one Y and two X chromosomes—the risk of many autoimmune disorders is comparable to that of women. Men with Klinefelter’s are phenotypically male. Though their testosterone levels are usually low, they do show typically male hormone patterns. It seems that in this population, the predisposition to autoimmunity is connected to the presence of that second X chromosome.

Dr. Chang, who is a clinician as well as a researcher, said his driving interest in this question is a desire to help his patients. “As a practicing physician, I see a lot of lupus and scleroderma patients, because those autoimmune disorders manifest in skin,” he said in a Stanford University press release following publication of the new study last February. “The great majority of these patients are women.”

Xist Increases Autoimmunity

To prove that Xist can generate autoimmune responses, the Stanford team assembled an interdisciplinary, international consortium of researchers who, together, undertook some very sophisticated bioengineering.

First, they developed transgenic strains of mice in which the males produced Xist in a similar manner as the females. The particular Xist gene which they inserted into the mouse genome is inducible by external chemical means. In this case, the chemical trigger was doxycycline, which the investigators could give to the mice in drinking water. This gave the them the possibility of turning on or shutting off Xist production in the males. Once induced, Xist forms similar RNP complexes in the males as seen in female mice.

The investigators then injected the test mice with pristane, an irritant that can induce a lupus-like autoimmune reaction in susceptible mice. In this way they could test whether male mice that produced Xist were more likely than normal males to show the autoimmune response.

Indeed, they were. The male mice with activated Xist were far more likely to show autoimmune reactions following pristane stimulation than the non-Xist males. The autoimmune reactions occurred at a rate comparable to that of females similarly stimulated with pristane.

“Increased disease severity and elevated autoreactive lymphocyte pathway signatures were observed in the mouse models of pristane-induced SLE,” the authors report. “Expression of Xist RNPs in male mice is sufficient to increase disease severity and change the expression and epigenomic profiles of both the B cell and T cell effectors of SLE pathogenesis.”

Chang and colleagues note that the presence of Xist alone does not induce autoimmunity; the Lupus-like syndrome still needed to be stimulated by the pristane injection. But the presence of activated Xist in genetically male mice that would not ordinarily express Xist did increase the likelihood and severity of the autoimmune reaction once the pristane stimulus was applied.

The findings give creedence to the core hypothesis that production of Xist, and the subsequent RNP complexes it forms, predisposes an organism to autoimmune reactions.

New Human Disease Markers

On its own, this mouse experiment could be dismissed as a very elaborate science fair project with limited clinical significance. But the Stanford team went a step further: based on the antigens they identified in the mice, they designed an antigen array to test serum obtained from humans with autoimmune diseases, which allowed them to assess reactivity to specific Xist RNP complexes.

Using this array, they were able to compare serum from patients with Dermatomyositis, Scleroderma, or SLE, with samples obtained from healthy donors who did not have autoimmune diagnoses.

They found that the autoimmune patients were significantly more reactive to 79 of the antigens tested than the healthy control subjects. Of those 79 antigens, 53 were associated with Xist RNPs. Nine of the protein complexes tested were antigenic in all three of the disease categories. Further 28 of the 53 Xist-associated antigens had not previously been described in association with specific autoimmune diseases.

“These results show that multiple proteins from the Xist RNPs are novel autoantigens in patients with DM, SSc, and SLE.” This suggests that some of them could eventually become potentially new markers for detecting autoimmune conditions.   

The Stanford research goes a long way in making the case that Xist and its related protein complexes, play a role in the etiology of autoimmune disorders, though it’ll take more work to definitively prove it.

Nature vs Nurture?

The findings are provocative in that they suggest that the strong gender disparity in incidence of autoimmune disorders could be gene-linked, and therefore independent of diet, lifestyle, or environmental factors.

In an interview shortly after publication of the study, Dr. Chang stated: “This research says that the risk for autoimmune disease comes from your genes. It’s not something you did wrong. Sometimes people are like, “Did I eat something wrong? Did I do something wrong?” No. It’s not something you can control.”

That runs somewhat counter to core principles of functional, holistic, and naturopathic medicine which put autoimmunity in the context of modifiable factors like microbiome dysregulation, intestinal impermeability, food allergies, and exposure to things like mold and environmental toxins.

Understandably, the paper generated considerable interest within the functional medicine community.

Terry Wahls, MD, a professor of medicine at the University of Iowa, who reversed her own Multiple Sclerosis via nutritional and lifestyle changes, and has taught MS patients to do the same, described the Stanford study as “Super interesting.”

Though the clinical implications are not entirely clear, Wahls says the paper underscores the broad problem of “not having enough women in studies. A blind spot was created,” she told Holistic Primary Care.

Joel Evans, MD, a functional medicine practitioner specializing in women’s health, says the Xist research prompted a lot of conversation among his peers and colleagues. Though it clearly suggests that predisposition to autoimmunity is X-linked, this is definitely not a clear-cut nature versus nurture dyad. The predisposition may indeed be genetic, but exogenous factors still play a big role in determining whether or not someone will actually manifest an autoimmune disease, Dr. Evans says.

Indeed, while autoimmune conditions are more common in women than men, the majority of women do not have autoimmune diseases despite having an XX genotype and producing Xist RNA. Further, some men do have autoimmune conditions, though they do not produce Xist. In fact, one autoimmune disease—Type 1 diabetes—has a higher incidence in males versus females.

Studies of identical twins show that the development of autoimmune disorders is not always identical in twin pairs, despite the shared genome.

The discovery that Xist-linked protein complexes can function as autoantigens is compelling. It adds a new and very interesting piece to the autoimmune puzzle. But it is not the entire picture.

END

Microplastics: A New Cardiovascular Risk Factor

The presence of micro- or nano-plastic particles in carotid atheromas significantly raises the risk of myocardial infarction, stroke, or death from any cause within 3 years.

That’s the blunt conclusion of a new multi-center study headed by researchers at the Department of Advanced Medical & Surgical Science, University of Campania, Naples, and involving more than 250 at-risk patients undergoing carotid endarterectomy.

Micro- and nanoplastics (MNPs), defined as plastic particles smaller than 5 mm and 1,000 nm respectively, result from the mechanical breakdown of larger plastic objects. MNPs are increasingly found in air, water, soil, and food worldwide.

According to a 2014 estimate, there are between 15 and 51 trillion individual bits of microplastic in the world’s oceans. They’re estimated to weigh between 93,000 and 236,000 metric tons. That was 10 years ago, and that’s not accounting for the much smaller nanoplastics. The problem has only increased since then.

Chronic exposure to MNPs via ingestion, inhalation, or skin contact, is also increasingly common. Over the last decade, researchers around the globe have detected MNPs in human lung, liver, and placental tissue, as well as in blood, urine, breast milk, and feces. They’ve also been found in tissue of wild birds, fish, and mammals.

Animal studies and in vitro models suggest that specific MNPs may be cardiotoxic, primarily because they can trigger oxidation, inflammation, and apoptosis in endothelial cells, and can also induce myocardial fibrosis. Constant MNP exposure has been linked to a number of respiratory, digestive, and immunologic disorders.

Plastic in Plaques

The new study, published in the March 7 edition of the New England Journal of Medicine, is the first human clinical study to provide firm evidence that MNPs are an independent factor for adverse cardiovascular outcomes in at-risk people.

The multicenter team, headed by veteran cardiovascular researcher, Raffaele Marfella, MD, PhD, analyzed atheromatous plaque tissue for the presence of MNPs, using several methods: pyrolysis, gas chromatography, mass spectrometry, stable isotope analysis, and electron microscopy. They looked for 11 specific types of micro- or nanoplastics. Two types—polyethylene and polyvinyl chloride—showed up at high levels in a large number of the patients.

Marfella’s team initially enrolled 312 patients from three different hospitals, all of whom underwent endarterectomies to mitigate the risk associated with advanced though asymptomatic carotid atherosclerosis and stenosis (greater than 70%). Eight of these patients died prior to discharge, and 47 were either lost to follow-up or not available for complete data collection.

The researchers followed the remaining 257 people for a total of 34 months. They tracked incidence of nonfatal stroke, nonfatal myocardial infarction, and death from any cause, distilling these into a composite endpoint.

Well over half of the patients (58.4%) had atheromas containing polyethylene, at a mean level of 21.7 ±24.5 μg per milligram of plaque. Thirty-one (12.1%) also had detectable levels of polyvinyl chloride, at a mean level of 5.2 ±2.4 μg per milligram of plaque.

The authors note that the minute plastic particles were, in fact, visible to microscopists. “Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris.”

The people who carried MNPs were more likely to be male, more likely to smoke, and more likely to be diabetic and severely dyslipidemic than those who did not. But there were no differences between the two groups in terms of body mass index or severity of carotid stenosis. In both groups, the mean age was in the early 70s (71 years old for those with NMPs, 73 for those without).

There were no geographic differences in the prevalence of MNPs based on the locations of the three clinics at which the patients were treated.

A Health Hazard

Beyond the astonishing fact that people these days are exposed to so much plastic that it ends up in their carotid arteries, we must consider the possibility that the presence of microplastics is very detrimental to human health.

Marfella’s data show that compared with subjects who were MNP-free, those who had plastic in their plaques had a 4.5-fold increased risk for the composite adverse endpoint (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001).

The authors stressed that outcomes were logged via reviews of electronic medical records by reviewers who were unaware of the MNP status of the patients in question.

Among the 150 subjects showing MNPs, there were 14 non-fatal strokes, 10 non-fatal MIs, and 6 deaths. Among the 107 people without MNPs, there were only 5 strokes, 2 MIs, and 1 death.

The incidence of stroke, MI, or death from any cause was 20% among the patients with MNPs, versus 7.5% in those without the plastic residues in their arteries. That’s close to a 3-fold difference.

Put another way, the authors calculated there were 6.1 events per 100 patient-years in the MNP subgroup, versus 2.2 events per 100 patient-years in the MNP-free cohort.

Comparable to Diabetes

How predictive is the presence of MNPs for morbidity and mortality? Very predictive, it seems.

Marfella and colleagues stress that their data do not prove that MNPs cause stroke or MI. But their Cox regression analysis showed that the presence of MNPs confers a hazard ratio for adverse outcomes comparable to that of diabetes (4.53 and 4.76, respectively). MNPs were more predictive of adverse outcomes than age, BMI, total cholesterol, and several other common cardiovascular risk factors. 

The Italian researchers also provide further evidence that MNPs are proinflammatory. They measured serum IL-8, IL-1β, IL-6, and TNF-α in blood samples from the study’s participants. They also measured collagen content in the atheromatous plaques, and levels of CD3 and CD68, all of which are indicators of inflammation.

All cytokines increased in correlation with the amount of polyethylene present in the plaque samples, as did the CD3 and CD68 levels. The collagen level went down as MNP levels increased. All of these findings support the notion that MNPs drive proinflammatory pathways in human tissue.

Several previous epidemiological studies concluded that occupational exposure to plastic-related pollutants including polyvinyl chloride can raise the risk of cardiovascular disease. The Marfella provides clinical evidence to bolster that hypothesis.

Direct & Indirect Effects

MNPs may have direct and indirect effects on cardiometabolic health: they can clearly translocate directly into the circulation and into the endothelial tissue, and they may also trigger systemic inflammation which is a key factor in the development and progression of heart disease.

The degree to which MNPs can infiltrate human tissue is largely dependent on particle size: the smaller the particles, the more deeply they are able to penetrate into our organs.

Marfella and colleagues state that the nanoplastic particles they observed in the atherosclerotic plaques from their patients were well below the 200-nm threshold for passage through the gut barrier layer and into the bloodstream.

Ubiquitous & Insidious

This study adds to the groundswell of research in recent years, showing that plastics in our environment—and remember, there are no endogenously produced plastics—are absorbed by our bodies, and that they can affect our physiology.

Two years ago, toxicologists at the Vrije Universiteit Amsterdam published the first study documenting the presence of microplastics in human blood.

Heather Leslie and colleagues had analyzed blood samples from 22 healthy adults, and found plastic residues in 17 of them (77%). Half contained traces of polyethylene terephthalate (PET), a common material for food containers and beverage bottles, and one quarter showed microparticles of polyethylene.

