The LNT Model

This 4-minute youtube video [https://www.youtube.com/watch?v=T3IwCjWytiA] is excellent. Very clear, lucid, crisp and brief — just what the busy scientist wants. The bottom line is that the Linear Non-Threshold (LNT) Model is not founded on scientific facts. Instead, wherever possible, we should base all governmental policies on scientific, evolutionary-based data.

Let’s hope that powerful leaders in the U.S. EPA, and other regulatory agencies are listening. ☹

—DwN

Dan,

Please watch this 4-minute video summary by John Cardarelli (President, Health Physics Society) on the LNT story. It is impressive and should be shared widely. Most people are more prone to watch a short (but powerful) conceptual summary than delving into many dozens or hundreds of pages of text, describing this fraud…

Ed Calabrese

[I always open “CC” (closed captions), if it’s available, to help me understand what speakers are saying.]

To refresh everyone’s memory about the “LNT Model,” recall that GEITP has discussed this topic at least a half-dozen times. Ed Calabrese, emeritus in environmental health sciences at University of Massachusetts Amherst, has authored and coauthored more than two dozen papers — starting about 2011 — on questioning the scientific conclusions of the fruit fly experiments leading up to the infamous Linear Non-Threshold (LNT) Model for risk assessment (originally) for ionizing radiation exposure. The LNT Model arose from the 1946 Nobel Prize awarded to Hermann Mueller — and was adopted by the U.S. Environmental Protection Agency (EPA) and many other agencies. And, by extrapolation from ionizing radiation, it was proposed that this same model likely holds true for most (if not all) chemical toxicants and carcinogens.

In his Nobel Prize Lecture on December 12, 1946, Hermann J. Muller argued that the dose-response for ionizing radiation-induced germ cell mutations was linear and that there was “no escape from the conclusion that there is no threshold.” However, a recently discovered (by Calabrese in 2015) commentary by Robert L. Brent indicated that Curt Stern, after reading a draft of part of Muller’s Nobel Prize Lecture, telephoned Muller — strongly advising him to remove reference to the flawed linear non-threshold (LNT)-supportive Ray-Chaudhuri findings and strongly encouraged him to be guided by the threshold supportive data of Ernst Caspari [who, incidentally, was DwN’s genetics mentor in college]. Brent wrote that Mueller refused to follow Stern’s advice, thereby proclaiming (during his Nobel Prize Lecture) support for the LNT dose-response, while withholding evidence that was contrary. This finding is of historical importance, because Muller’s Nobel Prize Lecture then gained considerable international attention in 1946 and was a turning point in acceptance of the linearity model for radiation and chemical hereditary and carcinogen risk assessment.

Ed asserts that the science used — to support the LNT model adopted by the NAS’s 1956 Biological Effects of Atomic Radiation (BEAR) I Genetics Panel — was also tainted by its leaders, who he says deliberately refused to include evidence from NAS’s own Atomic Bomb Casualty Commission (ABCC) human genetic study, also known as the Neel and Schull 1956a report.

Calabrese says Neel and Schull showed “an absence of genetic damage in offspring of atomic bomb survivors, which supports a threshold model (i.e. not the LNT model),” but this was not considered for evaluation by the genetics panel, “therefore, those data could not figure into its decision to recommend the erroneous LNT dose-response model for risk assessment.”

Calabrese suggests that the panel’s work was undermined by Hermann J. Muller and BEAR I chairman Warren Weaver, who “feared that human genetic studies would expose the limitations of extrapolating from animal, especially the fruit fly, Drosophila, to human responses, and admitting this would strongly shift research investments/academic grants from animal to human studies.”

Calabrese adds, “The country expects its scientists to be honest and to follow real data. The BEAR 1 Genetics Panel failed on both counts, being loyal only to their ideology, and then hiding it. They were hailed by many media outlets as the Genetics Dream Team — giving them ‘further cover’ so that their deceptions would never be known. They have gotten away with it, so far, for 68 years.” How much longer will we believe that “inaccurate scientific conclusions do not lead to bad government policy” — which continues to be practiced, today…??

“This history should represent a profound embarrassment to the U.S. NAS, regulatory agencies worldwide — and especially to the U.S. EPA and the risk-assessment community — whose founding principles were so ideologically determined and accepted with little, if any, critical reflection.”

