Skin cancer and screening: The good and the bad of ‘overdiagnosis’

About a decade ago, when he was a first-year dermatology resident, Adewole Adamson learned that “exploding” rates of melanoma were a pressing problem. That was — and still is — the official position of the American Academy of Dermatology. Since the mid-1970s, the incidence rate of melanoma, a potentially deadly cancer, has skyrocketed sixfold; once relatively rare, melanoma is now one of the most commonly diagnosed cancers in the U.S., according to the American Cancer Society.

A few years later during a research fellowship, Adamson dug into what was behind the epidemic. He was surprised to find that diagnosing more cancers wasn’t saving more lives. Mortality remained “stone-cold flat” for decades, said Adamson, who is now an assistant professor at the University of Texas at Austin’s Dell Medical School. Only recently have melanoma deaths declined, thanks to new treatments for advanced cases. Furthermore, evidence suggested that the culprit most commonly blamed for skin cancer — exposure to ultraviolet (UV) radiation from the sun or tanning beds — couldn’t account for the dramatic rise in melanoma diagnoses.

Dr. Adewole Adamson. Credit: Kelly Davidson Studio

Adamson and collaborator H. Gilbert Welch, a senior investigator in the Center for Surgery and Public Health at Brigham and Women’s Hospital in Boston, tried for a year without success to publish a paper showing that UV exposure wasn’t the primary driver of the epidemic. Reviewers didn’t dispute the science, but they expressed concern that the findings might deter people from protecting themselves against the sun.

To overcome deeply ingrained notions about UV exposure and melanoma, Adamson said they needed to tell a fuller story. If not UV, then what is responsible for pushing melanoma rates ever higher? In an analysis published in the New England Journal of Medicine earlier this month, Adamson, Welch, and Benjamin Mazer, a pathologist at Johns Hopkins Hospital, make the case that medical care is to blame. By screening more people, doing more biopsies, and classifying more ambiguous lesions as cancer, health care providers have been “overdiagnosing” melanoma, flagging too many harmless skin spots that would have never proved harmful.

Overdiagnosis is a well-established — and many would say unavoidable — consequence of screening the general population for disease. The problem is particularly pronounced with cancer, where increased surveillance and new diagnostic tools allow physicians to detect small irregularities that might not be destined to spread. In a 2019 analysis of four decades’ worth of cancer statistics, Welch laid out how, for certain cancers, screening has driven up case numbers without reducing deaths. As with melanoma, for example, diagnoses of thyroid and kidney cancer have risen dramatically, while people are dying of those diseases at much the same rate as in 1975.

The pandemic pressed pause on many health screenings, providing an opportunity, I noted in a recent column, to look more closely at when routine checks help and when they are more likely to lead to unnecessary follow-up tests and treatments. In that spirit, the authors of the New England Journal of Medicine analysis advocate seizing this moment to reevaluate recommendations for skin cancer screening.

screencapture undark org risk covid routine screenings

Many in the dermatology community vehemently disagree. The New England Journal of Medicine published the analysis in its “Sounding Board” section, which much like this column is a space for evidence-based commentary. “Reasonable people can look at a set of facts and come to different conclusions,” said American Academy of Dermatology President Bruce H. Thiers, adding that the journal should also have published a dissenting view.

The primary goal of screenings is to reduce deaths from melanoma, said Martin Weinstock, a professor of epidemiology and dermatology at Brown University. “If the price of reducing deaths from melanoma is too many biopsies and misleading diagnoses, that’s a price that’s worth paying.”

And yet, unnecessary cancer diagnoses have underappreciated physical, financial, and psychological harms, argues Adamson. And beyond that, he said, science — and by extension patient care — suffer when we gloss over uncertainties.

Last year, 100,000 Americans were diagnosed with melanoma and a roughly equal number with melanoma in-situ, a condition in which the cancerous cells are confined to the top layer of the skin. In-situ cancers and deeper lesions that have not spread are almost always curable. But when skin cancer spreads to other structures nearby or the lymph nodes, the five-year survival rate drops to 65 percent even with treatment. Until recently, the median survival for patients whose cancers had spread to other organs was only 8 to 12 months. But new treatments that combine immunotherapy and radiation have lengthened survival to several years for many patients.

Melanoma runs in families and it’s also more common in people with lowered immunity, said Weinstock. Melanin, the pigment that gives skin its color, helps block UV rays, which is why people with darker skin have a much lower risk of skin cancer than those with lighter skin.

Studies examining the effect of sun exposure and tanning beds show that exposure to UV radiation approximately doubles the risk of melanoma. But that doesn’t explain the extent of the increase in melanoma diagnoses, says Adamson. Even if no one in the 1970s had a history of sunburns and everyone did today, the effect would be to double the incidence rate of melanoma in the population — not push it six times higher.

What is driving the epidemic, according to the authors of the New England Journal of Medicine analysis, is a more aggressive approach to screening, biopsies, and diagnosis. Dermatologists have a financial incentive to do biopsies, said study co-author Mazer. For most physicians, it’s illegal to profit from referrals of Medicare and Medicaid patients to other medical service providers. But there are exceptions for common dermatopathology services. “Every biopsy they take, they get extra money, and, historically, skin biopsies have paid very well,” said Mazer. “It’s a good business.”

Today, the vast majority of biopsies are of small, thin lesions that under a microscope can be hard to diagnose, said Mazer. “There’s no one trump card, no one criteria really that can tell us this is absolutely, without a doubt melanoma.” Even expert skin pathologists frequently disagree when discerning harmless moles from early cancer according to a 2017 study in the British Medical Journal. Due to fear of litigation or other factors, doctors tend to err on the side of diagnosing a cancer, which helps explain why melanoma in-situ is 50 times more common now than it was in 1975.

“For sure there’s some overdiagnosis,” Weinstock said. “It’s true of other forms of cancer and it’s certainly true in melanoma where there is even more ambiguity.” But, he added, compared to 50 years ago, there’s certainly a biological increase in melanoma due to UV exposure as well. Studies that try to pinpoint the degree of risk should be taken with a grain of salt, as they are based on the sometimes unreliable memories of the persons being interviewed. “There’s a lot of uncertainty,” said Weinstock.

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Thiers, the American Academy of Dermatology president, said that an aggressive approach to prevention and treatment is entirely appropriate for a disease that kills 20 Americans each day. It is difficult to determine which pigmented lesions are benign and which may turn deadly, he said, so the primary treatment is to excise the aberrant spot. “This is a small price to pay for peace of mind and far outweighs the risk of missing melanomas that could spread.”

How do you reduce overdiagnosis while not increasing the risk of overlooking potentially deadly cancers? In my conversation with Adamson, I pointed out that I don a hat and put on sunscreen when going outside for very long and report odd skin growths to my doctor. My husband, who sports a constellation of spots across his back, gets semi-regular skin cancer checks. All entirely appropriate actions, said Adamson, who specializes in treating people at high risk for melanoma. However, the most important step towards stopping the overdiagnosis cycle, he and his colleagues write, is to stop spending time and resources screening people who are not at higher risk.

Not surprisingly, Thiers disagrees. Since 1985, dermatologists have conducted more than 2.8 million free cancer checks through the organization’s public screening program, identifying more than 278,000 suspicious lesions and more than 31,500 suspected melanomas, he said. The AAD will continue to screen all comers when it’s safe to do so. “Since skin cancer, including melanoma, is highly treatable when detected early, the AAD’s free SPOT me Skin Cancer Screening Program may have helped save patients’ lives,” said Thiers. Weinstock would also expand screening, ideally, he said, by training primary care providers to do skin checks as part of routine exams.

Mazer strongly advocates for severing the financial relationships between health care providers who do the biopsies and those that examine them. That’s also a nonstarter for Thiers. In a position statement, the AAD supported the right of dermatologists to do the pathology work themselves or send it to a lab where they have a financial stake.

Some other recommendations in the New England Journal of Medicine analysis — such as limiting biopsies only to lesions larger than a pencil eraser — seem unlikely to happen in actual practice. The authors raise concern that the growing use of a lighted magnifying instrument for looking at the skin, called a dermascope, has led to more biopsies of small, harmless spots. Adamson advocates for more limited and judicious use of these devices. But Weinstock disagrees “I don’t think removing diagnostic tools from your toolbox is the answer,” he said.

Ultimately, there’s no simple fix when you are caught up in a decades-long arms race to identify more and more cancer, said Mazer. “If one side unilaterally disarms, they are called evil, uncaring,” he said. “You need pathologists, dermatologists, and patient groups, and government regulators and other policymakers to all be in agreement about this — to come together and say, ‘this is in our best interest’ — because that’s how you get these things to change.”

The heart of the debate seems to be whether people acknowledge a downside to overdiagnosis. The harms are very real, said Adamson. To start, a cancer diagnosis can prevent you from getting life insurance or short-term health insurance. It can also change how people see themselves. Adamson said that some of his melanoma patients feel guilty because they think they caused their cancer or resign themselves to spending less time outside. “I’ve had patients tell me, ‘My quality of life has diminished,’” he said.