The Leslie study built on earlier evidence, including a 2009 paper documenting plastic additives, especially phthalates, in the urine of 242 pregnant women (Meeker JD, et al. Philos Trans R Soc Lond B Biol Sci. 2009), and a 2019 study showing an average of 20 different microplastics in feces from eight  healthy human volunteers (Schwabl P, et al. Ann Intern Med. 2019).

There are many different types of micro- and nanoplastic. Why were polyvinyl chloride and polyethylene the only ones that Marfella and his team detected in carotid atheromas?

It’s a good question with no definitive answer….yet.

“Studies in animal models suggest that the physicochemical features of different MNPs influence whether they reach distant organs,” say the authors. “Additional work is needed to assess whether polyethylene and polyvinyl chloride accumulate preferentially within plaque and whether they are more pathogenic than other types of MNPs in this regard.”

Another big yet-to-be answered question is whether MNPs are themselves directly atherogenic, or simply absorbed into existing atherogenic plaques without playing any direct role in stimulating plaque formation.  

The presence of MNPs in circulation and in atherosclerotic plaques may also be an indicator of other environmental, dietary, and lifestyle-based risk factors. In other words, it may be a reflection of a generally unhealthy lifestyle.

“The association between the presence of MNPs within plaque and the incidence of a composite of cardiovascular disease or death outcomes may also entail the risk from exposure to other residual, unmeasured confounding variables, such as unknown exposures during the life course of the patient or, more broadly, the health status and behaviors of the patients,” Marfella and colleagues write. They add that this study did not look specifically at diet or lifestyle-related variables.

Modes of Exposure

Polyethylene and polyvinyl chloride, the two types of MNPs that the Italian researchers detected in carotid atheromas, are ubiquitous in modern industrial societies. They’re used to make food and cosmetic containers, water pipes, and a host of common household and industrial items.

MNPs resulting from the breakdown of polyvinyl chlorhide and polyethylene have been identified in drinking water, in foods, and cosmetic products all over the world. Particles of 2.5 μm or less can also be aerosolized, meaning that they can be inhaled, entering the lungs and the blood. Lauren Jenner and colleagues at the Hull York Medical School in the UK, identified polyethylene microparticles, along with polypropylene in lung tissue samples from 13 people (Jenner L, et al. Sci Tot Environ. 2022).

Like many other environmental toxins, microplastics and nanoplastics have the potential to bioaccumulate up the various food chains, with concentrations being highest in apex species, like humans. Some studies have suggested that on their way up the food chain, MNPs absorb and accumulate other toxic substances including persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and pesticides. In other words, they become carriers for other potentially problematic substances. (Lithner D, et al. Sci Tot Environ. 2011; Koelmans AA, et al. Environ Sci Tech. 2013).

Though researchers are just beginning to understand the full impact of microplastics on human health, there’s already reason for concern. Some types of microplastic can disrupt and destabilize the lipid bilayers comprising cell membranes. Others increase oxidative stress, trigger apoptosis, and alter immune system function (Danopoulos E, et al. J Hazardous Materials, 2022).  

Possible Microbiome Effects

Plastic breakdown products might also be harmful to our gut microbial ecology, says Vanessa Stadlbauer-Köllner, MD, a clinical gastroenterologist in the Department of Gastroenterology & Hepatology at the Medical University of Graz, Austria.

“From animal studies it’s already known that microplastic causes changes in the gut microbiome. When you feed mice with microplastic they develop microbiome changes. And when you look at this microbiome it looks like that of somebody who is obese or has cancer, or has some other diseases like diabetes. You see a loss in diversity, an increase of potentially pathogenic species,” Dr.  Stadlbauer-Köllner told Holistic Primary Care.

“Could it be that microplastic in our environment is one of the factors that causes obesity and metabolic disorders?”

Public Health Implications

Given the ubitquity of plastics in our surroundings, exposure to MNPs begins practically at birth, and it increases as we age.

Dr. Marfella and his colleagues speculate that this could be one of the many factors that underlying the very well-established correlation between age, carotid stenosis, and cardiovascular disease in general.

They also point out that some people are much more likely to be breathing and ingesting MNPs than others. Certainly, anyone who works in manufacturing of plastics, or at other jobs that involve constant engagement with plastics will be at greater risk of MNP exposure.

Generally speaking, Blacks, Asians, Hispanics, Latinos, and low-income populations are exposed to higher levels of fine particulate air pollution than Whites and economically well-off people.

The Italian researchers hold that while there are not yet any epidemiological studies looking specifically at racial, ethnic, geographic or socioeconomic differences in MNP exposure, it is reasonable to extrapolate from patterns observed with other pollutants, that the aforementioned groups experience greater MNP exposure as well.

The biggest question prompted by the Marfella MNP study is, what to do about it?  This question applies at both the personal and public health levels. Plastics are everywhere in our environments. Production and use of plastics has not declined over the years. In fact, it has increased steadily since the 1950s. Global production of plastics doubled in the 20 year period from 2002 to 2022, from 200 million metric tons to 400 million metric tons.

China is now the biggest plastic producer, accounting for 32% of all plastic materials in 2022; the US contributes roughly 17%.

If MNPs are indeed an independent risk factor for cardiovascular disease, it is one that our species will be contending with for a long, long time.

Microbes to the Rescue?

A glimmer of hope in this otherwise dismal picture is coming from some very cutting edge microbiome research showing that certain bacteria, including a particular strain of Pseudomonas aeruginosa, are able to form biofilm “nets” that can trap and bind microplastics.

Building on work by Professors Song Lin Chua and James Kar-Hei Fang at the Hong Kong Polytechnic Institute, Dr. Stadlbauer-Köllner and her colleagues at the Medical University of Graz, are planning studies to look at bacterial strains that could potentially digest microplastics.

“There are some enzymes present in some bacteria that can digest certain kinds of plastics. And some of these bacteria belong to families that occur in the human gut microbiome,” she told Holistic Primary Care. “So, we will screen common gut commensals to see whether they have the genes to produce the enzymes that digest plastic. Then we will feed them with plastic and see if they can really degrade it.”

Though this is obviously a long way off from clinical application, it could very well turn out that it’ll be the microbes that spare us from our own environmental and physiological folly.

END

Fraudulent Research Floods Nutrition Field, Corroding Credibility

Good medical practice is based on trust.

Patients trust that practitioners are knowledgeable, and that they put their knowledge in service of their patients’ best interests. In turn, practitioners trust that clinical researchers run their studies honestly, and that the editors and peer-reviewers of the medical journals carefully scrutinize the papers they receive, sift out the garbage, and only publish studies that pass clinical, statistical, and ethical muster. 

Research is, in itself, a trust proposition. From the lead investigators who design trials, and the Institutional Review Boards (IRBs) that approve them, to the research assistants and post-doctoral fellows who crunch the data, and the authors who write and submit the papers for publication, there’s a thread of trust that depends on the right people doing the right things at each point along the path.

That’s how it ought to be in an ideal world. But the hard truth is, this is not an ideal world.

It’s an open secret that medical research fraud is rampant.

A recent article in The Guardian estimated that last year, there were more than 10,000 fraudulent papers retracted by journals across the sciences. That’s the highest number of retractions ever recorded. And this is likely just the surface layer of the problem.

Epidemic Proportions

Research fraud is widespread across many domains of healthcare, but it is especially problematic in the field of nutrition, says Alan Gaby, MD, a holistic physician who is author of the massive textbook, Nutritional Medicine.

Now in its third edition, Gaby’s book contains nearly 17,000 research citations and covering the use of herbs and nutraceuticals for more than 400 specific health conditions. Suffice to say, Dr. Gaby has probably read more clinical research papers on nutrition than anyone on the planet.

He contends that the problem of research fraud has reached epidemic proportions.

“Over the past 50 years, I’ve probably reviewed about 50,000 papers. And about 15 years ago, I became aware of some irregularities in a lot of the research. A growing number of papers left me wondering if the research had actually been done at all, or if the data were simply fabricated.”

Fraudulent research corrodes public trust; it misleads clinicians; and it skews metanalyses. Once marketers and sales people get hold of it, they easily turn it into dishonest and misleading product claims. At minimum, ordinary people get ripped off. At the extreme, people could get hurt.

Gaby says the number of suspicious—or at least highly questionable–papers has surged dramatically in recent years, in part due to the growth of open access publishing and the proliferation of small, poorly refereed open-access journals and websites, some of which are pay-for-play operations.  

But open-access is only part of the problem. Gaby says he’s seen numerous instances in which dubious nutrition studies have appeared in venerable, “high impact” (ie, widely-cited) conventional medical journals.

“Several hundred papers per year, in my view, raise questions about whether the research is legitimate.”

Gaby stressed that it is difficult—and time consuming—to prove definitively that a published paper is fraudulent. But there are an alarming number of studies that simply do not hold up to careful scrutiny. When this happens in respected peer-reviewed journals, as it sometimes does, it suggests that peer reviewers are failing to do their jobs, or that they’re turning a blind eye to shoddy work.  

He published his concerns in an excellent 2022 article in Integrative Medicine: A Clinician’s Journal, and in lectures and webinars.

The “Sato Saga”

Dr. Gaby is not the only physician ringing alarm bells. Several years ago, a team of researchers based in New Zealand called out two prominent Japanese investigators—Yoshihiro Sato and Jun Iwamoto—claiming that nearly 300 of their published papers in 78 medical journals, had major methodological flaws, ethical lapses, and signs of fabrication.

Sato, who died in 2017, and Iwamoto were both prominent professors at Japanese universities. Their work was primarily focused on bone metabolism, and they published many studies looking at the effects of Vitamin D, Vitamin K, and folate. They also studied prescription drugs like methylprednisolone, hormone replacement therapy, and valproic acid. Some of their research extended into fields like neurology and gastroenterology.

Studies by Sato and Iwamoto have appeared in some of the world’s top journals, including the Journal of the American Medical Association (JAMA), Neurology, and the Journal of Bone and Mineral Metabolism.

The saga began in 2006, when biochemist Alison Avenell, the Chair of Health Services Research at the University of Aberdeen, Scotland, was delving into the question of whether vitamin D could reduce bone fractures. While plumbing the literature, she came across two studies by Sato. One involved a cohort of stroke patients, and the other, patients with Parkinson’s.

Avenell noticed that in both studies, the patient populations had exactly the same mean body mass indexes. That, she thought, was statistically unlikely. She started digging more deeply, and the more she looked, the more anomalies she found: unreasonably large treatment effects, unusually large patient populations, plagiarized text, numbers that simply didn’t add up.

“Expressions of Concern”

Soon after, Avenell teamed up with Andrew Grey, Mark Bolland, and Greg Gamble of the University of Auckland, New Zealand. The team undertook an exhaustive review of 292 papers published by Sato alone or in partnership with Iwamoto.

In 2016, this intrepid team published an in-depth takedown of 33 studies by Sato, Iwamoto, or both. They notified 78 journals that most, if not all, of the nearly 300 papers published by these two researchers were flawed at best, fraudulent at worst.

The ensuing drama, well chronicled by the American Association for the Advancement of Science’s journal, Science, ultimately resulted in retractions of 121 studies, three corrections, and 12 “editorial expressions of concern”—that’s journal-speak for, “We question a study’s validity but don’t have a solid enough case to retract it.”

Not long before he died, Yoshihiro Sato admitted that he falsified research, and absolved Jun Iwamoto of any direct responsibility.

The so-called “Sato Affair” is one of the biggest legacies of medical research fraud in history. According to Retraction Watch, a website founded by former Medscape VP, Ivan Oransky and science writer Adam Marcus, that monitors retractions across a vast range of scientific disciplines, Sato and Iwamoto hold the 4^th and 6^th places for highest number of papers retracted worldwide.

Who’s number one? That dubious honor belongs to Joachim Boldt, a German anesthesiologist and ICU physician, who’s had a stunning 194 of his published papers retracted because of data fabrication and lack of ethics board approval.