DwN

Number of the Week: “100,000 times greater (than background).” According to Ed Calabrese, Hermann Mueller knew of Caspari’s University of Rochester study — before he gave his Nobel talk in December 1946.

“That [fruit fly] study had shown that at the ‘low’ chronic radiation dose rate (i.e., yet still about 100,000 times greater than background), no radiation-induced mutation effects were found. The Caspari study supported the threshold model, and not the LNT model.”
—DwN

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Genome evolution and divergence in cis-regulatory architecture is associated with condition-responsive development in horned dung beetles

This topic is “a first for GEITP” (!!) : studying developmental evolution in the dung beetle. In our 16 years of existence, GEITP is certain that we’ve never discussed gene regulation in the dung beetle before…!! ☹

This is a horned dung beetle, they are known to be the strongest insect in the world, They Can Lift 200-1141 Times Their Own Body Weight. These Insects Tend to be 0.75

But, even the genomes of beetles can “sense” environmental pressures (signals such as nutrition from food), and then, downstream, genetic networks are altered in order to produce morphological changes (e.g., size and shape of head horns) that will make the animal more likely to survive (e.g., success in fighting off other males before breeding) in its changing environment.

Recall that epigenetic regulation of genes includes DNA methylation, RNA-interference, histone modifications and chromatin-remodeling. This study involves histone-marking and chromatin-remodeling — inferred by DNA sequence differences in regions of the genome responsible for the horn morphology phenotype of these beetles. ☹

Phenotypic plasticity is thought to be an important driver of diversification and adaptation to environmental variation, yet the genomic mechanisms mediating plastic trait development and evolution remain poorly understood. The Scarabaeinae, or true dung beetles, are a species-rich clade of insects recognized for their highly diversified nutrition-responsive development — including that of cephalic horns (horns on the head) — which are evolutionarily novel, secondary sexual weapons that exhibit remarkable intra- and inter-specific variation. Authors [see attached] investigated the evolutionary ”basis for horns,” as well as other key dung-beetle traits, via comparative genomic and developmental assays.

Phenotypic plasticity is defined as “the capacity of a single genotype to produce multiple phenotypes in response to environmental variation” and constitutes a ubiquitous property of multicellular life. Plasticity is thought to be an important driver of adaptation — allowing organisms to maintain high fitness in the face of environmental adversity and variability, as well as of diversification via evolutionary changes in the genetic architectures underlying plastic trait formation.

The ecological and evolutionary significance of phenotypic plasticity has received much attention, and diverse genes and signal transduction pathways have been identified as important mediators of plastic development across biological systems. In addition to coding sequence, epigenetic modifications such as histone marking are predicted to provide important mechanisms of plastic gene expression regulation. Furthermore, recent quantitative trait locus (QTL) analysis, combined with genome editing by CRISPR-Cas9, has begun to establish first causal connections between several cis-regulatory elements and the plastic development of nematode feeding structures. Yet, despite these advances, the genomic basis underlying developmental plasticity and its evolution, and in particular the role of the non-coding genome and chromatin architecture in regulating conditional responses in trait formation, remain largely unknown.

One group of animals that exhibit an extreme degree of phenotypic plasticity are the true dung beetles (Scarabaeinae) (yes, it’s spelled correctly ), a very diverse clade (>6,000 extant species) found on every continent except Antarctica. The extraordinary evolutionary success of this group is attributable at least in part to their ability to exploit an abundant resource inaccessible to most other insects — i.e., dung. For nearly every species, the acquisition and utilization of dung is essential to each aspect of these beetles’ life history. This includes not only consuming dung as a food source (coprophagy), but also as a resource for larval food provisioning and nest construction, thereby enabling a single offspring to complete development from egg to adult, within the confines of an underground brood-ball.

One key adaptation aiding in this strategy is a highly diversified degree of nutrition-responsive (plastic) development. In the case of dung beetles, nutrition-responsive development is a flexible developmental response to variable and limited larval food quality and quantity — resulting in a wide range of adult body sizes, which in turn has fueled the evolution of alternative, body size-dependent morphological, physiological, and behavioral phenotypes. Accordingly, phenotypic plasticity is predicted to be an evolutionary driver for many dung beetle adaptations.