He also worries that the problem will worsen as the system is flooded with benign abnormalities and slow-growing cancers that are not destined to spread beyond the skin. That data is then used in studies to determine peoples’ risk, as well as to train artificial intelligence systems on what cancer is and isn’t.

Adamson acknowledges that highlighting the uncertainties surrounding melanoma could muddy public health messaging. He has sympathy, he said, for those who say “I don’t want to confuse the public, I want to exaggerate a little bit to get people to do the right thing.” But nuance is important. The assumption that time outdoors has caused a skin cancer epidemic is reflected in public health advice that everyone wear sunscreen, for example, even though, as Adamson showed in a recent JAMA Dermatology analysis, there’s very little evidence that UV exposure is linked to the disease in people with darker skin.

Given that advanced melanoma is such a devastating, intractable disease, I asked Adamson: Why focus on questions of overdiagnosis that most of his colleagues don’t appear to want answered?

“Fundamentally, I think because it’s being honest,” he said. “It’s the truth.” With answers we may be able to give people better advice, better use our health care resources, or even identify some risk factor that we’ve been missing, he added. “We need to have some humility about what we know, we don’t know, and not trivialize risk, but also not exaggerate it.”

Teresa Carr is a Texas-based investigative journalist and the author of Undark’s Matters of Fact column. Find Teresa on Twitter @TeresaRCarr

A version of this article was originally posted at Undark and is reposted here with permission. Undark can be found on Twitter @undarkmag

Viewpoint: What’s the future of individualized medicine when you factor in ‘racial’ and genetic differences?

COVID-19 has put race-based health disparities on full display, but such inequities extend far deeper than the current pandemic. An enduring challenge for physicians and scientific researchers has been to distinguish health differences that result from genetic predispositions from those that arise due to environmental or social influences.

In a new commentary in the Journal of Clinical Investigation, experts from the University of Pennsylvania and Case Western Reserve University provide a historical context and contemporary examples of what they call the “quagmire” surrounding race and genetic ancestry when it comes to identifying—and preventing—health disparities.

[Editor’s note: See an excerpted version of the commentary here: Study — Quagmire surrounds the use and and misuse of race in identifying and preventing health disparities.]

Giorgio Sirugo, a senior research investigator in the Perelman School of Medicine; Sarah Tishkoff, a Penn Integrates Knowledge Professor in the Perelman School of Medicine and the School of Arts & Sciences; and Scott Williams, a professor in the Case Western Reserve University School of Medicine all have a deep background in the study of human genetics. Their research has overturned the notion that race has a biological basis, yet they say race continues to be misused as a proxy for genetic ancestry and ethnicity when it comes to medical diagnosis, treatment, and outcomes—often with harmful consequences.

Giorgio Sirugo, Sarah Tishkoff, and Scott Williams. Credit: University of Pennsylvania

Penn Today spoke with the authors about their article, including their thoughts on the misuse of race in medicine and how new investigations into human diversity could improve and personalize health care.

What compelled you to write this commentary now?

Williams: We’re sitting at a time where there’s an increasing awareness of health disparities, across the U.S., in particular. With COVID-19 differentially affecting populations, I think we’re sensitized to the features of disparities and what’s causing them. This discussion, which has come to a head over the last year, has a lot of political baggage. We think that the science has to come prior to the policy and prior to the implementation of practice.

Tishkoff: We very intentionally published this commentary in the Journal of Clinical Investigations to reach clinicians. It’s important for clinicians to understand the question of whether or not race is important for addressing clinical questions, diagnostics, or predictions of risk. When should it be used, when should it not be used, how is it useful for biomedical research, what can we use to replace race? Our research has shown that the so-called races, as defined in the United States, don’t correlate clearly with patterns of genetic diversity.

You note that race as a classifier for humans is based on historical beliefs that have since been overturned and doesn’t align with what you and others are finding out about actual human diversity. Can you elaborate on that mismatch?

Sirugo: In the commentary we explained very briefly the historical basis of some beliefs about why certain populations considered themselves superior and others inferior, and why these don’t have a basis in science. The adjective Caucasian, for example, was introduced into the scientific literature in the 18th century and has persisted to this day, when it is in fact a cultural fossil that is still used, without justification, in lieu of “European ancestry.” In medical practice in Italy, we never use the word the word race, ‘razza,” because of connections to the fascist regime that specifically targeted the Jewish population through discriminatory legislation, “Leggi Razziali’ i.e. “Racial Laws,” and ended with the murder of thousands of Italian Jews, sent to the gas chambers of Auschwitz and other death camps.

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Tishkoff: Historically racial classifications have been based on superficial things, like skin color and morphological characteristics, but have also been intertwined with cultural classifications and with a hierarchical type of thinking. In biomedicine, it depends on the particular question that you’re addressing, but it’s typically much better to talk about where people come from, what’s their genetic ancestry.

It’s also clear from the genetic data that there are no clear boundaries in terms of genetic ancestry that correlate with what we call races in the U.S. So-called Hispanic races have differing amounts of African, European, and Native American ancestry. And in people who self-identify as African American, genetic studies have shown that African ancestry is 80%, on average, but can range from less than 10% to 100%. Ultimately, we really need to have more personalized precision medicine that’s looking at individual variation and avoid racial profiling in medicine.

Williams: The definitions of race actually vary in different parts of the world, but in the U.S. we talk about African Americans, European Americans, or Hispanics as if they are homogenous groups, and they are completely non-homogeneous groups. As we’ve studied for years, there is so much diversity in Africa that to give it one nominal description is completely ridiculous in terms of genetics, in terms of ethnicity, and in terms of culture. It does a disservice on so many levels.

What are some ways that race is currently misused in medicine?

Sirugo: In childbirth planning for more than a decade, OB-GYN doctors have used a clinical decision calculator to predict the likelihood of a successful vaginal delivery after a prior cesarean delivery. The original calculator included the age, height, weight, and race of the patient. For a subject of African ancestry, it would have determined a C-section to be the most appropriate choice, and so many African American women were subjected to a surgery that was unnecessary. Race as a risk factor was eventually removed this year, and a new version of the calculator was released.

Credit: Damon Dahlen/Huffington Post

Williams: In the article we discuss the use of rosuvastatins, a drug to lower ‘bad’ cholesterol. Asians, on average, have higher circulating drug levels, but it turns out that’s due to two genes that differ in frequency between people with European ancestry and Asian ancestry. So, clinicians tend not to give that drug to Asians or Asian Americans when some could benefit from it, if we knew what their genotype was at those two genes.

Tishkoff: Another example would be cystic fibrosis, which is thought of as a disease that is only found in people of European ancestry. And again you have to be careful to avoid racially profiling someone who has mixed ancestry. The majority of an individual’s genome may be of non-European ancestry, but the genetic region that carries the mutation causing cystic fibrosis could have 100% European ancestry. So that diagnosis could be missed or delayed.

Sirugo: Yes, there’s a kind of misleading effect orienting the clinical reasoning that could bring you to the wrong conclusion.

With medical conditions that are more prevalent in people with particular ethnicities, how much do we know about whether these differences are attributable to genetics or to socioeconomic, environmental, or cultural factors?

Sirugo: One good example is that the Pima of Arizona have the highest prevalence of diabetes in the world. Over 50% of the population has it. As we stated in the paper, Pima from Mexico have a prevalence under 10%. And so you have exactly the same ethnic group with the prevalence of a given disease, which likely has a genetic component, changing dramatically depending on which environment they’re living in.

The Young River’s People Council, composed of 14 to 24-year-old Pima-Maricopa community members taking a proactive role in government and community leadership. Credit: Young River People’s Council

Williams: The traditional way of phrasing it is ‘nature or nurture.” I think its nature and nurture. There are people who have predispositions based on their individual genetic constitution where the risk is variable based on the environmental exposure. Another example we give in the paper relates to preterm birth. It’s about 50% more prevalent in African Americans than in European Americans. It’s less common in Canadians of African descent, by about 30%. But if you take first-generation immigrants from Africa, they don’t have an increased risk of preterm birth, but the second generation does. Clearly this is a response to new environmental exposures that change the risk of disease, as genetics will not change in a single generation. And even if there are genes that affect preterm birth risk, which there likely are, they are not predominant in this scenario.

One thing we don’t address explicitly in the paper is there’s a difference between the risk of acquiring a disease and the outcomes and severity of that disease. There may be biological factors that govern that, but oftentimes it’s access to health care that determines whether or not you get good treatment. Just look at the disparities observed for COVID-19 as an example.

How can health care providers address health disparities in a way that acknowledges differences without making assumptions based on what they perceive as a patient’s race or ethnicity?

Sirugo: There’s a need to bring up a generation of physicians who are a lot more aware of some of the points we have been discussing so far: the effect of genetics and the amount of variation among populations. Even in this we are biased, as a lot of research has been done in European populations, a lot less in other populations. This is part of an educational process that will take some time to correct.

Tishkoff: It seems to me that knowledge of ancestry in a patient is important and can play a role in diagnosis and treatment of disease; however, a physician has to be aware that there are no firm boundaries in terms of the genetic variation observed in groups around the world. Ultimately, we have to treat the individual.