Red Flags for Fraud Detection

With fraudulent research on the rise across the medical landscape, and peer review boards apparently faltering, practitioners need to sharpen their critical thinking skills when reading clinical studies. But one need not become a statistician.

“Several hundred papers per year, in my view, raise questions about whether the research is legitimate.”

–Alan Gaby, MD

Over the years, Dr. Gaby has identified ten red-flag warning signs that raise the index of suspicion about misconduct or outright fraud:

• Implausibly prolific research output by a single researcher: A good clinical researcher typically completes and publishes 3-4 large, randomized, double-blind, controlled trials in a period of 5 or 10 years, Gaby says. Yet, some researchers publish 10, 20, or even 30 papers in that time span. “Whenever you see implausibly large research output, it makes you wonder how could they have possibly done all of that research.”

• Implausibly large patient cohorts: Gaby says that over time, people who read a lot of studies develop a good sense of how many people could be reasonably enrolled in a given trial. This is based in part on the number of researchers and clinics involved, the size of those clinics, their catchment areas, the general prevalence of the disease in question, and the stringency of inclusion/exclusion criteria. In some nutrition studies, a lone researcher claims to have a trial population far larger than one could reasonably expect even in a multi-center study, let alone a trial at a single clinic.

• Unusually short recruitment time: Recruiting patients for legitimate clinical studies is not easy, nor is it swift. It takes a lot of outreach, effort, and resources. If a study claims to have recruited hundreds of people with a particular disorder in a 3-month period, and they all met strict inclusion criteria, you should be suspicious.

• Rapid submission & publication: Most studies disclose the time period for patient recruitment, and the duration of treatment lasted. From that, you can estimate the earliest possible date of completion. Gaby says he sometimes sees studies in the nutritional literature that were submitted for publication very soon after it would be possible to complete the trial, based on the schedule described in the text.

“In some cases, we’ve seen papers that were submitted before it was possible to have completed the trial. In many other cases, only a few weeks to a month after the trial could have been completed. That’s also implausible, because in a real study, it takes a very long time to analyze data, to write the paper, and then to submit it.”

• An RCT before there is preliminary evidence of efficacy: Real clinical trials are costly. Few funding sources are likely to underwrite that cost without some compelling preliminary evidence from case reports, open-label uncontrolled trials, or pilot studies showing that the intervention in question might be beneficial. Yet, in the nutrition and botanical literature, there are many alleged RCTs done without such preliminary evidence.

• Effect sizes larger than one would expect from nutrients: “If you read a lot of medical literature, you start to get a general idea of how effective nutrients are. Sometimes it’s dramatic, but most of the time it’s not. Usually, it’s a combination of nutrients producing a moderate effect,” says Gaby. Yet, “in many of the studies I’ve looked at, there were much larger effects…effect sizes you usually only get from drugs. So that raises eyebrows.”

• No funding source is listed, or the study is “self-funded”: This is particularly important when researchers describe their studies as RCTs. Real RCTs are very expensive. If nobody is funding it, one has to wonder how the study was possible. And if funding sources are not openly stated, one needs to wonder why.

• The trial design raises ethical issues: If a study involves patients with serious, advanced disease, and they’re randomized to either a nutrient or a placebo, there’s likely an ethical problem. That’s because clinical research is still in the domain of patient care, and doctors have a responsibility to treat people with the best available therapies. Whether natural medicine advocates like it or not, the “best available” treatments for serious diseases are usually prescription drugs. If researchers intentionally withhold a viable drug option in order to test a nutrient against a placebo, they’re treading on shaky ethical ground.

• Implausible patient characteristics: Pay close attention to the stated inclusion and exclusion criteria, especially the age range and baseline characteristics. Dr. Gaby says he sometimes sees papers that indicate a particular age range for inclusion, but the when he looks at the mean ages and the standard deviations in the results, it would be mathematically impossible that all participants actually met the stated age criteria.

• A large study—especially an RCT—authored by a grad student. Grad students are the unsung heroes of clinical research. While they certainly deserve credit for their efforts, the reality of academic hierarchies is that they are seldom lead investigators, especially on big trials. Yet in the nutrition literature, one will often see big studies authored by a grad student or junior researcher, sometimes as the sole investigator. While this is not a universally damning indicator, it should raise the index of suspicion a bit, especially if there are other red flags.

Countries of Origin

Dr. Gaby says there’s another important indicator of potential scientific fraud: geography.

“The most common country of origin, by far, for questionable papers, is Iran. To a lesser extent, Egypt and China. Then India, Pakistan, Japan, and Italy.”

Though a German holds first place for total retractions, and other Japanese researchers aside from Sato and Iwamoto also rank high on Retraction Watch, Iran is now the world’s leader in terms of the sheer volume of questionable papers flooding the literature, says Gaby.

“It’s gotten to the point that if something comes out of Iran, I’m inclined to not bother even reading it. Which is too bad, because probably some of the studies are legitimate. But my estimate is that at least three-quarters and probably more of the studies coming out from Iran these days, and to a lesser extent from Egypt, Japan, Italy, and others, raise serious concerns about whether the studies were actually done.”

Iran has an advanced healthcare system—a mix of public, private, and non-governmental non-profit payers. On some public health metrics, it ranks higher than the US. Roughly 90% of all Iranian citizens there have some form of healthcare insurance.

Unfortunately, the country also has a highly competitive market for well-paying, high-prestige jobs that require advanced degrees and scientific prominence. That, along with a totally unregulated cottage industry of for-hire study writers, is a major driver of fraudulent research from Iran.

“The most common country of origin, by far, for questionable papers, is Iran. To a lesser extent, Egypt and China. Then India, Pakistan, Japan, and Italy.”

–Alan Gaby, MD

The problem is not new. In 2016, Richard Stone the International News Editor for Science magazine authored an article called, “In Iran, a Shady Market for Papers Flourishes.” In it, he reveals a lucrative business centered on fabricating research and getting it placed in the international literature.

For the equivalent of around $600 (1.8M Iranian Tomans), scientific aspirants can commission a paper or thesis that ‘doesn’t need lab work.” An additional $400 increases the odds that the paper will be published “under your own name” in a “reputable” journal. That means, a journal published by an internationally recognized publisher like Springer or Elsevier.

“Paper Mills”

Stone says there are several thousand of these ‘paper mills’ throughout Iran, mostly centered around prominent academic institutions. He cites a prominent member of Iran’s Academy of Sciences who, in 2014, estimated that roughly 10% of all masters and PhD theses awarded in the country –amounting to about 5,000 theses per year—are based on research that the candidates never did.

This is completely legal. There are no laws in Iran—or other countries for that matter–against fabricating scientific data or publishing bogus research. Stone notes that in 2016, a group of Iranian scientists concerned about scientific integrity proposed a law to criminalize—at least partially—the selling of concocted science. It never saw the light of day.

In his review in Integrative Medicine, and in his lectures, Dr. Gaby draws attention to several Iranian researchers who published prolifically on nutritional topics, and whose work is very likely fraudulent.

Asemi’s Astonishing Output

Among them, Zatollah Asemi, a metabolic disease specialist at the Kashan University, who published more than 191 “RCTs” over his career, including 148 studies published between Jan 2016 and March 2019.

“That’s almost 50 papers per year,” says Gaby. “Just on face value, that level of productivity should raise a red flag.”

Further, Asemi’s output indicates that he was simultaneously running as many as five RCTs looking at five different treatments, concurrently. “That is unprecented. In my decades of reviewing scientific papers, I’ve never come across anyone as remotely prolific as this.”

Asemi’s numerous citations cover nutrients and herbs including quercetin, ginger, probiotics, magnesium, zinc, Vitamin D, berberine, and melatonin. He and his colleagues claim they’ve used these to treat an equally wide range of disorders including metabolic syndrome, diabetes, depression, leukemia, osteosarcoma, and polycystic ovary syndrome (PCOS).

Papers by Asemi and colleagues have found their way not only to obscure open-access journals, but into some well-reputed high-impact ones like the American Journal of Clinical Nutrition, the Canadian Journal of Diabetes, and the British Journal of Nutrition.

Gaby says the alarm bells about Asemi’s research are loud and numerous.

Beyond the implausibly prolific output, nearly all of his 191 trials show unequivocally positive, “statistically significant” outcomes for the interventions being tested. Often the effect sizes are large—larger than one usually sees in legit nutrient studies.

Further, Asemi’s trials often have implausible time lines. “At least 12 of his papers were submitted to journals before it was possible to have completed the trials. That’s easy to determine because he says exactly when he started them, and how long they lasted.”

For example, a 2018 study of magnesium and zinc for women with PCOS, published in the journal Biological Trace Elements Research, states that recruitment was from June to August 2017, and that the treatment period was 12 weeks. If recruitment ended on August 1 2017, the earliest that a 12-week trial could have been completed would be October 24 2017. Yet the journal received the paper on Sept 27 2017—weeks before the treatment protocols could be completed.

Another of Asemi’s studies—this one looking at the effect of multi-mineral plus vitamin D supplementation in women with gestational diabetes— claims to have recruited 60 women with this condition, who were between 24 and 28 weeks’ gestation, at a single clinic, within a 3 week period. Dr. Gaby says this is highly unlikely.

“I looked up some data to see if that was even possible. The region where this study was conducted (a city called Arak), has a population of about 500,000. And I looked up the prevalence of gestational diabetes, and the birth rates for this area. What I calculated was that during any given 3-week period, only about 36 women in the entire city would have had gestational diabetes between 24 and 28 weeks’ gestation. Yet Asemi claimed to have recruited 60 such women at just one clinic.”

Reluctance to Retract

Gaby shared his concerns about Asemi with the New Zealand team that ultimately took down Sato and Iwamoto. The group obtained a grant to undertake an exhaustive review of 172 studies by Asemi and colleagues. The result? A comprehensive 115-page dossier which the Auckland group sent to editors at 65 journals. It details the myriad inaccuracies, implausibilities, discrepancies, and ethical breaches spanning Asemi’s career.

Progress has been slow, but as of now 12 of Asemi’s papers have been retracted, and editors have issued 85 Expressions of Concern.

Gaby says there are dozens of other Iranian researchers whose work is just as questionable. There’s Reza Safarinejad, an internationally known urologist, whose main interest is male infertility. He’s published numerous studies on the impact of coenzyme Q10 (ubiquinol) on semen parameters, sperm function, and pregnancy rates. He’s also published on omega-3s, selenium, and N-acetyl cysteine for male fertility. According to Gaby, nearly all of Safarinejad’s studies are problematic.

He points to one in particular: a 2009 paper in the Journal of Urology looking at the effect of CoQ10 on sperm parameters and hormone levels in 212 infertile men.

Safarinejad is the only author of this paper, and claims to be the sole treating physician. Gaby holds that 212 is an implausibly large cohort for a stand-alone urology practice doing its own non-funded research (no funding source is listed). “A single investigator does not have the time or resources to conduct such a large trial by himself.”

The protocol was equally implausible: It claims that all 212 men visited the clinic 12 times over a period of 13 months, and gave two semen samples at baseline, and two samples within a 1-2 week period around each visit. Further, the semen was collected after 3 days of recommended abstinence.

Implausible Protocols

“That’s 24 semen samples per subject, with a total of at least 72 days of abstinence over a 13-month period. I don’t know anybody who would do that. If somebody is infertile and wants to have a pregnancy, he’s going to want to have intercourse and have a baby. The idea that anyone would sign up for this (protocol) is crazy,” says Gaby.

There are also big logistical questions, like the process for collecting the samples. “While half the 24 semen samples could potentially have been collected during the 12 clinic visits, the other half (12 samples) would have to be collected between visits. That is, at home. The subjects would have to deliver the samples to the clinic within 1 hour of ejaculation, because sperm cells start to die off after an hour. So, they would have to get to the clinic within one hour, on 12 different occasions. The paper claims 194 of the 212 men completed the trial and provided all the required 24 samples. That defies belief.”

Safarinejad claimed that he and a lab tech did all the semen analyses. Doing the math, that’s 4,650 sets of lab tests, all of which had to be done within hours of ejaculation. That’s a heavy workload even for someone not running a busy clinic.