Furthermore — due to their diversity, abundance, pronounced environment-sensitive development, and unique feeding and reproductive traits — dung beetles have thus long served as important models for behavioral (e.g., status-dependent selection and sperm competition models), developmental (e.g., mechanisms of plasticity), evolutionary (e.g., the origins of evolutionary novelties), and ecological studies (e.g., meta-population theory, nutrient recycling, soil aeration). However, despite the significance of dung beetles in both basic and applied science, a reference-quality genomic resource for any member of this insect group has so far been lacking.

Among the most conspicuous morphological trait of dung beetles are head horns — novel, highly diversified secondary sexual weapons used in reproductive competition. Horns vary tremendously in shape, size, and number across and within species, mediate widespread sexual dimorphisms, and exhibit a high degree of nutrition-responsive development among conspecific males (i.e., animals within the same species). Most commonly, horn development is limited to, and often exaggerated, in males whereas females are (usually) hornless.

Intriguingly, head horns lack homology to any other appendage or body part among Insecta, and as such qualify as an evolutionary novelty even by the strictest of definitions — yet gains, losses, and modifications to horn structure are common among even closely related species. Thus, beetle horns exhibit a high degree of evolutionary lability and represent a powerful natural system for understanding how complex traits originate and diversify.

This study began by presenting

chromosome-level genome assemblies of three dung beetle species in the tribe Onthophagini (>2500 extant species) — including Onthophagus taurus, O. sagittarius, and Digitonthophagus gazella. Comparing these assemblies (to those of seven other species across the order Coleoptera) identified evolutionary changes in coding sequence associated with metabolic regulation of plasticity and metamorphosis. Authors then contrasted chromatin accessibility in developing head horn tissues of high- and low-nutrition O. taurus males and females and identified distinct cis-regulatory architectures underlying nutrition — compared to sex-responsive development, including a large proportion of recently evolved regulatory elements sensitive to horn morphology determination.

Binding motifs of known, and new candidate, transcription factors were identified and are enriched in these nutrition-responsive open chromatin regions. This study highlights the importance of chromatin-state regulation in mediating the development and evolution of plastic traits, demonstrates that gene networks are highly evolvable transducers of environmental and genetic signals, and provides new reference-quality genomes for three species that will strengthen future developmental, ecological, and evolutionary studies of this insect group.
DwN
PLoS Genet March 2024; 20: e1011165
COMMENT:
Christine has sent GEITP a <> about this topic of the dung beetle. But — how many GEITPers will “understand” this joke…?? How many of us have read fictional novels written by Franz Kafka (1993-1924)…??

“I feel a metamorphosis coming on…”
F. Kafka ☹

Answer to my question above: Franz Kafka’s message in his short novel, The Metamorphosis, deals with modernist themes — such as isolation and the absurdity of life. In the story, the main character, Gregor, has devoted himself to his family. And the absurd situation of becoming an insect has left Gregor alienated from other humans…

DwN

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The NIH Sacrifices Scientific Rigor for DEI

Pasted below is an excellent brief article/letter — on a topic that is mostly forbidden to discuss (i.e., that the government “is sacrificing its highest standards of scientific creativity” in order to fully embrace DEI). I’ve had experiences and have heard of other stories in which “scientific rigor” has simply been muzzled, or discouraged, in order to promote this “Woke” ideology of “Diversity, Equity, and Inclusion” (DEI). Recently — some States, and some universities and companies, in the U.S. have begun to reign in this political nonsense; so, perhaps this fad is on its way out. [Let’s hope “mandatory usage of pronouns” is the next issue to get phased out.]

For any GEITP’er(s) not aware of this partisan ideology, congratulations for remaining naïve. D.E.I. represent organizational frameworks which seek to promote “fair treatment and full participation of all people,” particularly groups “who historically have been underrepresented or subject to discrimination — on the basis of identity or disability.” E.S.G. stands for environmental, social, and governance. D.E.I. are regarded as pillars in ESG frameworks and represent the three main topic areas in which companies and academia are expected to report. DEI comprises the central “S” in “ESG”. It is proposed that “there can be no successful ESG without a sharpened focus on DEI.”

DwN

The NIH Sacrifices Scientific Rigor for DEI
“Diversity, equity, and inclusion” (DEI) in medical programs? It is not surprising, nor is it the first time grant money has been allocated for the purpose of furthering this discriminatory ideology.