Williams: If you’re trained as a genetics student, you will think about genetics as being important, and if you’re a social epidemiologist you will think about social factors being important. We have to be very careful about walking that line and trying to be inclusive in our intellectual approaches to how we study these things.

What do you see as the frontier in terms of individualized medicine when it comes to considering ancestry? Is it sequencing everyone’s genome?

Tishkoff: What if we had the ability to obtain a patient’s genome for $1,000, would that be the solution? I say no. Even if we had the genome of every person on this planet, until we figure out what the functional variation is, it’s not going to do any good. That also ties into the problem that Europeans are overrepresented in human genetics research. As we showed in a prior paper, about 80% of individuals included in genome-wide studies of disease risk are of European ancestry. Only around 2% are of African ancestry and 1% of Hispanic ancestry. That’s really problematic. That’s exactly the reason that we started our Center for Global Genomics and Health Equity, to address these issues.

Williams: We also have to understand there are situations in which genetics has almost no role. Take lung cancer, which, in the early part of the 20th century was an exceedingly rare disease. In the U.S. it’s not anymore and it’s almost all due to smoking.

Sirugo: Or let’s take the example of infectious diseases. We know that there is a genetic susceptibility and an environmental susceptibility. Early exposure to certain infectious agents can also increase the risk of severe outcomes of later exposure to other diseases. It’s a very complicated area, and a lot more research needs to be done.

Williams: Everybody in the U.S. talks about precision medicine, what used to be called personalized medicine. One of the reasons we do what we do is because we want to prevent disease and improve health. We want to get our knowledge of genetics to the point where there’s enough biological understanding that we can mitigate disease risks. But we have a long way to go.

Giorgio Sirugo is a clinician scientist and senior research investigator in the University of Pennsylvania Perelman School of Medicine.

Sarah Tishkoff is the David and Lyn Silfen University Professor in the Department of Genetics in the Perelman School of Medicine and the Department of Biology in the School of Arts & Sciences at the University of Pennsylvania and director of the Penn Center for Global Genomics & Health Equity. Find Sarah on Twitter @SarahTishkoff

Scott Williams is a professor in the Department of Population and Quantitative Health Sciences and the Department of Genetics and Genome Sciences in the Case Western Reserve University School of Medicine. Find Scott on Twitter @scottmwilliams9

A version of this article was originally posted at Penn Today and has been reposted here with permission. Find Penn Today on Twitter @penn_today

GLP Podcast: Cell-based breast milk; Joe Mercola’s awful COVID book; More mRNA drugs coming soon?

Cell-based breast milk might offer mothers and babies a better alternative to expensive formula in the coming years. Alternative health champion Joseph Mercola has turned the COVID-19 pandemic into a lucrative, science-free marketing opportunity. Pharmaceutical companies used groundbreaking mRNA technology to develop coronavirus vaccines. Scientists are using the same platform to develop other important therapies, including cancer and flu vaccines.

Join geneticist Kevin Folta and GLP contributor Cameron English on this episode of Science Facts and Fallacies as they break down these latest news stories:

Recent genetics research has shown that some mothers aren’t able to breast freed, or at least can’t produce enough milk to sustain their newborns. Using technology similar to that used to make lab-grown meat, a biotech startup is developing cell-based breast milk for individual women. In the coming years, the technology could offer mothers and babies a potentially better alternative to formula.

Dr. Joe Mercola, champion of all things alternative health and vocal vaccine critic, has been very active over the course of the COVID-19 pandemic. Alongside Organic Consumers’ Association founder Ronnie Cummins, the physician-turned-supplement salesman has authored a book alleging that SARS-COV-2 is an engineered bioweapon the elites have used to expand their global influence. What’s wrong this story? Almost everything. The bigger problem, however, is that figures like Mercola distract people from real problems that need to be addressed before the next pandemic comes along.

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The first COVID vaccines were developed in a matter of weeks, thanks to mRNA-based technology that allowed scientists to target the SARS-COV-2 spike protein. Using its genetic blueprint, scientists engineered shots that train our immune systems to recognize the spike protein and mount a defense should we ever come in contact with the virus itself. The mRNA platform could yield all sorts of therapies and vaccines for a variety of diseases.

Kevin M. Folta is a professor in the Horticultural Sciences Department at the University of Florida. Follow Professor Folta on Twitter @kevinfolta

Cameron J. English is the director of bio-sciences at the American Council on Science and Health. Follow him on Twitter @camjenglish

When the faster-spreading and more virulent COVID-19 mutant came to my home town, it shook up everyone. Here’s an explainer of what it foreshadows

When a new variant of the COVID-19 virus appeared in the UK as 2020 drew to a close, I didn’t think it would show up a half hour’s drive from my home in the somewhat remote village in upstate New York soon after. The first cases were near Denver and in San Diego, and then traced to a jewelry store on Broadway in Saratoga Springs. My husband and I felt rather insulated and isolated here, hours from New York City.

The legacy of Caffe Lena

Earlier this year, I received an email from the executive director of Caffe Lena, the oldest coffeehouse in the US. Don McLean debuted “American Pie” there, Arlo Guthrie first tried out “Alice’s Restaurant,” and Bob Dylan and many others have commanded the iconic tiny stage in the small, homey establishment that opened in 1960.

The café is now in “Safe Mode,” with even the fabulous online events it has held throughout the pandemic too risky to record. The one-month shutdown follows the death January 12 from COVID of Matt McCabe, owner of Saratoga Guitar and frequent performer at the coffeehouse. The opening image captures his final show, in December.

Matt McCabe plays his last set at Caffe Lena in December. He passed away from COVID on January 12. Credit: Sarah Craig

The last time my husband and I had been to Saratoga was to dine outside Hattie’s Chicken, next door to Caffe Lena. It was that fabulously warm wonderful November Saturday when the election results were in and we felt the first faint glimmers of hope return. We watched as a few musicians hauled their instruments up the steps of the recently-refurbished Caffe. I don’t know whether Matt McCabe had the new variant of SARS-CoV-2. But now that Caffe Lena is stopping online broadcasts, I’ll have more time to write, so thought I’d explain the confusing distinctions that have made a scary pathogen even scarier: mutants, variants, and strains.

What exactly are the new guises of SARS-CoV-2? And where did they come from?

A quick science lesson

Nucleic acids – DNA and RNA – are long strings of building blocks that impart meaning. Triplets of DNA or RNA bases encode the amino acids that link into proteins, and proteins underlie traits.

The sequences of nucleic acids can change, when the molecules copy themselves, like perpetuating a typo in a document. Not all changes to RNA or DNA affect the encoded protein, but if they do, they can alter the corresponding trait. For a virus, that might be ease of transmission to a new host, strength of binding to receptors dotting the host’s cells, or hiding from the immune response.

Once a mutation happens, two major factors – a founder effect and natural selection – influence the trajectory of its spread. Both can unfold at once, as is the case for SARS-CoV-2 right now.

Chance and selection fuel change

A founder effect is when a mutation or mutations arrive at a new location through chance sampling. That’s how the UK variant ended up in Saratoga Springs.

Several variants of the virus were circulating in the UK during the fall, genomic surveillance just beginning to pick them up, when a man unwittingly got on a plane and headed for Albany. A few days later, he was shopping for a Christmas gift at the jewelry store on Broadway in Saratoga Springs, and became the first person to harbor the new UK variant in New York state. Might he have, perhaps circuitously, infected Matt McCabe?

A founder effect can deliver a novel viral variant on a smaller scale than an airplane, too. A person might harbor several versions of SARS-CoV-2, yet only one jumps to another person in a sneeze or cough.

Soon after founder effects brought new variants here, natural selection unfolded too. It’s survival of the fittest: if a new mutation benefits the virus, it persists.

The UK variant, called B.1.1.7, consists of several mutations that enable viruses to copy themselves 71% faster, spread from host-to-host more readily, and bind more tenaciously to our cells.

Credit: New York Times

Mutations, variants, and strains, oh my!

New versions of SARS-CoV-2 differ genetically, but the degrees of difference are confusing. Here’s clarification:

  • A mutation substitutes one type of RNA base for another at a single place in the 30,000-base viral genome. If the change alters the encoded amino acid in a way that changes the virus’s action, natural selection can favor it. To a geneticist, “gene mutation” and “gene variant” are synonymous.
  • A variant to an epidemiologist is broader, meaning the viral genome has something different, arising from one or more mutations. B.1.1.7 harbors nine mutations in the spike protein gene alone, the part that the immune response “sees.”
  • A strain is even broader, denoting a variant that has a telltale observable or measurable trait or behavior. A new strain may emerge from gene interactions.

It’s hard to keep up with the ever-mutating virus, and I can’t describe them all in one post. But here’s a description of three new faces of the virus that have dominated newsfeeds: D614G, a mink mutation, and B.1.1.7.

“D” versus “G” virus

The first notable COVID mutant, called D614G, popped up in several parts of Europe by early March, and then hopped planes to the US. Because it spreads more readily than whatever it mutated from, it’s taken over. D614G may have seeded Europe from China in January through a founder effect, but once there, it likely spread, fast, under powerful natural selection.