Further, the study’s inclusion criteria states that men were eligible to participate only if they had “normal” fertile female partners “according to investigation.” That meant the women had undergone a complete medical history, physical exam, lab testing, and hysterosalpingogram.

“Doing this on 212 women would be very expensive and time-consuming. It is not something a urologist would do, so it would be done by a gynecologist. But the paper does not specify who conducted these fertility evaluations and who paid for them. And since Safarinejad is the sole author, and there’s no indication of funding source, it defies the imagination that 212 women would have had salpingograms just so their husbands could participate in a study.”

Dr. Gaby sent a letter to the editors of the Journal of Urology detailing his concerns. “They wrote back by email within 3 hours saying they were going to investigate this. It took about 6 months, but a couple months ago they issued an Expression of Concern about all 14 papers that Safarinejad had published in their journal.” It’s slow progress, but this is several steps in the right direction.

The examples cited above are but a few. Gaby says he’s identified many more problematic studies from Iran and from other countries. And keep in mind that the US is definitely not immune to bad research.

Corrosion of Trust

Fraudulent research corrodes public trust in science; it misleads clinicians; and it skews metanalyses and systematic reviews. Once marketers and sales people get hold of it, they easily turn dodgy data into dishonest and misleading product claims. At minimum, that means ordinary people get ripped off. At the extreme, people could get hurt.

There’s no lack of dubious research on pharmaceuticals, but the problem is especially damaging to the field of natural medicine which is continually fighting for credibility in the eyes of the broader medical community, the public, and the regulators. Fraudulent studies like those described in this article bolster the critics who want to paint the entire supplement industry as dishonest and maleficent.

As is easily seen from Dr. Gaby’s experience, and the New Zealand group’s efforts, medical journals are reluctant to retract studies once they’re published. People don’t like to admit they’re wrong, and retractions make journals—and their editors—look bad. Plus, there could be potential accusations of libel, even lawsuits.

Even if papers are retracted, their negative impact lingers, especially if they’d been in the literature for a long time, they appeared in high-impact journals, and they were included in metanalyses.

Despite his extensive experience exposing fraudulent research, Dr. Gaby stresses that most nutrition/supplement researchers are honest, and most studies are clean.

“Most nutrition research is believable, and the incidents of fraud do not change my observation that nutritional medicine is highly beneficial for prevention and treatment of a wide range of health conditions. But this is a stain on scientific integrity.”

END

Natural Alternatives to Ozempic

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Eczema: A Holistic Approach

Eczema is seldom life-threatening, but it can have profoundly detrimental impact on the people it affects. Clinicians who can bring a holistic, root-cause approach to this common condition can make a big difference in the lives of their patients.

“Roughly 20 million Americans have eczema. It’s a huge population. Patients are desperate for help, and very few practitioners are providing holistic, functional dermatology care,” says Julie Greenberg, ND, founder of the Center for Integrative & Naturopathic Dermatology, Los Angeles.

Severe eczema, aka atopic dermatitis, causes significant physical suffering, disrupts sleep, and often leads to social isolation and depression. Some patients find it difficult, if not impossible, to work. That means the disorder can cause long-term economic hardship.

“It’s not just a little rash. It can really impact lives,” said Greenberg in a webinar hosted by Integrative Practitioner. “These patients are motivated, they’re compliant, they really want to get better,” Dr. Greenberg said. One of her severe eczema patients once told her, “If you tell me to eat dirt, I’ll eat dirt.”

Dr. Greenberg, who is also a registered herbalist with the American Herbalists Guild (AHG), has years of experience treating severe skin disease exclusively with diet, lifestyle change, and botanical medicine. Through her Root Cause Dermatology training program she’s teaching other clinicians to do the same. The need for this, she says, is tremendous.

Boiling Over

The word eczema derives from the Greek “Ekzein”, meaning to “boil over.” The very name implies heat, inflammation. And that, says Greenberg, should be the central focus of treatment.

She stressed that chronic skin problems like eczema are rarely just skin problems. In nearly all cases, there are underlying systemic problems that warrant attention. “It is a disease of skin barrier dysfunction, but also a disease of deep systemic inflammation.”

Think of eczema as “leaky skin,” which is directly analogous and often concurrent with leaky gut.

While it is important to quell the obvious symptoms and give patients some measure of relief, it is equally important to identify and mitigate the drivers of inflammation. As with all chronic inflammatory diseases, the specific drivers vary from patient to patient.

Not Just Th2

To effectively treat eczema, you need to start with the pathophysiology says Dr. Greenberg.

The standard immunological view is that eczema is a Th2-mediated disorder. Th2 immune responses are typically triggered by helminths, fungi, and allergens, and mediated by cytokines like IL4, IL5, and IL13.

It is generally true that people with eczema do show Th2 predominance, and many of the drug therapies for eczema, including the injectable biologics, squelch the Th2 response. “Compared with psoriasis, it (eczema) is completely different. Psoriasis does not have a Th2 component.”

But Dr. Greenberg stressed that eczema is not always exclusively a Th2 disease. “It can have a Th1 or Th17 component as well.”

Th1 responses are typically driven by intracellular bacteria, viruses, and protozoa, while Th17 responses are usually driven by extracellular bacteria and fungi at mucocutaneous sites. Some people even show a Th22 pattern, suggestive of tissue inflammation.

In evaluating people with eczema, it’s important to take all these factors into consideration.

Immunological Endotypes

Greenberg cited a 2019 review by Tali Czarnowicki and colleagues that looked at immunological endotypes in diverse populations with atopic dermatitis.

They compared European-American, Asian-American, and African-American cohorts, and found that while all showed Th2 features, the Asian-Americans were more likely to show Th17 responses than European- or African-Americans.

There were also age-related differences: pediatric patients were more likely than adults to show Th17 responses. These are just a couple of the endotype patterns that Czarnowicki discovered. The point is, atopic dermatitis may not be as uniform as we previously thought. This suggests that treatments also need to be individualized and tailored to immunological endotype, rather than simply to lesion severity (Czarnowicki T, et al. J Allerg Clin Immunol. 2019)

“An attempt to define the patient’s endotype before treatment should be made to optimize therapeutic responses moving toward precision medicine based on the different clinical and molecular disease subsets,” writes Czarnowicki. “Although Th2 axis activation seems to be a universal trait across the AD spectrum, it still might be the case that other or additional cytokine targeting will be highly effective for a particular subset of patients who present a distinct endotype.”

The Role of Food Allergies

Dr. Greenberg called food allergies the “elephant in the room” in eczema. Though it is not accurate to say food allergies ‘cause’ the disease, they certainly can play a role in driving the process and triggering flares.

“It’s important to consider, but strictly focusing on food triggers is less likely to give you strong traction in adults with eczema. Food eliminations can help some people, but it’s not a cure-all.

But again, the impact of food allergies—which can be IgG-, IgA-, or IgE-mediated–varies widely between patients. Age is a factor in this: allergies play a much more prominent role in infants and young children than they do in adults with eczema.

According to Thomas Werfel and Kristine Breuer at the Hannover Medical University, Germany, well over 50% of children with atopic dermatitis experience exacerbations in association with particular foods (Werfel T, Breuer K. Curr Opin Allergy Clin Immunol. 2004).

But adolescents and adults are far less likely to experience food-associated flares. Dr. Greenberg estimated that two-thirds of all adult eczema patients do not show signs of allergy to food or environmental allergens. That’s partly because people tend to outgrow childhood allergies to milk, eggs, wheat, soy, and other common allergens. Further, by the time people reach their 20s and 30s, they’re usually aware of their problem foods, and they tend to avoid them.

“It’s important to consider, but strictly focusing on food triggers is less likely to give you strong traction in adults with eczema. Food eliminations can help some people, but it’s not a cure-all. Try it and see. But if food elimination is not working, not giving total clearance, don’t get stuck. You need to dig deeper.”

Dairy is No Friend

What’s the most common culprit food group? Dairy.

“When patients do experience food-related eczema flares, 75% are due to milk or dairy,” Dr. Greenberg said, adding that when taking a patient’s history, it is really important to ask about all forms of dairy, not just milk.

“If you ask about “milk,” patients will think you mean drinking glasses of milk. They’ll say “no.” But then later you’ll find out that they eat a lot of cheese. So, ask about anything that’s produced by a mammal mamma for a baby, and that includes sheep and goats too.”

Without restoring gut health, it is difficult if not impossible to maintain skin health.

Greenberg says she encourages all her eczema patients to eliminate dairy. They might not all be frankly allergic to it, but as a food category dairy is seldom doing them any good. “I’ve yet to meet an eczema patient for whom dairy is doing any favors. So, I just take it out.” Other common trigger foods are wheat/gluten, eggs, peanuts, and soy.

“Wheat is 50/50. Some patients are sensitive, some are not. Stool testing and organic acid testing will usually show it,” she said. Regarding eggs, the degree to which people experience flares is often “dose dependent.” Most can eat eggs occasionally without flaring, but eating them several times per week or more increases the risk of flares.  

For some patients, wine and especially red wine, can be problematic. “It’s high in histamines, and high in yeast. In patients with fungal overgrowth, you don’t want to give more yeast,” Dr. Greenberg said. Further, alcohol converts to sugar which fuels inflammation.

Does Eczema Cause Allergies?

We could also ask whether eczema causes food allergies, says Dr. Greenberg. “It’s a weird way to think about things, but we think that this is likely.”

Food sensitization problems are 6 times more common in kids who have eczema compared with those who do not, according to a study by Tamara Strugar and colleagues (Strugar TL, et al. J Drugs Dermatol. 2019). Generally speaking, the eczema develops first, then the food allergies and sensitivities. 

Any type of skin barrier disruption during infancy positively predicts the emergence of food allergies by age 2. Dr. Greenberg noted that kids who have eczema early in life are also much more likely to develop asthma than those without eczema.  

Based on a systematic review of 66 separate studies, Teresa Tsakok and colleagues at the St. John’s Institute of Dermatology, London, estimate that one-third of all children with early onset eczema go on to develop food allergies, asthma, or both, later in life (Tsakok T, et al. J All Clin Immunol. 2016). Researchers have described this as the “Atopic Triad.”

Leaky Skin, Leaky Gut

What are the connections? Think of eczema as “leaky skin,” which is directly analogous and often concurrent with leaky gut.

The skin is constantly in contact with the external world, exposed to a host of potentially noxious substances such as environmental toxins, pollen, food allergens, viruses, mites, animal dander, plant irritants, and the like. “They’re outside us. They shouldn’t get in. They shouldn’t reach the dendritic cells. And when the skin is healthy, they don’t get in and the immune system remains calm,” she explained.  

Eczematous skin is characterized by breaches in the epidermal barrier. Things that should be on the outside get down into deeper layers where they reach the dendritic cells, and this generates the various types of T-cell responses.

The same thing is happening in the gut. Dr. Greenberg noted that each time we swallow—a phenomenon that happens roughly 2,000 times per day—we are bringing the “outside” world inside the body.

A healthy, well-functioning digestive tract has multiple mechanisms—stomach acid, mucus production, microbiome factors, tight junctions between endothelial cells—for preventing noxious stimuli from entering into the bloodstream and the tissues.

“In a leaky gut, there’s a breach of the mucosal layer and the lumenal contents get in, which is very inflammatory, leading to further breakdown of the mucosal barrier. Things get into the bloodstream that do not belong there. Lipopolysaccharides get through 

and activate the dendritic cells, causing the release of IL6, TNF alpha, IL1-beta, which drives inflammation.”

Treat the Gut

Whether the initial barrier breakdown is in the skin or in the gut, the key to long-term resolution of eczema lies in careful assessment and treatment of the latter. Without restoring gut health, it is difficult if not impossible to maintain skin health.

“I test and treat the gut in all my eczema patients,” says Dr. Greenberg. “I run a stool (microbiome) test and an organic acid test on every single patient I see, right before the first visit. As a naturopath, I’m interested in their digestive function, so I look at markers for what’s going in, and what’s coming out. I look at how someone’s extracting and absorbing nutrients from what he or she is eating.”