John D. Sailer of the National Association of Scholars acquired thousands of pages of documents, revealing “how the [National Institutes of Health (NIH)] enforces an ideological agenda, prompting universities and medical schools to vet potential biomedical scientists for ‘wrongthink,’ regarding diversity.” The NIH has long been known to support DEI, and require the schools it funds to hire for diversity. Cornell University is just the latest to take the grant money from the NIH and join the ranks of the DEI-cluster hiring cadre.

Sailer has reported on NIH grants before. The NIH’s Faculty Institutional Recruitment for Sustainable Transformation (FIRST) program, “which funds diversity-focused faculty hiring in the biomedical sciences,” has already funded institutions like the University of South Carolina and the University of New Mexico. By accepting FIRST grant money, colleges, universities, and medical schools must use diversity statements for all grant faculty hires. If candidates do not demonstrate sufficient devotion to DEI based on rubrics, they receive a low score—and typically will not be hired, Sailer explains,

That rubric penalizes job candidates for espousing colorblind equality and gives low scores to those who say they intend to ‘treat everyone the same.’ It likewise docks candidates who express skepticism about the practice of dividing students and faculty into racially segregated ‘affinity groups.’

Additionally, the FIRST rubrics often value DEI commitment on par with merit and academic excellence. The consideration given to DEI may vary depending on the rubric—like the Florida State University faculty hiring rubric which weighs DEI commitment at 28 percent—but it is a key factor regardless. Requiring a quota of diversity hires without respect to merit, especially in the medical field, is an alarming trend — not only because schools will be churning out students who could have a deficiency of proper training, but also for ideological discrimination against faculty. Sailer’s records requests show the truth behind DEI-hiring,

The records underscore that scientists simply can’t get hired in the program without an outstanding DEI score. Northwestern’s grant progress report describes an evaluation rubric that equally weighs a ‘commitment to diversity’ and research potential—a remarkable value judgment for a program that is supposed to be focused on cancer, cardiovascular health, and neuroscience.

The FIRST grant program sets a dangerous precedent. Even some colleges and universities who have not received FIRST grants are utilizing DEI-rubrics in hiring decisions—their motivations for doing so are not always disclosed, but it usually comes down to status, seeking future funding, or sheer commitment to the DEI ideology.

From administrative bloat to DEI-cluster hiring and merit-blind admissions quotas, when will this madness end? States like Texas, Utah, and Florida are already pushing back against DEI initiatives. However, with funding pouring into both red and blue states from institutions like the NIH, defeating the DEI hydra remains challenging. Texas, for instance, has banned DEI statements and offices at state universities, yet two universities have secured NIH FIRST grants and vow to promote DEI. The ensuing legal and legislative fights will be intriguing to watch.

As concerns and tensions around DEI continue to mount, spurred by revealing documents, investigations, and increasing pressure on colleges and universities to be accountable for their actions—or lack thereof—what will it take to vanquish the DEI beast? While we await that decisive moment, we remain steadfast in our commitment to uphold truth, excellence, and integrity in higher education.

Until next week.
Kali Jerrard
Communications Associate
National Association of Scholars

COMMENTS:
Dear Dr. Nebert,
While I understand there can be different views on some of these issues, but to imply in the title that NIH plans to sacrifice scientific rigor for DEI is simply “over the top”. It is not an “either or,” the FIRST program promotes “both and.” In the end, without successful role models that reflect our growing diverse population as doctors, research scientists, engineers, and other biomedical professionals — we simply continue to propagate the myth that only white men are worthy of such professions. I, for one, would like to break down some of those barriers, and if it means incentivize some opportunities, then I am all for it.
Sincerely, Ken Greis, PhD

Hi Dan:
“Incentivize some opportunities,” says Ken Greis. I guess lower standards for admission, and eliminating or reducing metrics for completion of training (PhD, MD, commercial pilot license. or whatever) — are various means “to incentivize.” The elimination of meritocracy is a bad idea and we will suffer the consequences for generations. We already have in place programs to assist individuals from underrepresented groups. If we are really serious about enhancing the chances for these individuals to achieve their goals, the solution is not “lowering the bar” but rather “raising the ground on which they stand” so that the bar can be more easily cleared.