“The mutation was concerning because it looked like something new was taking over in multiple places. In evolution, that’s a strong clue that it might confer an advantage for the virus, that natural selection is at play,” said Adam Lauring, of the University of Michigan Division of Infectious Diseases in a JAMA webinar January 2. Modeling and cell experiments indicated natural selection rather than a series of founder effects.

Anthony Fauci added perspective on D614G. “RNA viruses mutate, that’s been known forever. The overwhelming majority of mutations are without any functional significance. Every once in awhile, we get one that is,” and that’s the case for the single amino acid change at position 614 in the spike, the part of the virus that binds to ACE2 receptors on many human cell types. While the mutation spreads more easily and binds tighter to receptors, the antibodies that the vaccines elicit do attack it, he reassured. But spreading more easily means more opportunities to mutate.

What D614G enables the virus to do is a little like strengthening the tailhook of a fighter plane, making it better able to latch onto a cable on the deck of an aircraft carrier. The mutation affects a specific spot in the spike, where its “receptor binding domain” intersects a loop of amino acids that reverberates like a trap door. Once a spike grabs on, a second part of it clamps down onto the cell membrane and pushes the virus through. We’re infected.

Here’s what “D614G” means in biochemical shorthand: a single RNA base change corresponding to the 614th of 1277 amino acids that comprise the spike. The mutation alters an aspartic acid (“D”) to a glycine (“G”). (Biochemistry convention represents each of the 20 amino acids with a single letter.)

The jargon behind D614G is abbreviated further to the “D” and “G” strains of the virus. D is the slowpoke, while newbie G copies itself more readily, boosting a person’s viral load so that denser clouds of virus are exhaled.

Credit: Bette Korber/Cell

But the D614G mutation may eventually exert greater significance in terms of epidemiology. A viral variant that passes to more people (ups the “R naught” value) elevates the percentage of a population that must become immune (through infection or vaccination) to achieve herd immunity. I’ll save that for another post.

The mink mutation

Next came minks. Reports from the Netherlands in the spring, and in Denmark in June with autumn resurgence, pointed to mink farms. Human workers may have initially given the virus to the minks, which then returned the favor, in changed form.

The mink mutation also alters the spike protein, and is dubbed N453Y – a change from tyrosine to phenylalanine at amino acid position 453. Studies on people who’ve recovered from COVID show that sometimes their antibodies aren’t as able to neutralize the new version of the virus, while the spikes bind more strongly to our receptors.

“The change is modest, so I don’t think it will compromise vaccines. But the big concern is a virus established in another host species where it can evolve and spill back into humans,” Lauring said. That’s why many countries are culling minks.

The UK and South African variants

The evolutionary tree diagrams that depict relationships of related species, like hippos, whales, pigs, and peccaries, are also used to track changes in viral genomes. The trees are derived from comparing DNA or RNA sequences, sometimes using mutation rates to estimate times of divergence from shared ancestors.

I think of evolutionary trees when my laptop freezes and I have to rescue the document from every time I’d hit “save.” I compare all the versions that suddenly overlap on my screen to deduce the order, from first draft to most recent.

Researchers similarly upload new SARS-CoV-2 genome sequences to the database GISAID, where bioinformatics tools convert the data into branches, called lineages or phylogenies, of evolutionary trees. (See COVID Genomes Paint Portrait of an Evolving Pathogen, here at DNA Science.)

B.1.1.7 harbors a “signature” of 14 mutations. The most notable is N501Y (asparagine changed to tyrosine at position 501).

Blasting through the UK and South Africa and beyond with astonishing speed, N501Y clearly has an advantage – that’s natural selection at work, not a slower founder effect. The fact that N501Y arose independently in the UK and South Africa also points to natural selection. “This virus grows faster and it started later, and has spread rapidly, doing a lot better than its cousins. We should pay attention,” warned Lauring.

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The UK variant has probably been more widespread here and we didn’t know it simply because we weren’t looking. “The UK has a massive operation. They sequence 10% of all SAR-COV-2 tests; in the US, we sequence probably way less than 0.5%. Other countries that also don’t do a lot of sequencing are now finding it because they’re looking harder for it now,” Lauring said.

Although B.1.1.7 doesn’t make people sicker, its more rapid spread means that more people will become infected – and the sheer numbers will send more patients to already overburdened hospitals. It’s deja vu all over again from D614G.

Preliminary studies from South Africa, where people who’ve been sick are becoming reinfected with the new variant bearing the N501Y mutation, indicate that the natural immune response isn’t making sufficient neutralizing antibodies. Vaccines are likely to offer better protection because they’re designed to coax the body to make a wider array of antibodies, tackling spikes at several points and from several angles. But if vaccine efficacy is even slightly lower than expected from testing before the new variants arrived, that’ll raise requirements for herd immunity.

Coda

The battle of humanity against the novel coronavirus seems never-ending. Evolutionary trees reveal that SARS-CoV-2 jumped to us from bats only recently – so its genome is still adapting to our bodies. The virus is a moving target.

January 20, New York’s governor Andrew Cuomo addressed the future of the changeling virus. As he reported two more cases of B.1.1.7 from Saratoga Springs, he said “it is just a matter of time” and “a matter of probability” until we will face a more deadly or vaccine-resistance coronavirus. Next week I’m writing about a machine learning algorithm that predicts mutations.

Meanwhile, what must we do, before nature attenuates SARS-CoV-2 into just another cause of the common cold? That could be years from now. Continue with the tried-and-true, if uncomfortable, public health measures – social distancing, hand-washing, and wearing masks.

Ricki Lewis has a PhD in genetics and is a science writer and author of several human genetics books. She is an adjunct professor for the Alden March Bioethics Institute at Albany Medical College. Follow her at her website or Twitter @rickilewis

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Robert F. Kennedy, Jr: Environmental lawyer partners with Church of Scientology in anti-vaccine and anti-GMO activism

Robert Francis Kennedy, Jr. (born 1954) is the third child and second son of the late Attorney General, US Senator and Presidential candidate Robert F. Kennedy (RFK). He is an anti-vaccine, anti-GMO and anti-pesticide litigator who espouses health and environmental claims that stand outside mainstream science. He promotes his views through his nonprofit, Children’s Health Defense, formerly the World Mercury Project. It was founded in 2007 and re-branded in 2018. It opposes vaccines, mercury usage in dentistry and chemical/pesticide use. Kennedy was part of the plaintiff’s litigation team in a 2018 lawsuit alleging Bayer’s weedkiller Roundup (glyphosate) causes cancer. In addition to his anti-vaccine, anti-GMO advocacy, he claims 5G wireless causes cancer and other health issues, and has embraced numerous other fringe conspiracy theories.[1]

Since the outbreak of the COVID-19 pandemic, Kennedy has repeatedly argued that all vaccines are “unavoidably unsafe”, expressing his belief that various vaccines to control the pandemic are dangerous. He has consistently attacked Bill Gates, who he accuses of masterminding a global effort to fund vaccine research in a secret plot to assume “dictatorial control of global health policy.” In August 2020, Kennedy aligned himself with radical U.S. right-wing and European extremist groups spreading conspiracy claims that the coronavirus pandemic is “one big lie” by governments and multinational corporations led by Bill Gates to enslave the public via vaccine dependency and technological tracking of their activities.[2] In February 2021, Instagram banned Kennedy “for repeatedly sharing debunked claims about the coronavirus or vaccines,” a spokesperson for Facebook, which owns Instagram, said in a statement.screen shot at pm

In August, 2020, Kennedy filed suit in federal court in California, alleging that Facebook’s fact-checking program for scientific or medical misinformation, which led them to limit anti-vaccination posts by Kennedy and other groups, violates his constitutional rights. A recent study had found that Kennedy, through his CHD organization, were responsible for more than half of the anti-vaccine advertisements on Facebook when they were permitted. Facebook removed several anti-vaccine videos and promised to stop recommending anti-vaccine pages in addition to including a label at the top of the Children’s Health Defense’s (CHD) Facebook page which informs users that “this page posts about vaccines.” Facebook also included a link to the Center for Disease Control and Prevention’s website at the top of the CHD’s Facebook and removed the group’s ability to fundraise on the social media platform. The Kennedy-led suit (PDF) claimed that Facebook, CEO Mark Zuckerberg, and the organizations Science Feedback, Poynter and PolitiFact acted “jointly or in concert with federal government agencies” to infringe on CHD’s First and Fifth Amendment rights. The suit also alleged Facebook and the fact-checking organizations colluded to commit wire fraud by “clearing the field” of anti-vaccine ads. The suit is pending, but several American judges have dismissed similar lawsuits in the past, arguing that social media companies are not bound by the First Amendment and have every right to censor users that violate its content policy.

Career

After graduating from law school and passing the New York bar, Kennedy became an assistant district attorney in New York City. From 1984 until 2017, he was a board member and chief prosecuting attorney for Hudson Valley Riverkeeper, which advocated (and litigated) for cleaning up pollution from the Hudson River. He became a staff member of Riverkeeper after serving as an intern as restitution as part of his 1983 court sentence for heroin possession. [3]

From 1986 until 2017, Kennedy was a senior attorney for the Natural Resources Defense Council (NRDC), an environmental activist group known for its opposition to chemicals and biotechnology, specifically the genetic engineering of crops. Kennedy is the president of the board of Waterkeeper Alliance, a non-profit environmental group that he helped found in 1999. For more than thirty years, Kennedy has been an adjunct professor of Environmental law at Pace University School of Law. Until August 2017, he also held the post as supervising attorney and co-director of Pace Law School’s Environmental Litigation Clinic, which he founded in 1987.[4] He is currently professor emeritus at Pace.[5]

Kennedy co-hosts Ring of Fire, a nationally syndicated American radio program for plaintiffs’ bar litigation issues.