She says she pays close attention to several key aspects of gut health, including:

• Oral and Nasopharyngeal Microbiome: Though the intestinal microbiome dominates research and popular discussions about probiotics, it is only one part of the overall picture. Many problems begin upstream, with the oral and nasopharyngeal microbiomes. Dr. Greenberg advises checking the oropharynx. Is there evidence of gingivitis? Chronic nasal or sinus infection? Has the patient had extensive dental work? Root canal therapies?  All of these factors may play contributing roles in the underlying inflammation.

• Stomach acid production: Many people with eczema are hypochlorhydric. They’re not producing enough stomach acid, which means that potentially problematic microbes that would normally be destroyed in a properly acidic stomach, are getting through to the intestines. The problem is amplified in those who carry Helicobacter pylori, and those on acid-blocking drugs.

• Evidence of dysbiosis: Eczema patients often show overgrowth of certain commensal organisms, an absence of beneficial bacteria, and/or the presence of pathogenic bugs.

Microbiome Factors

A healthy human intestinal tract will show robust populations of Faecalibacterium prauznitsii—an important producer of butyrate—and Akkermansia mucinophila—which eats old mucus and stimulates endothelial goblet cells to produce more mucus.

Eczema patients almost always show low levels of both. That means they’re usually deficient in butyrate, which is produced by F. prauznitsii as it ferments dietary fiber. Butyrate is the preferred fuel of enterocytes, and it also quells inflammation. The absence of A. mucinophilia means the gut is less able to repair and restore its protective mucus layer.

Many eczema patients also show relatively low levels of beneficial organisms such as Bifidobacteria and Bacteroidetes, but overgrowth of Staphylococcus aureus, various species of Streptococcus, Escherichia coli, and fungi like Candida albicans.

These microbiome changes are evident very early in life. Lotte Nylund and colleagues at the University of Turku, Finland, showed that infants with severe atopic dermatitis have far lower levels of butyrate-producing bacteria in their GI tracts than do healthy infants and those with mild AD (Nylund L, et al. Allergy. 2015).

Generally speaking, the severity of atopic disease is inversely correlated with GI microbial diversity, and with the presence of butyrate-producing organisms.

A Role for Probiotics

Given these relationships, it’s reasonable to think that probiotic supplementation could be helpful in treating eczema. Dr. Greenberg says they do have a role, but on their own, they are seldom going to result in complete resolution of skin symptoms, especially in severe eczema. 

“I use probiotics, but it’s definitely not the only the only thing,” she said.

Clinical studies are conflicting. The most comprehensive paper on this topic–a 2019 systematic review of 44 separate trials of probiotics in atopic patients–came to a split conclusion: 50% of the studies showed benefits from probiotics, but the other 50% showed no effect (Petersen E, et al. Acta Dermatol Venereol. 2019).

That stalemate is due in part to the extreme heterogeneity of the studies included in the review: probiotic strains, doses, and treatment durations varied widely from trial to trial.

Dr. Greenberg said some of her own patients have been getting good results from a relatively new probiotic product containing live Akkermansia mucinophilia. Made by Pendulum Health, this is the only product on the market providing the live form of this important organism.

But again, Akkermansia probiotics are not a cure-all. Greenberg said she often uses spore-based probiotics as well. And she insists that her patients get at least 35 grams of dietary fiber per day, either from food, supplements, or a combination of the two. “I make all my patients take a lot of fiber. Most people really lack it in their diets.”

Tackling Candida

Candida is a big culprit in people with eczema.

GI overgrowth of candida shows a statistically significant correlation with IgE antibodies in atopic dermatitis patients (Savolainen J, et al. Clin & Experimental Allergy. 1993). The authors of this study noted that “Severe phases of AD in colonized patients are associated with IgE synthesis against C. albicans.”

When AD patients who do have IgE antibodies to Candida are treated with antifungals, the skin symptoms improve. This was shown 25 years ago, in a study by a team of dermatologists at Hiroshima University School of Medicine in Japan (Morita E, et al. J Dermatol. 1999).

“I find this 100 percent,” said Dr. Greenberg, referring to her own experience treating Candida in people with eczema.

Keep in mind that in addition to triggering a shift from Th1 to Th2 immunological patterns, the presence of fungi like Candida at mucocutaneous sites will also drive Th17 reactions. Many people with leaky gut will show Th17 reactions, and these are associated with autoimmune conditions. It’s important to keep this in mind.

Candida overgrowth is very common among people with eczema. “Get the Candida down, and the skin gets a lot better,” says Dr. Greenberg. She stressed that she treats fungal infections via dietary changes and herbal antifungals such as Rosemary (Salvia Rosmarinus), Pau d’arco aka Lapacho (Handroanthus impetignosus), and Uva Ursi (Arctostaphylos uva-ursi).

H. Pylori: A Hidden Culprit

Be on the lookout for Helicobacter pylori in your eczema patients, says Dr. Greenberg. 

Roughly half of all people carry H. pylori, and for many, it seems to cause no harm. This has led some researchers to view it as a benign commensal.  But for some people, this bug is highly problematic. It’s association with peptic ulcers, gastritis, and gastric cancer are well-known. Fewer people are aware that it is also linked to skin diseases like rosacea, chronic urticaria, eczema, severe acne, and alopecia areata. 

H. pylori can produce lipopolysaccharides and endotoxins, as well as biofilms, all of which can be problematic, especially in people who already have compromised mucosal barriers and systemic inflammation.

It also produces urease and other substances which create a buffer against stomach acid. This allows the organism to live in a very low-pH environment that normally would be utterly hostile for bacteria. In other words, it diminishes one of the body’s primary defenses against noxious stimuli from the outside world. The neutralization of stomach acid also leads to suboptimal digestion, which has downstream consequences.

“Stomach acid signals to the pancreas and gall bladder to produce bile and enzymes. A deficit of stomach acid leads to suboptimal production of enough bile, pancreatic enzymes,” Dr. Greenberg explained. “That’s not good for us.”

This acid-mitigating effect ensures H. pylori’s own survival, and it also enables potentially problematic protozoans like Giardia and Entamoeba to survive the stomach and enter the intestines.

Protozoans are common findings in stool analyses of people with eczema, and these patients almost always have H. pylori.

Are the protozoans always pathogenic? No, but Dr. Greenberg says she errs on the side of treating them as such. Her go-to botanicals for eliminating protozoans are Artemisia and Black Walnut (Juglans nigra). Likewise, she considers H. pylori to be an etiologic factor in eczema, and treats it accordingly, even if the patients do not have peptic ulcers or gastritis. Her preferred herbs for mitigating H. pylori are: Mastic gum, deglycyrrhizinated licorice (DGL), and black cumin (Nigella sativa).

The Ear Infection Connection

There is a strong connection between chronic ear infections and eczema. Dr. Greenberg noted that most children with eczema also have frequent ear infections. And if you ask, you’ll find that many adults with eczema have histories of chronic ear infections in childhood.  

The reasons for the association might not be obvious. But embryologically, it makes sense. The bones of the middle ear, and the eustachian tubes develop from the first and third pharyngeal arches which are the developmental foundation of the head and neck, including the pharynx. The eustachian tubes themselves open into the nasopharynx.

This means there’s a fundamental anatomical connection between the ears, the digestive, and the respiratory tracts. We think of them as separate systems, but actually, they are interconnected.

In a recent review paper, Amy S. Graham and colleagues at the Neuroscience Institute, University of Cape Town, South Africa, explored these connections in detail, coining the term “Auditory-Gut-Brain Axis.” They suggest that changes in the gut microbiome, chronic inflammation, and disorders of the ear and of auditory processing, may all be related (Graham AS, et al. Front Neurosci. 2023).

On the patient care level, Dr. Greenberg reported that she’s had a number of eczema patients who experienced complete clearing or at least significant improvement of ear infections after eliminating dairy and wheat as part of a lifestyle program to mitigate the eczema. “I started to advise my ear infection patients to cut out wheat and dairy, even if they don’t have eczema. Many have gotten better.”

Assessing Eczema Patients

In addition to a thorough history and physical exam, Dr. Greenberg’s initial assessment depends on two cornerstone tests: the GI-MAP (Microbial Assay Plus), a PCR-based test to detect the presence of various bacteria, fungi, viruses, worms, and protozoa in fecal samples; and an Organic Acid Test, to assess overall nutrition status, metabolic function, detoxification capacity, and neurotransmitter status.

“Every patient has to do the GI-MAP and the OAT before the first visit. I use these as a baseline. It’s immensely helpful. Depending on the clinical history, and initial evaluation, I might order other tests as well.”  

Other potentially useful tests include the DUTCH tests (Dried Urine Test for Comprehensive Hormones); Mold and mycotoxin tests; Hydrogen or methane breath testing for small intestinal bacterial overgrowth (SIBO); Food allergen tests; and specific tests to assess intestinal permeability.

“I use the labs as a roadmap. I know where we’re starting: severe eczema. And I know where we want to go: clear skin. The findings from the labs give clues on where to focus treatment-wise.”

Individualizing Treatment

Given the range of immunological endotypes, microbiome factors, and potential food and environmental triggers that can contribute to the pathogenesis of eczema, an effective treatment program must necessarily be individualized, says Dr. Greenberg. She adds that resolution of chronic eczema takes time, and that she typically shifts the focus of treatment every 2-3 months.

“These patients are motivated, they’re compliant, they really want to get better”

The fundamental goals of treatment are to quell systemic inflammation, eliminate inflammatory triggers, eliminate pathogens, restore a healthy gut, oropharyngeal, and skin microbiomes, and repair damaged skin and gut mucosa. 

She stressed that as a naturopathic physician, she does not use prescription drugs, but is able to achieve excellent results with lifestyle modification, dietary changes, food trigger eliminations, herbal antimicrobials, and probiotics.

“You have to go deep. It’s far beyond prescribing tubes of steroids or Th2 response inhibitor drugs. That’s all just system suppression. You push down the Th2 response, you push down the inflammation. But you’re not really finding and treating the root causes. You can’t just treat from the outside in, you have to also work from the outside in.”

She added that the general approach she takes with eczema patients will often work well for those who have psoriasis and other chronic skin disorders.

END

IBS & Osteoporosis – The BMP Connection

Irritable Bowel Syndrome (IBS) and Osteoporosis are two of the most common conditions that integrative practitioners see among their patients. These disorders are actually related.

The common factor? Bone Morphogenic Proteins (BMPs)—a group of cytokines that play important roles in bone and joint homeostasis as well as in GI mucosal integrity.

In this free webinar, Cynthia Worden, DO, will explore the connections between IBS and Osteoporosis, and share new insights into the dual role of Bone Morphogenic Proteins in supporting patients with GI and bone health issues.

She’ll also describe her clinical experience with Ostinol®–the only BMP-complex available for oral supplementation.

During this webinar, you’ll learn about: 

• The epidemiological relationship between IBS and Osteoporosis—and the rising rates of both conditions
• The discovery of BMPs, their structure, and their function within Demineralized Bone Matrix
• Mechanisms of action and observed clinical impact of BMPs
• The practical benefits of BMPs in supporting patients with IBS and Osteoporosis
• Case studies & clinical experience with Cyplexinol® Musculoskeletal Regenerative Nutrition

SPONSORED BY Regenerative Tissue Sciences, the professional sales division of ZyCal Bioceuticals Healthcare Co., Inc.

Cynthia Worden, DO, MSHPE, IFMCP earned her medical degree at Western University of Health Sciences in Pomona, CA in 2004. She also completed a teaching fellowship in Osteopathic Manipulation, a Master’s in Health Professions Education, and a Doctorate in Osteopathy.  Dr. Worden completed her Internship and Osteopathic Family Medicine residency training at Downey Regional Medical Center.

Following her training, she practiced Integrative Family Medicine at Creekside Family Practice in Portland, OR, for 10 years.  After discovering functional medicine, Dr. Worden realized it held many of the answers to her patient’s chronic medical conditions. She became a Certified Practitioner with the Institute for Functional Medicine (IFMCP) in 2016, after which she founded Bloom Functional Medicine in 2018.