I’ve been a standing member of three NIH study sections, as well as serving ad hoc on over 40 others. In addition, I served as PI for a T35 training grant from NIEHS offering summer internships for minority undergraduates. We recruited African-American students from Xavier in New Orleans. I also directed a T32 training grant for a dozen years, and we actively recruited persons of color — which was difficult, given the demographics in Oregon. In my 35 years in academia, I saw many programs designed to enhance opportunities for minority students and never saw any barriers. I find the statement “..continue to propagate the myth that only white men are worthy of such professions” very offensive.

Dr. Greis is obviously well meaning, and I have no doubt he sincerely wants to increase the representation of underserved populations in these professions. As is typical though, rather than an honest discussion of your “alternative facts,” he simply requests that you cut off further communication.

Keep up the good work, Dan.

David E. Williams
Extinguished Professor Emeritus
Linus Pauling Institute and Environmental and Molecular Toxicology; Oregon State University

P.S. And, of course, Victor Davis Hanson captures what I was trying to say — in a much more elegant fashion: ☹☹

“If one does not qualify for a position or slot by accepted standards, then a series of further remedial interventions are needed to sustain the woke project — by providing exceptions and exemptions, changing rules and requirements, and misleading the nation that a more “diverse” math, or more “inclusive” engineering, or more “equity” in chemistry can supplant mastery of critical knowledge that transcends gender, race, or ideology…”

March 27, 2024

So, if I understand Ken Greis correctly, “justification” comes from the need to create role models. I am not sure that role models need to be of the same race or sex. As a youth, I came from a low middle class Italian-American catholic family. It was my impression that important professions were dominated by white Anglo-Saxon protestants. I didn’t have a problem with that. In fact, I embraced them as role models.
Ray
Professor Emeritus, Proctor & Gamble; University of Massachusetts at Amherst

Dear Dr. Nebert,
While I understand there can be different views on some of these issues, but to imply in the title that NIH plans to sacrifice scientific rigor for DEI is simply “over the top”. It is not an “either or,” the FIRST program promotes “both and.” In the end, without successful role models that reflect our growing diverse population as doctors, research scientists, engineers, and other biomedical professionals — we simply continue to propagate the myth that only white men are worthy of such professions. I, for one, would like to break down some of those barriers, and if it means incentivize some opportunities, then I am all for it.
Sincerely,
Ken Greis, PhD
Professor of Cancer Biology; Univ Cinci College of Medicine

Hi Dan,

I am a member of National Association of Scholars (NAS). It will be interesting to see if you get any pushback on this NAS Op-Ed article.
I hope you are well.
Nancy

Professor Emerita, Oregon State University

No wonder that in Latin, “DEI” is the plural of DEUS, god: “The gods.”

Alvaro

Professor Emeritus, Univ Cincinnati College of Medicine

From: Anonymous
Sent: Friday, March 22, 2024 5:36 PM
Dan,
I saw this in a Letter-to-the-Editor, Wall Street Journal:
What “DEI” really means:
“D” for Divisiveness

“E” for Entitlement

“I” for Intimidation

—————
—Professor. [Somewhere] Not retired…

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Scientists Find ‘Switch’ That Stops Immune System Attacking Healthy Cells

GEITP believes that this finding might represent a significant, HUGE breakthrough in the field of autoimmune diseases. (??)

DwN

Scientists Find ‘Switch’ That Stops Immune System Attacking Healthy Cells

20 March 2024

By DAVID NIELD

Antibody system

Illustration of antibodies attacking virus particles.

Our immune system is talented at telling the difference between the chemistry of our own body and that of an invading pathogen. When it malfunctions, our body can become host to an intense civil war.

Scientists are keen to understand this in more detail, and a newly identified ‘switch’ that deactivates a sensor of foreign DNA may provide important insight.

A key part of this discovery, made by a team from the Swiss Federal Institute of Technology Lausanne, is an enzyme called cyclic GMP-AMP synthase (cGAS).

This protein is tasked with identifying infiltrating viruses. It binds to any foreign DNA floating out of place in a cell’s gooey cytoplasm and triggers a reaction alerting the body to an invader.