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Education

  • Attended Georgetown Preparatory School, a boarding school in Bethesda, Maryland
  • Graduated from the Palfrey Street School in Massachusetts
  • Graduated from Harvard College – 1976 BA American History and Literature
  • Graduated University of Virginia School of Law – JD
  • Graduated Pace University School of Law – Master of Laws

Advocacy

Environment and links to the Church of Scientology

Beginning with his internship at Riverkeeper, Kennedy became an attorney-advocate on environmental issues. One of his first cases with the firm was litigation against General Electric for PCB pollution of the Hudson River.[6] Kennedy co-founded EcoWatch, an environmental news site. In 2000, he also co-founded the law firm Kennedy and Madonna, which litigates environmental pollution cases; its most recent case involved a methane gas blowout at a facility in Porter Ranch, California. After that case, Kennedy took a position as co-counsel for the law firm Baum Hedlund Aristei & Goldman, which was founded by and continues to be managed by adherents of the Church of Scientology. He became involved in litigation against the manufacturer of Gardasil, the human papilloma virus (HPV) vaccine designed to prevent cervical cancer. [7] The firm has become instrumental in other environmental litigation cases, including lawsuits against the former Monsanto Corp. involving the herbicide glyphosate. In 2017, Kennedy resigned from Riverkeeper, citing his new residence on the west coast and his work with other advocacy groups.[8]

Anti-vaccination

In 2003, Kennedy began writing articles and making statements in opposition to vaccines. [9] Since the mid-2000s, he has consistently claimed that vaccines are linked to autism in children, an allegation first made by a discredited British physician named Andrew Wakefield in a now-retracted paper published in The Lancet.[10]  Kennedy has focused his advocacy on thimerosal, a compound of mercury that had been added to vaccine formulations to prevent contamination. [11] Thimerosal has never been shown to cause harm, but the US Centers for Disease Control and Prevention and the American Academy of Pediatrics asked vaccine makers to remove thimerosal from vaccine formulations. Even though Kennedy began making claims of a vast, international conspiracy to poison children with thimerosal-laden vaccines in 2005, the compound had been removed from most immunizations beginning in 2001. [12]

As far back as 2015, Kennedy has promoted the debunked link between vaccines and autism, claiming in numerous forums that vaccines were causing a “holocaust” in the United States and other western countries. That echoed claims made by the Church of Scientology and the Nation of Islam. Through the Children’s Health Defense, he has advocated against vaccines, claiming “fraud and corruption within the CDC and the pharmaceutical industry.” [13] Kennedy says he was “fighting multiple lawsuits on behalf of Riverkeeper and Waterkeeper against coal-fired power plants” when he was also speaking about “the dangers of mercury emissions, which, by then, had contaminated virtually every fresh water fish in America.” [14]

Through Children’s Health Defense, Kennedy assumed the self-appointed role of “vaccine safety” advocate. Most of his efforts consist of continued claims that vaccines contain thimerosal, which contains mercury. Mercury is indeed a neurotoxin, and children chronically exposed to mercury from food suffer delays in the development of their nervous systems. But the chemical formula of mercury in thimerosal is very different from mercury that causes health problems.[15]

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Kennedy’s claim that vaccines are unsafe because of thimerosal minimizes nine studies funded or performed by the CDC since 2003, as well as a 2000 safety review by the Institute of Medicine that found no health risks from the compound. [15] As for autism, only the Wakefield study showed any results connecting vaccines to autism. The study has since been retracted, and Wakefield has lost his medical license for committing fraud.[10]

In 2017, Kennedy announced that he would be the head of a panel on vaccine safety, established by newly inaugurated President Donald J. Trump. The White House transition team never formed the panel.[16]

Kennedy has been the keynote speaker at many high-profile anti-vaccine events, including a joint 2013 conference put on by AutismOne and Generation Rescue, both well-known anti-immunization groups. [17], [18] Generation Rescue is headed by anti-vaccine advocate and actress Jenny McCarthy, and has issued statements against vaccines that misinterpret science. These include the claim that vaccination gave her son autism, that vaccines contain “toxins” including mercury, ether, antifreeze and aborted fetal tissue, and that she cured her son with a gluten- and casein-free diet.[19] AutismOne has issued written support for discredited researcher Andrew Wakefield, even inviting him to speak at their conference. [20]

A study published in the journal Vaccine in 2020 found that two buyers (Kennedy’s World Mercury Project–now Children’s Health Defense, and the Californian group Stop Mandatory Vaccination) were the purchasers of 54 percent of anti-vaccine advertising on Facebook. The study by researchers at the University of Maryland, George Washington University and Johns Hopkins University was conducted before Facebook changed its policies on allowing anti-vaccine advertising. [21]

In August 2020, Kennedy spoke at an outdoor rally in Berlin, protesting German Chancellor Angela Merkel’s actions aimed at reducing exposure to SARS-Cov2, the virus causing COVID-19. The rally, consisting of a hodgepodge of organizations which included right-wing extremists and even Neo-Nazis, heard Kennedy warn against the 5G cellular network and Microsoft founder Bill Gates. With reference to his uncle’s visit to Berlin in 1963, he said: “Today Berlin is again the front against totalitarianism.” [2]

Glyphosate

Glyphosate, the active ingredient in the weedkiller Roundup (first manufactured by Monsanto), has long been targeted by anti-GMO activists because several genetically modified crops (corn, soy and cotton) have been developed to withstand applications of the herbicide.

jfk monsanto
RFK JR Part of Baum Hedlund Litigation Team

Through the Church of Scientology law firm Baum Hedlund, Kennedy has sued Monsanto (now owned by Bayer) based on the claim that glyphosate causes non-Hodgkin’s lymphoma (NHL), a rare form of cancer, in workers who have applied the weedkiller. This claim is based on a 2015 monograph from the International Agency for Research on Cancer (IARC), which declared glyphosate to be a “probable” carcinogen for workers, although it found no demonstrable dangers to the general public from trace exposure in food. The monograph has been heavily criticized for its sloppy methodology; concerns have also been raised that several authors of the report had financial ties to the law firms that sued Monsanto after IARC published its findings. No other major federal hazard or risk agency in the world has concurred with the IARC findings, with many issuing direct rebuttals.[22] 

 

Despite these limitations, Kennedy (and other lawyers) have leveraged the IARC ‘hazard’ finding to trigger the Daubert rule, which is a legal doctrine that allows personal injury lawsuits to be filed once a threshold of scientific information has been reported on the substance in question. Kennedy explains his justification for suing over glyphosate to Dr. Mark Hyman, a physician and wellness advocate as well as an opponent of the use of genetically modified crops and food:[23]

In 2018, Baum Hedlund scored the first victory against glyphosate, with a $289 million verdict against Monsanto accused of giving groundskeeper DeWayne Johnson non-Hodgkin’s lymphoma. The jury decided that glyphosate more likely than not contributed to his cancer; the jury did not focus on studies showing that the causes of lymphomas are unknown; nor did they consider extensive research as noted by 16 other major research groups that there concluded there is no demonstrable link between the weedkiller and non-Hodgkin’s lymphoma. The verdict has since been reduced by other courts.

In 2020, Kennedy claimed in an article for Children’s Health Defense [24] that glyphosate and vaccines are responsible for rising obesity rates, particularly in children. The article quoted “studies by immunologist JB Classen showing vaccine induced immune overload” as a primary cause of childhood obesity. JB (John Bartholomew) Classen is an anti-vaccine activist who claims that “immunization causes a large number of other chronic diseases, including autism, diabetes, metabolic syndrome, autoimmune diseases, allergies, asthma, cancers and Gulf War Syndrome.” Kennedy then connected obesity with glyphosate by quoting MIT computer scientist Stephanie Seneff and co-author Anthony Samsel, both well-known anti-GMO and anti-glyphosate advocates with no experience in toxicology or epidemiology. The pair has alleged that glyphosate is the cause of “obesity as well as numerous other toxic conditions.”[25] While rates of obesity have indeed risen significantly since the 1980s, reputable studies have shown no connection with vaccines or glyphosate [25].

Affiliates

Quotes and Claims

“As an attorney and environmentalist who has spent years working on issues of mercury toxicity, I frequently met mothers of autistic children who were absolutely convinced that their kids had been injured by vaccines. — “Deadly Immunity,” Rolling Stone/Salon 2005 .