Like many who practice functional medicine, Dr. Worden has faced her own health issues: Hashimoto’s and Crohn’s disease. Consequently, she has first-hand knowledge of how these conditions affect overall health and well-being. In her free time, she loves to spend time with her family and friends, and to continue her learning. She loves to cook, read, kayak, ski, hike, and travel.

Viroid Obelisks: The Microbiome’s Microbiome?

Just when you thought the microbiome couldn’t get any weirder, investigators at Stanford University have discovered a whole new dimension in the microbial universe: a category of distinct, self-replicating RNA sequences in and among bacteria of the human gut and oral microbiomes.

Named “Obelisks” owing to their circular rod-like structures, these peculiar bits of genetic information are unlike any genomic sequences in the known viral, bacterial, fungal, or animal worlds.

In discovering Obelisks, Nobel prize-winning geneticist Andrew Fire and his team believe they’ve opened an entirely new frontier in microbiology.

“Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents,” they write in their newly published article on bioRxiv.com, the Cold Spring Harbor Laboratory’s preprint server platform.

A New Frontier

So far, Fire and his colleagues have identified almost 30,000 distinct Obelisks, by applying a bioinformatics tool called VNom (Viroid Nominator) to databases containing 5.4 million genome sequence datasets.

Obelisks are diverse in structure, but they share several common features. They’re all circular RNA strands of no more than 1kb in length. That’s tiny even by the miniscule standards of molecular biology. They form predictable rod-like secondary structures. And they contain open reading frames that code for unique, previously unknown protein-like entities that the Stanford group has named “Oblins.”

In analyzing microbiome data sets representing the oral and gut microbiomes of 472 healthy human donors, they found that nearly 10% of these individuals carried one or more Obelisks among their commensal bacteria. These curious RNA sequences were more prevalent in oral versus gut microbiome samples (53% versus 6.6%), which suggests that the oral flora may be a reservoir for Obelisks in humans.

Streptococcus sanguinis, a facultative anaerobe that is part of the normal oral flora, is the first bacterium within the human microbiome that the Stanford team has identified as a definite host for Obelisks. The specific Obelisk subtype that Fire and colleagues discovered inside S. sanguinis, is able to replicate, and to produce a certain type of Oblin within the Streptococcal cells.

“Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents.”

–Andrew Fire, Professor of Molecular and Genetic Medicine, Stanford University

This, they say, is clear evidence that Obelisks can and do live—if such entities can be considered living–within bacterial cells. Though other bacterial hosts for Obelisks have not yet been identified, Fire says “it is reasonable to assume that at least a fraction (of the Obelisks) may be present in bacteria.”

Obelisks are Everywhere

Inside or outside of bacterial host cells, Obelisks seem to be everywhere. The Stanford group has detected them, at varying prevalence levels, in metatranscriptomes from people living in the US, Canada, Brasil, China, India, Russia, and Australia, as well as several countries in Europe and Africa. They’ve also found them in non-human mammals, fish, birds, arthropods, even in soil and sediment. Wherever there is life of any sort, there appear to be Obelisks.

Are Obelisks friendly? Fearsome? Both? At this point, nobody knows.

They do share some structural traits with viroids—the small, non-encapsulated DNA or RNA strands typically found in plants, and which are sometimes pathogenic. The potato spindle tuber viroid (PSTVd), and the citrus exocortis viroid (CEVd) are two common examples of pathogenic plant viroids.

Like viroids, Obelisks are very small circular RNA sequences that lack protein coats. This absence of a protective protein capsule is the key feature that distinguishes both viroids and Obelisks from true viruses.

So far, none of the 29,959 Obelisks discovered by Fire and his team appear to cause harm to the bacteria among which they’re found, or to their human meta-hosts. And there’s not yet enough information about them to determine whether they are helpful.

Are Obelisks friendly? Fearsome? Both? At this point, nobody knows.

It is clear that Obelisk RNA sequences can be transcribed into protein-like structures, but the function of these so-called Oblins is an open question.

The Stanford researchers have found only one such Oblin that has an identifiable function: a self-cleaving ribozyme similar to the hammerhead type-III ribozymes. Hammerhead ribozymes are RNA catalytic cleavage sequences found in genomes throughout the bacterial, viral, and eukaryotic realms. 

Beyond that, almost everything else about Obelisks and Oblins is a mystery at this point.

A Cornucopia of Questions

Lead investigator Andrew Fire is no stranger to the frontiers of knowledge. In 2006, he and his colleague Craig Mello won a Nobel Prize in Physiology or Medicine for their discovery of RNA interference (RNAi)—a mechanism that regulates gene expression. At the time, their elucidation of RNAi revolutionized scientific understanding of how genomes self-regulate. Their work underscored the ways in which tiny bits of double-stranded RNA can turn off gene transcription.

In the years since, Fire and his group have continued to delve into the mysteries of RNA, and they’ve developed sophisticated methods for detecting previously unidentified RNA sequences. It is this work which led to the discovery of Obelisks.

In his new paper, which has yet to be peer-reviewed, Fire acknowledges that the discovery of RNA Obelisks raises a cornucopia of interesting questions: How do Obelisks replicate? How do they move from extra- to intracellular environments? How many different Obelisk subtypes are there and what do they code for? What types of bacteria are most or least amenable to hosting Obelisks? Do the Oblins transcribed from the Obelisks have any important biological functions?

In microbiome data sets representing the oral and gut microbiomes of 472 healthy human donors, nearly 10% of these individuals carried one or more Obelisks among their commensal bacteria.

There are also big questions about how Obelisks affect the microflora in and around which they dwell, and by extension, the higher organisms that host these commensal microbes.

“Are Obelisks plasmid-like in that they can co-exist, and in some cases, contribute to host adaptability and fitness?” Fire asks. “Are they largely a deleterious or beneficial element to harbour? And what impact, if any, does harbouring an Obelisk have on ‘meta’-host physiology? Is Obelisk positivity predictive of human health states?”

Again, the answer to all of these questions is: We don’t yet know.

A New ‘ome?

It is notable that Obelisk prevalence, like microbiome composition, varies by anatomic site: the presence of Obelisks is much higher in the oral versus the intestinal microbiome.

Obelisks may—at least in part—be “colonists” within specific types of bacteria, in a similar way that various commensal bacteria have specific preferences for colonizing particular organ systems.

By way of rough analogy, the Obelisks might be something akin to the microbiome’s microbiome.

Dr. Fire speculates that if that proves to be the situation, then “donor-specific factors such as diet or lifestyles therefore likely play a role in Obelisk (re-)colonisation and retention.”

He adds that further study of S. sanguinis will be an important line of research in clarifying the relationship between these newly discovered RNA agents, the various microbiomes, and human physiology.

“Study of the implied S. sanguinis-Obelisk relationship might begin to reveal the relevance of Obelisks to the natural oral niche and potentially to human health, as well as offer a tractable model system to study Obelisk molecular biology.”

On the Threshold of Life

Researchers now know vastly more about the interrelationship between commensal microbes and human physiology than they did 20 years ago. But the Stanford group’s discovery of viroid Obelisks underscores just how much there is yet to discover about the invisible worlds that shape our existence.

This is especially true of viruses and related entities. In fact, the virome may be even more complex, influential, and downright weird than the bacterial microbiome.

According to an article by UC San Diego’s David Pride, and Rockefeller University’s Chandrabali Ghose, there are an estimated 380 trillion viruses inside the average human body. That’s ten times the already staggering number of bacteria in the typical human microbiome.

The overwhelming majority of viruses and viroid particles appear to be harmless. Those that are harmful are usually pathogenic to specific species. There are very few examples of viruses that cause disease throughout the animal kingdom.

Some viruses may actually be helpful. Researchers now know that genes from viruses known as HERVs (human endogenous retroviruses) account for up to 9% of the total human genome.

Obelisks appear to dwell at the threshold between entropy and order, between the realm of living things and the vast universe of inanimate matter. Their discovery is a brilliant burst of light into a domain that researchers have termed “viral dark matter.”

So far, early responses to the discovery from microbiologists and molecular biologists have been enthusiastic and positive. Beatriz Navarro, a plant viroid expert based at the Institute for Sustainable Plant Protection in Bari, Italy, praised it as “impressive,” in an interview published in New Scientist.

“Really wild and cool discovery for virus nerds,” gushed Steven Salzberg, a biostatistician at Johns Hopkins University.

Computational biologist Simon Roux, at the DOE Joint Genome Institute at Lawrence Berkeley National Laboratory, told the journal Science that he is “really impressed by the approach” that Fire and colleagues took in their work.

Roux is among a group of scientists who surmised that viroids—or similar non-encapsulated entities—might exist beyond the botanical world, inside commensal bacteria. The Stanford discoveries give credence to that hypothesis.

He added that the discovery of Obelisks begs the important question of whether true viruses evolved out of things like Obelisks and viroids, or rather the other way around–that Obelisks and viroids are the result of de-evolution of viruses or other more complex forms of life.

It will probably be years before we know if Obelisks have a role in human health or illness. But it is clear that their discovery is the first step in what will likely be a long and exciting scientific odyssey.

END

For Disease Risk Reduction, Broc Rocks!

Imagine if there were a drug that could reduce risk of cancer and cardiovascular disease by roughly 40%, without any adverse effects. Even better, people would only need to take it 2 or 3 times per week to obtain these preventive benefits.

It turns out there is such a thing. It’s called broccoli.

People who regularly eat broccoli once or twice weekly can reduce their all-cause mortality by an impressive 32% to 43%, according to a new analysis of data from more than 5,500 US adults.

Frequent broccoli consumption had a particularly strong impact on deaths from cancer and cardiovascular disease, according to a collaborative research team based at the Jilin University Hospital, Changchun, and the Beijing Shijitan Hospital, Capital Medical University, Beijing.

“Consuming broccoli 1–2 times per week for males and 3 or more times per week for females could significantly reduce all-cause mortality risk,” report Xiangliang Liu and co-authors.  They suggest that, to a point, broccoli consumption may confer something like a “dose-response” effect on death rates from common diseases: the more frequently someone eats this healthful crucifer, the greater the mortality reduction.

They base that conclusion on a detailed study of data from 12,486 Americans in the NHANES (National Health and Nutrition Examination Survey) 2003-2006 cohort. The NHANES project uses an extensive Food Frequency Questionnaire (FFQ) to gather detailed dietary information from participants. The FFQ includes two questions specifically about broccoli: “Have you ever consumed broccoli?” and “How frequently do you consume broccoli?”

A total of 5,556 participants in the 2003-2006 NHANES cohort (2,743 males and 2,813 females) provided complete responses to these broccoli questions. All were over 20 years of age; 30% were over age 65.

Based on those responses, Dr. Liu and colleagues divided the cohort into four categories: never consumers (N=739), infrequent consumers who ate broccoli “less than once a week” (N=3,181), occasional consumers, defined as “1 to 2 times per week but less than 3 times per week” (N=1,216), and regular consumers, meaning those who ate broccoli “3 or more times per week” (N=420).

Impact on CVD & Cancer

During the 10-year follow-up period, which ended December 31, 2019, there were a total of 1,405 deaths from all causes among the 5,556 subjects (25.3%). Cardiovascular disease caused 504 deaths (35.9%), and cancer accounted for 292 deaths (20.7%). There were 107 deaths (7.6%) attributed to pulmonary/respiratory diseases, with the remainder attributed to accidents, renal disorders, diabetes, or “miscellaneous causes.”

After applying three different statistical models to control for a wide range of other variables associated with increased mortality, such as age, gender, race, education level, socioeconomic status, body mass index (BMI), smoking, and alcohol consumption, Liu and colleagues saw a clear signal: broccoli intake is inversely correlated with mortality.

In the statistical model with the strictest controls on potentially confounding variables, they found that compared with people who said they never ate broccoli, those who ate it occasionally (less than once weekly but several times per month) had an all-cause mortality hazard ratio of 0.7—a 30% risk reduction. For those who ate broccoli 1-2 times per week, the hazard ratio dropped to 0.58. That’s a 42% risk reduction.

But among the broccoli-lovers, who reported eating it 3 or more times per week, the hazard ratio was 0.72 compared with never-eaters, a finding that suggests the risk-reductive effect plateaus at a certain intake frequency, beyond which there’s no further gain.

Looking specifically at cardiovascular risk, they found a similar pattern: compared with never-eaters, those who ate broccoli occasionally had a 21% risk reduction, and those who ate it 1-2 times weekly had a 38% risk reduction.

The cancer data also showed this pattern: those who ate broccoli occasionally had a 30% lower risk of cancer-related mortality than the never-eaters. For those who ate it 1-2 times per week, the hazard ratio was reduced by 41%. Among the most frequent broccoli eaters, the risk was also reduced by 41% compared with non-eaters, again suggesting that the protective effect reaches a plateau (Liu X, et al. Front Nutr. 2008).

Gender Differences

Dr. Liu and his colleagues saw a distinct gender-based difference in the pattern of risk-reduction: Males seem to obtain a greater benefit at lower consumption frequency than females. The latter need to eat broccoli at least 3 times per week to gain the all-cause mortality reduction that men get from once or twice weekly intake.

The reasons for this difference are not entirely clear, but the authors do offer a couple of speculations about it:

“On the one hand, the intake of fruits and vegetables is inherently higher in females’ diets, so they may need to eat broccoli more frequently to produce significant health effects. On the other hand, increased estrogen levels can promote the expression of glutathione peroxidase, enhancing the body’s antioxidant capacity, which may make females require higher amounts of antioxidant nutrients in broccoli.”

Putting it simply, women tend to have higher antioxidant intake along with higher inherent antioxidant capacity than men do. Therefore, to see an impact on mortality, women would need to eat substantially more broccoli than men.

A True Superfood

The risk reductions reported by Liu and colleagues are impressive in their magnitude, but they should not be entirely surprising: broccoli is an extremely fiber-rich and nutrient-dense vegetable. The authors cite a number of key nutrients within broccoli which likely play a role in its risk-mitigating effects:

• High levels of direct antioxidants such as vitamin C, carotenoids, and anthocyanins, that can quench oxygen-free radicals and mitigate oxidative stress.
• Sulfur-containing phytochemicals like glucosinolate, which inhibit the production and release of inflammatory mediators, and which also stimulate production of antioxidant enzymes.
• Sulforaphane, which promotes insulin signal transduction in the liver and in skeletal muscle, thus improving insulin sensitivity and regulating blood glucose.
• High levels of vitamin K1, a fat-soluble vitamin that promotes production of clotting factors while inhibiting the synthesis and secretion of cholesterol from the liver.
• A wealth of flavonoids that can scavenge free radicals and accelerate cholesterol breakdown.
• High levels of water-soluble mucilaginous fiber, that can prolong gastrointestinal transit time and improve digestion, bind bile acids, and slow the absorption of carbohydrates, thereby preventing post-prandial glucose and insulin surges.
• Rich in minerals, especially magnesium, which can reduce cholesterol absorption.

“Adequate intake of broccoli helps maintain the functionality of pancreatic beta cells, preventing insufficient insulin secretion due to pancreatic cell injury and thus stabilizing blood glucose regulation,” the authors stated. “By regulating glucose and lipid metabolism and enhancing insulin sensitivity, broccoli can reduce the risks of metabolic syndrome, type 2 diabetes, and cardiovascular diseases.”

To some degree, Dr. Liu’s team was able to quantify the anti-inflammatory effects of broccoli consumption. Using blood samples obtained from the NHANES participants, they measured monocyte, lymphocyte, platelet, and neutrophil counts, and found a clear reduction in the neutrophil-to-lymphocyte ratio—a key cellular marker of inflammation—associated with increased broccoli intake.

“Substantial evidence indicates that chronic inflammation and oxidative stress play important roles in the pathogenesis of various chronic diseases, including cancers, cardiovascular diseases, and type 2 diabetes,” Liu and colleagues state in their report. “Therefore, the abundant anti-inflammatory and antioxidant components in broccoli may be important nutritional mechanisms for its beneficial effects against chronic diseases.”

Who’s Eating Broccoli?

In their analysis, the Beijing researchers found several interesting demographic disparities in frequency of broccoli consumption within the NHANES cohort: women tended to eat it much more frequently than men, and non-Hispanic whites ate it more often than other racial/ethnic groups.

There was also a surprising relationship between socioeconomic status (as indicated by poverty income ratio) and broccoli consumption: those in the middle range tended to eat more broccoli than those at the low and the high ends of the socioeconomic spectrum.

Like any epidemiological study based on diet questionnaires and self-reporting, this one too has methodological limitations. The authors acknowledge the possibility of recall bias and participant subjectivity, which should be taken into consideration when drawing conclusions about the data.

Even with those limitations in mind, it is clear that regular broccoli consumption has a significant impact on reducing death rates from cardiometabolic and neoplastic disease. Pharmaceutical executives dream of finding novel drugs that can knock 30% or 40% off the mortality rates from common diseases.

Quantifying “Food as Medicine”

By studying the relationship between consumption frequency and disease-associated mortality rates, Liu and colleagues are, in a sense, attempting to quantify the concept of “food as medicine.”

They note that while there have been many studies of broccoli and other cruciferous vegetables over the decades, and most show positive health impacts. But few prospective studies have looked specifically at the effects of low, moderate, and high intake levels.

In the introduction to the study, they point out that “the available data do not provide specific recommendations for broccoli consumption frequency. Therefore, it is of great significance to use large sample prospective study results to analyze the dose–response relationship between broccoli intake frequency and all-cause and cause-specific mortality, which can provide guidance for dietary adjustment in different populations, especially dietary interventions for patients with chronic diseases.”

Though further research is needed, not just on broccoli, but on other ‘healthy’ vegetables, Liu’s study makes a strong case that men who eat broccoli once or twice weekly, and women who eat it three or more times per week, are doing themselves a great favor.

END

The Lancet Explores Medicine’s Most Shameful Chapter

How did the most sophisticated and scientifically advanced medical system of its time become an agency of systematic state-sanctioned mass murder?

It’s a question that haunts anyone who looks at the history of medicine during Germany’s Third Reich. And it is the subject of a comprehensive new report from The Lancet.

Issued in early November, to coincide with the 85^th anniversary of Kristallnacht—the violent pogroms generally considered to be the start of the Nazi effort to exterminate the Jews —The Lancet’s report is the most thorough exploration of this troubling subject to date. 

Richard Horton, MD,  The Lancet‘s Editor-in-Chief, convened the 20-member Commission on Medicine, Nazism, and the Holocaust to develop “a reliable, up-to-date compendium of medicine’s and medical professionals’ roles in the development and implementation of the Nazi regime’s antisemitic, racist, and eugenic agenda, which culminated in a series of atrocities and, ultimately, the Holocaust.”

Co-chaired by medical historians Herwig Czech, of the Medical University of Vienna, and Shmuel P. Ries, MD, of the Hebrew University Hadassah Medical School, Jerusalem, the commission included physicians, historians, and medical ethicists from Austria, Spain, Germany, Israel, Czech Republic, Poland, and the United States.

“Medical crimes committed in the Nazi era are the best-documented historical example of medical involvement in transgressions against vulnerable individuals and groups. What happened under the Nazi regime has far-ranging implications for the health professions today, and virtually every debate about health professional ethics can gain from an understanding of this shameful history,” the authors write in their introduction.

The Lancet report emerges at a time when many people glibly throw around terms like “Nazi” and “genocide,” and “concentration camps” in political discourse to support a range of often opposing causes and positions. Deliberately inflammatory use of such words is clearly displayed on both sides of the discourse about the current Israel-Hamas conflict.

Just 3 years ago, the same sort of button-pushing language arose during the Covid pandemic, when some opponents of vaccine mandates invoked the specter of Nazi medical experiments to make their case. It has come up repeatedly in debates about healthcare reform, where opponents of national healthcare decry “government death panels.”

The Lancet’s report also comes at a time of widespread Holocaust denial, when the ranks of those who actually experienced the horrors of World War II are growing thin, and the global geopolitical order is increasingly unstable.

In light of all of this, it behooves us all to learn what actually happened in Germany and surrounding countries from 1931 to 1945.

Exclusion From Healthcare

The atrocities of the Holocaust were the culmination of longstanding cultural and political movements in which “science, medicine, and public health were used to justify and implement persecutory policies and eventually state-sanctioned mass murder and genocide.” The Lancet committee defines the latter term as “the targeted murder of specific religious, racially defined, national, or ethnic groups.”

The report traces the origins of these movements from their roots in late 19^th Century European “race science,” through their dissemination during the tumultuous Weimar-era of German history, and ultimately through their operationalization as national policy after 1933, when Hitler took power as Germany’s chancellor.

The Weimar period was a time of great political and economic strife in Germany, and in much of Europe. It was also a time of rapid scientific and technological advances, as well as social change. During that period, the ranks of German medicine included a growing number of Jews, women, and non-German immigrants. The Lancet report cites a 1933 German census showing that while Jews comprised roughly 1% of the nation’s population, they represented roughly 10% of its doctors. Not everyone was happy about that.

One of the new Reich’s first formally racist anti-Jewish policies was a general boycott of Jewish-owned businesses–a call that explicitly mentioned Jewish physicians’ practices.

This was quickly followed by the 1933 Law for the Restoration of the Professional Civil Service, which forbade Jews from holding positions in the civil service, including the public health service, and at universities, which included medical schools. The Lancet committee states that this led to the immediate dismissal of nearly 20% of all people working in academia, 80% because they were Jews and 20% because they were deemed enemies of the Nazi regime. 

Further legislation in April and June of 1933, explicitly excluded Jews and other “political opponents” from receiving payments from the nation’s health insurance system.  By 1938, the Reich stripped all Jewish physicians of their medical licenses, made it illegal for them to call themselves doctors, and forbade them from treating non-Jewish, ethnically German patients.

From Genetics to Genocide

Though extermination of Jews was always part of Hitler’s plan, the industrial scale mass murder that we’ve come to know as the Holocaust did not begin with Jews, or for that matter, with the Roma, Sinti, homosexuals, or political prisoners all of whom ultimately became victims of the Nazis’ agenda. Rather it emerged out of the Reich’s eugenics program, and it began with forced sterilization of people with physical disabilities and psychological disorders.

At the core of the Nazi ideology was the concept of the Volk—a idealized, heroic, racially superior German people that had been unjustly dethroned and debased by an “international order” imposed by the Allied powers after World War I, and which must re-assert its dominance first in the German homeland, then in Europe and beyond.

This doctrine was framed in a context of racial hierarchy, defined according to a set of physical, mental, and temperamental traits. The so-called Aryan and Nordic races at the top, and the African races, as well as the Slavs, the Roma, and the Jews, were at the bottom. Hitler and the Nazis held a particular contempt for Jews, blaming them for Germany’s defeat in WWI and labeling them as a nefarious racial “enemy within” bent on weakening and destroying the Volk.

Central to Nazi policy was the notion of “racial hygiene” (Rassenhygiene), a medico-social ideology rooted in genetics and social Darwinism, which viewed human affairs as an existential competition between races, and which obligated the German Volk to promote procreation of its most “fit” people, while simultaneously purifying itself from those deemed “racially undesirable” or “genetically unfit.”

This was formerly codified in the Nuremberg Laws of 1935, which stated that only people of “German or related blood” were eligible to be Reich citizens, and which forbade intermarriage and interracial sexual intercourse. It also imposed a wealth tax of up to 90% on Jews or any other newly disenfranchised people who sought to emigrate out of Germany.  

Under these laws, couples had to obtain certificates of “biological fitness” before they could marry. Access to all public social support services was closed to all individuals deemed impure or unworthy.

Responsibility for enforcing the Law for the Protection of German Blood and German Honour –one of the two key Nuremberg Laws–fell largely on the public health offices. The practice of medicine in this context became an endeavor to strengthen the Volkskörper (the German national body) and prepare it for the arduous task of conquest and empire-building.

A 1939 public health service handbook stated that “Every measure, undertaken in all areas, must be examined from the point of view of population policy, and care for heredity and race.”