“Our public health authorities knowingly allowed the pharmaceutical industry to poison an entire generation of American children, their actions arguably constitute one of the biggest scandals in the annals of American medicine.” — “Deadly Immunity

“When I started reading about thimerosal, I was dumbstruck by the gulf between the scientific reality and the media consensus. All the network news anchors and television doctors were assuring the public that there was not a single study that suggested thimerosal was unsafe or that it could cause autism. After a short time on PubMed, I’d identified many dozens of studies suggesting that thimerosal causes autism and a rich library of peer-reviewed literature—over 400 published studies—attesting to its deadly toxicity and its causal connection to a long inventory of neurological injuries and organ damage.”  — Interview, Children’s Health Defense

“In fact, Cheerios have more glyphosate per serving than vitamin D and vitamin B12 which are added to enrich the cereal. It’s even been in commercial honey. So, it’s a big problem. It’s linked to cancer, it’s linked to all these health issues.” — Interview with Dr. Mark Hyman, July 2020

Criticisms

  • RFK Jr. Is Our Brother and Uncle. He’s Tragically Wrong About Vaccines, Politico, By Kathleen Kennedy Townsend, Joseph P. Kennedy II and Maeve Kennedy McKean, May 8, 2019
  • Anti-Vaxxer RFK JR. joins neo-Nazis in massive Berlin ‘Anti-Corona’ Protest by Daily Kos, August 2020 – “Tens of thousands ‘Corona-Truthers’ descended on Berlin today to protest the measures implemented by Angela Merkel and her government to prevent the coronavirus spread… The protest was organized by right-wing extremist organizations- including the AfD party and various anti-Semitic conspiracy groups as well as the neo-Nazi NPD party. Among the speakers was Robert F. Kennedy Jr.. who warned against the “totalitarianism” of Angela Merkel… Protester were seen carrying poster urging “Trump, Please Help” with the QAnon logo.” (Note: RFK, Jr had been tapped by Donald Trump to lead a White House panel inquiry into vaccine safety at the beginning of his presidency. The Panel was never convened.)
  • Robert Kennedy Jr, Antikommunist Neus Deutschland, August 2020 – “Robert F. Kennedy whipped up a mass of anti-coronavirus opponents, Nazis, conspiracy theorists and eso-hippies in Berlin. The 66-year-old received a lot of applause for his crude theses – for example that the corona pandemic had been planned for decades and would be used to introduce a digital currency that marked the beginning of slavery… (Kennedy) supported a conspiracy-theoretical pamphlet by several bishops, in which it is claimed that the measures to contain the pandemic are the “prelude to the creation of a world government beyond control…”
  • Robert F. Kennedy Jr: Anti-Vaxxer, June 5, 2013 – “RFK Jr. has a long history of adhering to crackpot ideas about vaccines, mostly in the form of the now thoroughly disproven link to autism. He’s been hammering this issue for a decade now, and his claims appear to be no better and no more accurate now than they were when he first started making them.” Phil Plait, Slate.
  • In 1995, Premier Ralph Klein of Alberta declared Kennedy persona non grata in the province due to Kennedy’s activism against Alberta’s large-scale hog production facilities.
  • In 2002, a federal judge dismissed a class action lawsuit against Smithfield Foods, Incfiled by a coalition of plaintiffs’ lawyers led by Robert F. Kennedy, Jr., and in a rare move, ruled that Kennedy and the other lawyers must pay Smithfield’s costs and legal fees. At a series of news conferences in 2001 Kennedy announced his intention to use this and other lawsuits as a means of “shutting down Smithfield’s farm operations.”

Personal

Kennedy has been married three times and publicly reported sex and drug addition problems. He was arrested for heroin possession in 1983. He’s been alleged to have sought to bribe journalists to cover up reports of his and his relatives disreputable behavior.[26]

References

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In the midst of the coronavirus pandemic, Daniel Defoe’s account of London’s 1665 bubonic plague offers a shock of recognition

Pandemics have punctuated recorded history going back to ancient Greece and Egypt. However, the novel coronavirus pandemic is unfolding in a world that is qualitatively different due to densely-populated cities, long-distance air travel, and modern medicine and genomics. So it is understandable that we assume that our experience of a pandemic in the 21st century could have little in common with that of periods predating antibiotics, vaccines, and the germ theory of disease.

But it is hubris to think that material and technological progress makes our era totally discontinuous with the past, and that the experience of epidemics of plague, cholera, and other diseases that were a regular occurrence until recently has nothing in common with what we are experiencing.

We are in the midst of what Ed Yong of The Atlantic termed a “patchwork pandemic” – characterized by different geographic areas, different population groups, and different historical legacies. While the world awaits the development of an effective vaccine as well as treatments that can tamp down the ravages of a capricious virus, public health officials are exhorting us to rely on the most rudimentary, age-old tools for keeping the virus at bay – wearing a mask, hand-washing, and social distancing and lockdowns – in other words, treating people we don’t know as potential threats. Every virus and every bacterium has its distinct personality, and, yet, looking back at the history of pandemics, the ways in which human societies have responded to the upheaval and terror provoked by a poorly-understood microorganism have striking commonalities.  For this reason, chronicles of disease outbreaks from the past can provoke a shock of recognition.

Daniel Defoe, author of the classic Robinson Crusoe, is also renowned for his classic description of an epidemic, A Journal of the Plague Year. Defoe was five years old when the bubonic plague came to London in 1665. He must have heard stories of the plague as a child, and in 1722 he published a gripping account of life during the plague. His Journal is a sleight-of-hand. Though actually a work of fiction written more than fifty years after the events, it presents itself as a contemporaneous, first-hand, neighborhood-by-neighborhood, eye-witness narrative of what life was like during the “visitation” by the plague. For his chronicle Defoe drew on a small library of contemporaneous accounts.

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Frontispiece of original edition of A Journal of the Plague Year, 1722.

Owing to the vividness and immediacy of the narrator’s description of the effects of the epidemic on ordinary people in this street or that neighborhood of the city, the Journal has become the most famous account of the Great Plague of London, displacing contemporaneous accounts by actual witnesses.

A failed businessman-turned-journalist, who started writing fiction later in life, Defoe originated a new style of writing that dispensed with aristocratic literary conventions, relying instead on empiricism and realism. His narrator tells us that his journal is based only on what he has observed directly in his walks about the city, what he has heard from credible persons, and the weekly “bills of mortality” published by the city of London. On occasion, he refers to events which he feels obliged to report but which he can’t vouch for.

As in Robinson Crusoe, the narrator of the Journal finds himself in a situation in which he must summon up all his wits and energy to survive an overpowering, incommensurate threat.  While concerned for his own safety and his business, his single-minded focus is on the impact of the plague on the city of London, which is his protagonist.  We are at his side as he describes what he sees as he moves about the city and provides his coordinates, which would have been familiar to any Londoner of the 18th century – “that is to say, in Bearbinder Lane, near Stocks Market.”  The city’s inhabitants are characterized only insofar as they are affected by the “distemper” and make decisions about how to respond to it.

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At first the plague, which the narrator tells us has come to London from Holland, manifests itself by a few isolated cases in the winter of 1664-65. But in February it flares up in parishes to the west of the city and gradually makes its way eastward, methodically visiting formerly untouched parishes. In the course of a year, it has reached every corner of England. Early in the outbreak the wealthy flee the city with their servants to their country houses, and the narrator, who initially considers fleeing, remarks that there were no horses left in the city.

In spite of his belief in Providence, the narrator emphasizes that transmission of the infection requires close personal contact, often within families, or with contaminated belongings, food, or cargo.  Although the plague may have been sent by a Divine power to punish men for their sins, he makes clear that natural causes are entirely sufficient to account for the spread of the disease and its effects on its victims.

I must be allowed to believe that no one in this whole nation ever received the sickness or infection but who received it in the ordinary way of infection from somebody, or the clothes or touch or stench of somebody who was infected before.1

He describes the high transmissibility of the plague (which we now know to be caused by the bacterium Yersinia pestis, which was spread by fleas that fed on the  black rat) and the unbearable sensitivity and pain caused by its pathognomic feature – buboes – which, he tells us, drove sufferers to throw themselves out of windows or into the Thames.  He also notes that asymptomatic cases could spread the infection and that the disease can manifest differently in different people. Houses where people took sick were shut up and padlocked by order of the magistrate, and watchmen were posted outside day and night to insure – not always successfully – that the imprisoned could not escape. The narrator describes the pitiful cries that were heard from the street as family members discovered that a loved one had succumbed to the plague.  Others, he tells us, died in the street. The bodies of the deceased were collected at night and taken to pits dug in churchyards or in open lots and buried en masse.

Defoe’s narrator describes the desperate condition of the poor, who, thrown out of work, could not buy food or other necessities for their families.  In this situation, he tells us, they had no choice but to perform the most dangerous jobs created by the epidemic – tending to the sick and collecting and burying the dead. He notes that “the plague, which raged in a dreadful manner from the middle of August to the middle of October, carried off in that time thirty or forty thousand of these very people.” Once the plague makes itself felt, the common people, who are keenly attuned to astrological signs and portents, are desperate to ward off its spread and chase after an abundant array of fake cures and elixirs:

[The common people] … were now led by their fright  to extremes of folly; … they ran to conjurors and witches, and all sorts of deceivers, to know what should become of them (who fed their fears, and kept them always alarmed and awake on purpose to delude them and pick their pockets) so they were as mad upon their running after quacks and mountebanks, and every practicing old woman, for medicines and remedies; storing themselves with such multitudes of pills, potions, and preservatives, as they were called, that they not only spent their money but even poisoned themselves beforehand for fear of the poison of the infection.2

Throughout his chronicle, the narrator anxiously scrutinizes the weekly “bills of mortality” published for each parish to gauge the progress of the infection.  He knows from observing what is going on around him that the numbers of deaths attributed to the plague are grievously under-reported due to relatives’ fear of being stigmatized and the authorities’ connivance.  He tries to judge the true magnitude of the deaths from the plague by examining increases in other causes of death and by comparing the overall death rate in a parish before the outbreak to the numbers when the plague was present all around him.

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Bill of mortality for a week summarizing deaths from all London parishes.

Deaths increased at an extraordinary rate in July and August, reaching a peak in September when, we are told, each week there were 8,000 or 9,000 deaths from the plague, and this he considers an under-estimate.  Thereafter, the deaths began to decline precipitously, and the outbreak abated. According the bills of mortality, 68,590 people died of the plague, while the narrator claims that the total reached 100,000.  This amounts to twenty percent of the population.

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Graph of weekly deaths from the plague, 1665-66, shows the peak occurring in September. From Samuel Pepys’s Diary.

Looking back at the events after a half-century, Defoe knew the outcome of the “visitation,” and his account has a taught unity of time and place.  Here in the United States, five months into the SARS-CoV-2 pandemic, many observers are watching in horror and disbelief as the virus spirals out of control in states in the South and West that failed to take it seriously and refused to learn from the experience of other states, and countries, that succeeded in bringing their outbreaks under control.  At the same time, some states and countries that successfully broke the chain of transmission, are experiencing resurgences.

ft july confirmed cases

For all the differences between the London plague and our pandemic, there are striking commonalities. As in Defoe’s London, the poor and the weak are disproportionately exposed to the coronavirus in low-income neighborhoods, close living-quarters, and low-wage jobs.  As in Defoe’s London, many people refuse to follow common-sense precautions, instead falling for quackery and scientifically unsupported treatments. As in London, statistics regarding the number of cases and deaths from Covid-19 are manipulated and misinterpreted to suit the narrative of different parties.

On the most basic level, what we share with the London outbreak is the massive, sudden upsurge in morbidity and mortality, and the inescapable sense that a pathogen is beyond our control. In London of 1665 the bills of mortality were widely distributed so that residents could know the situation in their parish, and neighbors shared the latest news of who had fallen ill and died.  In 2020, normal life has been replaced by a profusion of images, charts, statistics, and stories, which have flooded the media since March.  These convey the fever chart of the epidemic in different places together with stories of intensive care units stretched to capacity and the bios of individuals who have been lost.  At the same time, we are subjected to a constant flow of interviews with health care workers, epidemiologists, and public health officials, who interpret the day-to-day trends in an effort to explain where things are headed.

Although we pride ourselves on being modern and are used to thinking that we have control over our lives, at the present moment we have to admit that we have no idea of how this “visitation” will play itself out.

References:
  1. Daniel Defoe, A Journal of the Plague Year, Penguin edition, 1966, p. 206.
  2. A Journal, p. 30.

Geoffrey Kabat is an epidemiologist and the author, most recently of Getting Risk Right: Understanding the Science of Elusive Health Risks. Geoffrey can be found on Twitter @GeoKabat

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Eerily similar? Examining fates of the rich and poor during COVID-19 and 14th century Black Death pandemics

The coronavirus can infect anyone, but recent reporting has shown your socioeconomic status can play a big role, with a combination of job security, access to health care and mobility widening the gap in infection and mortality rates between rich and poor.

The wealthy work remotely and flee to resorts or pastoral second homes, while the urban poor are packed into small apartments and compelled to keep showing up to work.

As a medievalist, I’ve seen a version of this story before.

Following the 1348 Black Death in Italy, the Italian writer Giovanni Boccaccio wrote a collection of 100 novellas titled, “The Decameron.” These stories, though fictional, give us a window into medieval life during the Black Death – and how some of the same fissures opened up between the rich and the poor. Cultural historians today see “The Decameron” as an invaluable source of information on everyday life in 14th-century Italy.

Boccaccio was born in 1313 as the illegitimate son of a Florentine banker. A product of the middle class, he wrote, in “The Decameron,” stories about merchants and servants. This was unusual for his time, as medieval literature tended to focus on the lives of the nobility.

waterhouse decameron“The Decameron” begins with a gripping, graphic description of the Black Death, which was so virulent that a person who contracted it would die within four to seven days. Between 1347 and 1351, it killed between 40% and 50% of Europe’s population. Some of Boccaccio’s own family members died.

In this opening section, Boccaccio describes the rich secluding themselves at home, where they enjoy quality wines and provisions, music and other entertainment. The very wealthiest – whom Boccaccio describes as “ruthless” – deserted their neighborhoods altogether, retreating to comfortable estates in the countryside, “as though the plague was meant to harry only those remaining within their city walls.”

Meanwhile, the middle class or poor, forced to stay at home, “caught the plague by the thousand right there in their own neighborhood, day after day” and swiftly passed away. Servants dutifully attended to the sick in wealthy households, often succumbing to the illness themselves. Many, unable to leave Florence and convinced of their imminent death, decided to simply drink and party away their final days in nihilistic revelries, while in rural areas, laborers died “like brute beasts rather than human beings; night and day, with never a doctor to attend them.”

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Josse Lieferinxe’s ‘Saint Sebastian Interceding for the Plague Stricken’ (c. 1498). Credit: Wikimedia Commons

After the bleak description of the plague, Boccaccio shifts to the 100 stories. They’re narrated by 10 nobles who have fled the pallor of death hanging over Florence to luxuriate in amply stocked country mansions. From there, they tell their tales.

One key issue in “The Decameron” is how wealth and advantage can impair people’s abilities to empathize with the hardships of others. Boccaccio begins the forward with the proverb, “It is inherently human to show pity to those who are afflicted.” Yet in many of the tales he goes on to present characters who are sharply indifferent to the pain of others, blinded by their own drives and ambition.

In one fantasy story, a dead man returns from hell every Friday and ritually slaughters the same woman who had rejected him when he was alive. In another, a widow fends off a leering priest by tricking him into sleeping with her maid. In a third, the narrator praises a character for his undying loyalty to his friend when, in fact, he has profoundly betrayed that friend over many years.

Humans, Boccaccio seems to be saying, can think of themselves as upstanding and moral – but unawares, they may show indifference to others. We see this in the 10 storytellers themselves: They make a pact to live virtuously in their well-appointed retreats. Yet while they pamper themselves, they indulge in some stories that illustrate brutality, betrayal and exploitation.

Boccaccio wanted to challenge his readers, and make them think about their responsibilities to others. “The Decameron” raises the questions: How do the rich relate to the poor during times of widespread suffering? What is the value of a life?

In our own pandemic, with millions unemployed due to a virus that has killed thousands, these issues are strikingly relevant.

Kathryn McKinley is a professor of English at the University of Maryland. Her research and teaching interests include Chaucer; Ovid, Boccaccio, and late medieval vernacularity; medieval visual literacy and material culture; and the history of later medieval European and English food culture, food scarcity, and famine. She has published in such journals as The Chaucer Review, Viator, and English Manuscript Studies 1100-1700. 

A version of this article was originally published at the Conversation and has been republished here with permission. The Conversation can be found on Twitter @ConversationUS

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Disaster interrupted: Which farming system better preserves insect populations: Organic or conventional?

A three-year run of fragmentary Armageddon-like studies had primed the journalism pumps and settled the media framing about the future of the global insect population: modern agriculture was steering us toward catastrophe.

But scientists remained queasy about what they increasingly came to believe was a simplistic narrative. None of the studies reaching ‘disaster conclusions’ was comprehensive. All were steeped in assumptions that could radically skew the data. Most of the world’s insect population centers were not even studied. And the declines were far from uniform. In some localities, there were reports of increases in overall insect population, and some types of insects are increasing in abundance across the world.

[Editor’s note: This is part two of a two-part series examining the “Insect Armageddon” narrative. Read part one, Are we facing an ‘Insect Apocalypse’ caused by ‘intensive, industrial’ farming and agricultural chemicals? The media say yes; Science says ‘no]

Which brings us to the 2020 meta-study of 166 long-term surveys by Roel van Klink at the German Center for Integrative Biology and his team of 30 scientists. For the first time, scientists had a full platter of studies, covering much of the world. Here was data that might answer questions that by now had turned highly ideological.

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Roel van Klink

The few journalists who picked up on the study’s release noted the finding that insect declines were far less than reported in the smaller-scale studies, and indeed, no catastrophe was imminent. In fact, freshwater insects like mayflies and dragonflies actually have increased over the years, they found, and insect declines in the US, especially in Midwest agricultural areas, began leveling off at the turn of the century.

That doesn’t mean there isn’t a real and significant problem, as van Klink took pains to point out—he called the situation “awfully alarming.” But the difference between a “hair on fire” apocalypse and a serious problem is that there is time to get a better understanding of the causes and, hopefully, make rational decisions to constructively address them.