In essence, the Nazi racial hygienists—many of whom were physicians–sought to apply principles gleaned from the nascent science of genetics, and from centuries of animal husbandry, to control human reproduction. The Lancet report notes that Rudolf Hess, Hitler’s deputy Führer, once described National Socialist doctrine as, “applied biology,” and called the regime a “biopolitical dictatorship.”

“Applied Biology” & “Ballast Lives”

Eugenics was the practical manifestation of racial hygiene. By 1931, even before Hitler took power, the writings of three German racial theorists—Erwin Baur, Eugen Fischer, and Fritz Lenz—were compiled into a multi-volume textbook, the title of which translates as: Human Heredity Theory and Racial Hygiene

This book was a cornerstone of Nazi public health policy. It codified the notion that left unchecked, “lower races” could—and would—contaminate “higher races” leading to physical and social degeneration. To prevent this, the racial hygienists called for the outlawing of racial mixing, and the elimination of “counter-selective forces.” That meant people of mixed-race heritage, people with hereditary illnesses, those with physical or mental disabilities, and those with irremediable character flaws like alcoholism and drug addiction.

These people were considered “ballast lives” (Ballastexistenzen)”—people with no inherent worth, who weighed down the healthy body politic.

The Reich enacted the Law for the Prevention of Hereditarily Diseased Offspring in 1933, which called for the forced sterilization of women and men who were physically or mentally disabled, “criminally insane,” or “feebleminded.” That latter was a catch-all term applicable to many different types of people the regime considered unworthy.

“Physicians (especially psychiatrists) and other health professionals not only spearheaded the crafting of the sterilisation law, but also played crucial roles at each step of implementation. Their contribution to the law’s enforcement began with the mandatory reporting of patients judged to be hereditarily diseased,” write the Lancet commission authors. Medical practitioners also carried out the sterilization procedures, typically done surgically or via x-ray exposure.

The Lancet points out that the principles of eugenics had wide currency at the time, not just in Germany, but in many other parts of the world. In fact, the Nazis’ sterilization law was partly based on legislation drafted by American eugenicist Harry Laughlin. Indeed, 12 US states including Indiana, Connecticut, Virginia, Oklahoma, and California, had forced sterilization laws on the books at some point in the early 20^th Century.

The Nazis’ anti-Black racial policy led to the extralegal forced sterilization of an estimated 600-800 children born to White European mothers and African fathers who had served as soldiers during the French occupation of the Rhineland after WWI.

The Lancet authors estimate that in total, between 310,000 and 350,000 people were forcibly castrated or ovarectomized under the Nazi eugenics program. But sterilization was just the beginning.  

In 1939, the Reich authorized Aktion T4, “a centrally organised patient mass murder programme.” Named forTiergartenstraße 4, the Berlin address where the program was headquartered, this policy mandated “mercy deaths” for people with disabilities, mental illnesses, or any other sort of incurable condition.

Physicians and midwives were mandated to provide the government with detailed information about all children with disabilities, who would subsequently be assessed by medical panels tasked with selecting which children could be “remediated” and which were to be killed. Under the Reich Committee for the Scientific Registration of Serious Hereditary and Congenital Diseases, the state established a network of 30 “special children’s wards” where children were given “good deaths” to free them from “lives not worth living.”

Between 1939 and 1945, an estimated 300,000 adult patients in psychiatric hospitals throughout Germany, Austria, occupied Poland, and other regions of Eastern Europe were culled and exterminated under Aktion T4. The infrastructure and methods for mass murder which defined the Holocaust —including the use of poison gas—were developed under Aktion T4.

And all of this was willingly overseen and implemented by medical personnel.

Willing Physicians

The Lancet authors point out that no civilian physicians were forced to participate in the T4 program, and that “many in the psychiatric elite advocated for the killing of patients deemed incurable, to enable specialists to focus on patients who could be healed and thus improve the reputation and influence of their profession.” Others who participated willingly were motivated by an ardent belief in Nazi ideology and racial hygiene theory.

One such enthusiastic participant was Hans Asperger, the Viennese pediatrician notable for his groundbreaking studies of atypical neurology in children, and for whom the Asperger Syndrome is named.

Asperger was a self-avowed “Austrofascist,” and Catholic eugenicist. During WWII he was one of many doctors who evaluated children according to their fitness or unfitness for integration into the German volk. Those he deemed unfit, he sent to the Am Spiegelgrund clinic (literally the “mirror-ground”), a T4 killing site in Vienna. During the war years, 789 children at Am Spiegelgrund were “euthanized” via gas poisoning, lethal injection, or deliberate starvation.

In addition to racial hygiene, there were also economic rationalizations for the state-sanctioned killings. By eliminating the “incurable,” hospital beds and medical resources would be made available for treating wounded soldiers, or Germans with treatable conditions.

Many victims of Aktion T4 were ethnic Germans, and by 1940, people within Germany—including the influential Catholic leader Archbishop Clemens August Graf von Galen –voiced opposition to the program. This prompted the regime to officially end it in 1941, at least on paper. In reality, the systems set in motion by Aktion T4 simply continued in the concentration camps that the Nazis built for extermination of Jews, Roma, gay people, political prisoners, and others.

The Lancet report notes that many medical personnel who ran T4 kill centers were reassigned to concentration camps. One example is Irmfried Eberl, an Austrian physician who ran two T4 “clinics,” and who was subsequently transferred in 1942 to the notorious Treblinka camp in Poland. In a period of 6 weeks, Eberl oversaw the murder of approximately 280,000 Jews. He was dismissed for failing to effectively conceal the realities of Treblinka from the neighboring villages.

Human Experiments

Beyond their role in justifying, systematizing, and facilitating mass murder, Nazi physicians and biomedical researchers also established a heinous program of experimentation on human subjects.

This, the Lancet commission points out, is especially ironic because at the turn of the 20^th century, Germany was the first country to institute formal medical ethics guidelines for human research.

Back in 1900, the Prussian Ministry of Cultural Affairs issued a ruling against experimentation on humans without consent, in response to a scandalous experiment in which healthy women and children had been intentionally exposed to syphilis. It came three decades before the notorious Tuskegee study in which US Public Health Services researchers deliberately infected 400 African-American men with syphilis.

In 1931, the German Ministry of the Interior posted guidelines requiring that human subjects give explicit consent to participate in research, and only after appropriate instruction and education.

Though these rules were technically still in force under the Nazis, the new Reich interpreted them as applying only to members of the “German national body, but not to those excluded from it.” Enemies of the volk deemed “untermenschen” (literally, “under-men” or “subhuman”), were fair game for research.

The untermenschen—a term the Nazis applied to Jews, Roma, Slavs, Blacks, mixed-race people, homosexuals, people with disabilities, Communists, anti-Nazi dissidents, and prisoners of war–were human enough for any data obtained from them to be relevant to the German volk, but not human enough to be protected under guidelines limiting human experimentation.

Medical historian Paul Weindling and colleagues have carefully documented 300 human experiments involving at least 27,000 people, conducted by Nazi physicians and researchers during the war. These experiments covered a broad range of scientific questions. But they all aligned with core Nazi doctrines and goals: supporting the war effort, achieving German economic autarchy, eastward expansion of the Reich, and strengthening the health of the German race.

Research on concentration camp inmates included studies of physiology under extreme physiological stress like hypothermia or high altitude; control of infectious and insect-borne diseases; effects of chemical and biological weapons; human reproduction and mass sterilization; genetics and hereditary biology.

Josef Mengele is the most notorious Nazi physician. He oversaw the prisoner “selections” at Auschwitz-Birkenau, determining who was fit for forced labor and who was to be gassed immediately. He headed the “infirmary” in the camps, where he ran a number of experiments on prisoners.

Mengele was particularly interested in identical twin sets, using one twin as the experimental subject and the other as the control. Among his goals was to aid racially-superior couples to produce more twins thereby speeding the growth of the Aryan population.

He was also determined to develop blood tests that could reliably and irrefutably detect someone’s race. And he also ran disinfection and disease control studies which involved deliberately infecting prisoners in order to test experimental treatments.

“Mengele’s research practices were marked by extreme brutality and a complete disregard for the humanity of the people forced to participate, as well as the unscrupulous exploitation of the resources and atrocious context of the Auschwitz camp,” write the Lancet authors. The doctor was known as Todesangel (Angel of Death) for good reason.

“New Opportunities, Deregulated Spaces”

Mengele may have been extreme in his ruthlessness, but he was certainly not unique in his zeal.

“Medical scientists interested in pursuing research projects were generally aware of what they saw as new opportunities for research in the deregulated spaces created by the Nazi regime, where legal and ethical rules could be ignored,” writes the Lancet commission.  

One example is Carl Clauberg, a gynecologist and fertility researcher who specifically requested permission from SS director, Heinrich Himmler, to set up a sterilization research project in Auschwitz. Similarly, SS physician Karl Gebhardt saw his assignment to Ravensbrück as an opportunity to test new sulfonamide drugs on prisoners of war deliberately inflicted with “standardized” wounds intended to simulate battle wounds.

The concentration camps were also a boon for anatomy labs at German universities. According to the Lancet report, academic centers now had easy access to human cadavers from the euthanasia programs, forced labor camps, and concentration camps.

A Catalog of Horrors

The 70-plus page Lancet report is a catalog of horrors difficult to fathom. Yet each statement in the report is referenced and well-substantiated. In aggregate, the evidence clearly shows “the cooperation between civil medical research institutions, military medicine within the German armed forces and SS, and the pharmaceutical industry.”

The report dispels several widely held, comforting notions that propagated widely throughout the medical world in the post-war era. One is that the medical atrocities carried out by the Nazis were the work of a small number of radical fanatics—the “a few bad apples” thesis.

Though there were many medical professionals who did resist the racist policies of the Reich, the Lancet report shows that the majority of physicians willingly participated.

“The historical evidence provided here will show that physicians joined the Nazi Party and its affiliated organisations in higher proportions than any other profession,” the authors note, adding that, “The convergence of professional interests with political motives partly explains the gravitation of many physicians towards Nazism: by 1945, 50–65% of German physicians had joined the Nazi Party, a much higher proportion than in any other academic profession.”

The Lancet authors also challenge the notion that the Nazis had no concept of medical ethics. In truth, all the horrors of the Holocaust occurred under a clearly articulated set of ethics crafted for the service of political, economic, and racial aims. 

“Nazi Germany developed a specific form of ethics that put the health of the German people above all else, but that excluded vast numbers of individuals from being considered part of the German people according to eugenic, antisemitic, and other racist criteria. Thus, medical ethics became another instrument to help design, rationalise, and implement the regime’s eugenic and racist agenda.”

Within its own racist notions of public health, the Nazi medical establishment went to great lengths to promote the wellbeing of the Volk. The Reich established one of the world’s first public tobacco cessation campaigns, and it also actively promoted healthy whole-food diets. It ran prenatal health services and family support programs—but again, only for Germans deemed fit and worthy of them.

After the war, 23 Nazi medical personnel were brought to justice during the Nuremberg Doctors’ Trial of 1946-47, and 7 were sentenced to death. But the vast majority of those who perpetrated medical atrocities during the Nazi era—including Josef Mengele—were never captured or prosecuted.

The Lancet Commission on Medicine, Nazism, and the Holocaust: Historical Evidence, Implications for Today, Teaching for Tomorrow is not an easy read. But it is an important one.

The authors effectively describe how the horrors of Nazi medicine emerged not from irrational rage, but from principles, ideologies, and worldviews prevalent throughout academia in 19^th century Europe.

As much as it is a history lesson, the Lancet report is a cautionary tale.

The dangers of overly reductionistic thinking, medical industrialization, and co-optation of medical ethics by political agendas are with us today.

“In the Nazi era, science, medicine, and public health were used to justify and implement persecutory policies and eventually state-sanctioned mass murder and genocide. Studying the history of medicine during Nazism reveals the dangerous potentials of modern medicine, which coexist with medicine’s immense power to benefit humanity. The significance of this history is not limited to the descendants of the victims and perpetrators and their societies: it is relevant to communities worldwide—not least because early 20th-century Germany pioneered so many aspects of modern medicine that were adopted to varying degrees in many countries.”

END