And it was precisely on the question of causation that the new study fundamentally challenged the “accepted narrative” that modern agriculture and the overuse of pesticides are driving the observed declines.

Effects of modern agriculture

Van Klink’s finding that “crop cover,” which is the phrase he uses to describe farmland, is correlated with increases in insect populations runs directly contrary to the speculations—more often than not presented as fact—that modern farming, especially the use of GMOs and pesticides, is the problem.

The second bugaboo, climate change, also didn’t appear on the suspect list; there was simply no correlation, positive or negative. The primary driver was urbanization, most likely due to the destruction of natural habitat as swamps are drained, rivers channelized, woodlands cleared and land is paved over for housing developments, roadways and shopping malls.

We found moderate evidence for a negative relationship between terrestrial insect abundance trends and landscape-scale urbanization, potentially explained by habitat loss and light and/or chemical pollution associated with urbanization. By contrast, insect abundance trends were positively associated with crop cover at the local (but not landscape) scale in both realms. Specifically, in the terrestrial realm, temporal trends became less negative with increasing crop cover …

Of course, the positive association between agriculture and insect population increases applies to existing fields, not forest or natural grassland cleared for cultivation. As van Klink has pointed out in interviews, the conversion of land to accommodate more farming would also destroy habitat.

But that is exactly the point if sustainability is the key: using technology to boost yields on existing cropland—growing more food on less land—is the most important action we can take to protect habitat and biodiversity.

And that’s what’s been happening. In a 2013 paper titled “Peak Farmland and the Prospect for Land Sparing,” three scholars at Rockefeller University calculated that global increases in crop yields as the result of advanced technologies, including genetic engineering, meant it took about one-third the amount of land in 2010 to grow the same amount of food as in 1961.

The graphs below, taken from the paper, highlight an event that has since been replicated around the world: after World War II total agricultural production, which until then had been largely circumscribed by the amount of land under cultivation, began a steep ascent as farming entered the modern era.

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[To see this process unfold in time, check out the animated charts on crop yields at Our World in Data.]

The boom happened almost simultaneously across the world, from rice in China to wheat in France and Egypt.

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The spur for these dramatic productivity gains is no mystery. After World War II, many of the key agricultural inputs—particularly modern pesticides, synthetic fertilizers, and advanced hybrid crops—came online in a major way. The rise accelerated with the advent of the Green Revolution in the early 1960s, and began to be widely dispersed around the world, rescuing  many countries, such as India, from the brink of mass starvation.

It is this unprecedented historic decoupling of production from land—what has become known as intensive agriculture—that so many in the environmental movement demonize and seek to reverse. One of their central claims: intensive farming is the primary culprit driving biodiversity loss and insect declines.

Yet, a careful look at the data shows the narrative touting small-scale organic-focused farming as a necessary alternative is outdated, even reactionary, writes Ted Nordhaus at the Breakthrough Institute:

Low-productivity food systems have devastating impacts on the environment. As much as three-quarters of all deforestation globally occurred prior to the Industrial Revolution, almost entirely due to two related uses, clearing land for agriculture and using wood for energy.

… attempting to feed a world of seven-going-on-nine billion people with a preindustrial food system would almost certainly result in a massive expansion of human impacts through accelerated conversion of forests, grasslands, and other habitat to cropland and pasture.

… we need to accelerate the long-term processes of growing more food on less land. … raising yields while reducing environmental impacts will require that we farm with ever-greater precision. Raising yields through greater application of technology has often meant more pesticides, fertilizer, and water. But as technology has improved, these trends have begun to reverse.

The organic deficit

The charm of farmer’s markets, Nordhaus writes, is not enough to abandon a system that is limiting land use to counter the effects of urbanization and driving down chemical toxicity levels. It should be noted that organic farming yields on average 10-40 percent less than non-GMO farming, which in turn is about 15 percent less productive than farms using advanced biotechnology. A recent study by the organic advocacy group IDDRI found that if Europe were to adopt agroecological food production practices, productivity would decrease by an average of 35 percent—meaning 35 percent more organic-cultivated land would be needed to produce the same amount of food as produced conventionally.

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Organic agriculture uses more land than no-till intensive agriculture, seen here. Credit: Shutterstock

The math of land saving through the use of modern technologies is so compelling and the yield deficits of organic production so thoroughly cataloged that they can’t be gainsaid. Anti-technology advocates generally prefer to avoid the topic altogether, focusing instead on Goulson-style claims about the adverse effects of chemical pesticides and ignoring organic farmers’ reliance on mechanical plowing using carbon-belching equipment as a form of weed control, which is massively destructive to soil health and biodiversity, and is a major contributor to carbon pollution.

The major sustainability contribution of conventional agriculture is the advent of no-till farming, which began with the use of chemical herbicides like atrazine and accelerated with the debut in 1996 of herbicide-tolerant GMO crops tied to glyphosate. GMO no-till farming has resulted in a massive reduction in carbon release estimated at 37 percent by the Belgian research institute VIB.

The turn away from efficient, intensive agriculture to accommodate the ideological fashion of our times could be a disaster for the fragile insect population. Population growth and growing affluence in the developing world over coming decades will require a sharp increase in necessary food calories, which can only occur by expanding farmable acreage—or by increasing yields on currently available acres.

All of these facts make the German meta-study very uncomfortable for organic farming advocates. The correlation in insect population increases with crops challenges the widespread damage to biodiversity they have been claiming. That may be why most of the major media reporting on the study, such as the BBC, simply ignored the finding, while others—Guardian, Reuters, Smithsonian—included swipes at pesticides not raised by the study authors and written in such a way that the average reader would assume it was backed up by research.

How fast is the decline? How real is the decline?

Trying to determine a global rate of decline, when the data is so uneven and, as the authors say, almost all effects are local and variations are so high even among adjacent sites, is fraught with difficulty. Nevertheless, the new study pins the rate of decline of land-based insects at just under one percent annually, which translates to an 8.3 percent decline per decade.

The study authors note some questions about the scope of the global decline, explaining that it was heavily influenced by what they term “outlier” studies with anomalously high findings. If these outliers are excluded, they say, insect populations would decline by far less, about 15 percent over 25 years.

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This too is not good, but it’s not an apocalypse; and there is time to turn things around even if the estimated trends are accurate. That hopeful take is actually supported by another important, though largely ignored, finding in the study, which is that the terrestrial insect declines in North America were no longer negative after 2000 and freshwater insects increased dramatically.

The fact that North American trends began plateauing or improving around 20 years ago suggests we are headed in the right direction in what had been up until then, according to the authors, the worst performing part of the world. Statistically speaking, once North American data was excluded, the study states that there was only “weak evidence for a negative mean tend” in global populations.

Geography and models

We all naturally gravitate to the headline numbers coming out of these studies. They’re simple, easy to remember and give us a sense of concreteness. Unfortunately, they are probably the least reliable and meaningful findings of all. If the ongoing COVID-19 pandemic has taught us anything, it’s that we should understand complex statistical modelling for what it is: a hypothesis generator or a sophisticated “best guess,” given current knowledge that may, as more facts come to light, prove to be anything from fairly close to wildly off the mark.

All one has to do is look at the maps of the geographic distribution of the studies included in van Klink’s analysis to realize just how problematic any conclusion about global trends is, considering the lack of data from most of the world. The vast majority of studies came from North America and Europe (by my count, almost 2/3 of all the studies).

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There is a total of two studies from all of Africa, relatively few from Asia, and none at all from South Asia (India, Pakistan and Bangladesh). There is a single study from the Amazon, one of the richest sources of insect life on the planet.

These gaps are magnified by the fact that most of these studies concern only one specific order or family of insect, or some other sub-division (e.g. parasitoid wasps). But we know that different insect species vary enormously in their response to changes in climate, weather, disease, pollution and habitat destruction. It simply isn’t plausible that a model can compensate for what is, unfortunately, a massive quantity of unknowns, including, to borrow a phrase, many unknown unknowns, when it comes to insect population trends. Simply said, the likelihood of sampling error is immense.

It should be emphasized that none of this is to take away from the prodigious work of the van Klink research team. Almost all the criticisms outlined here are acknowledged and discussed by the authors themselves.

One of the most refreshing aspects of this study, in fact, has been the humility with which this team, which has done some of the best and most thorough work yet trying to establish global insect trends, has presented their results. In an article accompanying the study in Science, addressed to researchers not associated with the project, the team points the way forward for others in this field, and indeed in any scientific endeavor.

Advances in our knowledge about ongoing biodiversity changes and ability to predict future ones will require the incorporation of layers of nuance in patterns of change and drivers of that change.

The temptation to draw overly simple and sensational conclusions is understand­able, because it captures the attention of the public and can potentially catalyze much needed action in policy development and research arenas. However, fear-based mes­sages often backfire. This strategy has the grave risk of undermining trust in science and can lead to denialism, fatigue, and apa­thy. Embracing nuance allows us to balance accurate reporting of worrying losses with hopeful examples of wins. Hope is a more powerful engine of change than fear.

Jon Entine is Executive Director of the Genetic Literacy Project and a life-long journalist with 20 major journalism awards. Follow him on Twitter @JonEntine

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