We already know that cGAS needs to be tightly regulated to keep it in check, especially once it enters a cell’s nucleus. The new study identifies a biological switch that marks the enzyme for deletion in places where no immune response is required.

cGAS illustration

This is the structure of cGAS, with ubiquitin attached. (Xu et al., Nature, 2024)

“Along with previously defined interactions with nucleosomes, our results provide a complete structural model of the nuclear regulation of cGAS,” write the researchers in their published paper.

Scientists have established that as cells divide to grow, the nuclear envelope dissolves, giving cGAS easy access to the DNA bundled within. There, it binds to DNA packaging units called nucleosomes and is covered by a protein called BAF, waiting for when it might be needed.

In this study, via a detailed analysis of cells grown in the lab, the team identified a protein complex named CRL5–SPSB3 (the last acronym, we promise). It adds a chemical called ubiquitin to cGAS to mark it as disposable.

This is the key switch that kills off cGAS when it’s not needed – when there’s no threat from foreign DNA. Essentially, it stops the enzyme from attacking healthy cells by gently ushering it out of the picture as these cells grow.

Part of the signaling that controls the immune system response is called the interferon or IFN pathway, and the study shows how both cGAS and CRL5–SPSB3, which are responsible for flicking the switch one way or the other, are involved in IFN.

“These results demonstrate that nuclear cGAS levels affect the cellular IFN tone and reveal a role for CRL5–SPSB3 in cell-intrinsic immunity,” write the researchers.

Autoimmune disorders, such as type 1 diabetes and inflammatory bowel disease, happen when immune system controls don’t function as they should. The new research highlights one of those controls as worth studying further.

Now that we know more about how cGAS works, we might be able to develop effective ways of ensuring it’s always well-behaved.

“Our research defines protein degradation as a determinant of cGAS regulation in the nucleus and provides structural insights into an element of cGAS that is amenable to therapeutic exploitation,” write the researchers.

The research has been published in Nature.

COMMENTS:

Sent: Saturday, March 23, 2024 12:42 PM

This immunology paper in Nature was very interesting. But overhyped, in my opinion.
Nancy

I must agree with Nancy — everything in immunology is over-hyped, mainly because: 1) it’s complicated; 2) immunologic diseases are VERY common; and 3) we have no good treatments for any of them. ☹
Walt

The cGas-STING pathway is the main innate immune response in the settings of infection, intracellular stress, and tissue damage — including detection of misplaced DNA (either host- or pathogen-derived) in certain cell types. Therefore, I believe the Nature paper is of great interest. There are known specific inhibitors of the cGas-STING pathway.
Divaker

Sent: Saturday, March 23, 2024 6:24 AM

In my opinion, this finding is very important and very much needed.
Ray

Professor Emeritus,

For anyone interested in learning more about this topic, please see this 2021 review [attached] in Nature Reviews Immunology, titled “The cGAS–STING pathway as a therapeutic target in inflammatory diseases.” This review has been out 3 years now and has more than 800 citations already(!!)…

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A HORRIFIC STORY OF DISHONESTY IN PUBLISHING SCIENTIFIC PAPERS

COMMENTS

 

Hi Dan, I see that China is also trying to tackle the predatory journals and fake articles!

Olavi
China updates naughty list of journals

China has updated its Early Warning Journal List — a list of journals that are deemed to be untrustworthy, predatory or not serving the Chinese research community’s interests. The latest edition includes 24 journals and, for the first time, takes note of misconduct called citation manipulation, in which authors try to inflate their citation counts. Scholarly literature researcher Yang Liying heads up the team that produces the influential list and spoke to Nature about how it’s done.

Here is an interesting alert from Nature Briefing—on the same theme, or topic, as your recent blog!

Olavi
Co-authors point the way to paper mills

A new approach looks at authors, rather than the content of papers, to help identify journal articles that originate from ‘paper mills’ — factories for fake research. It looks for unusual patterns of co-authorship and peculiar networks of researchers, which could be a sign that authorship was paid for, rather than earned. The approach could be crucial as artificial intelligence (AI) systems make it all too easy to churn out convincing fake manuscripts. “This is the kind of signal that is much more difficult to work around, or outcompete, by clever use of generative AI,” says Hylke Koers of the International Association of Scientific, Technical, and Medical Publishers.

Thanks for sharing! As course coordinator for our Advanced Writing in Biology course, we always devote the early part of the course to discussion about scientific misconduct and publishing ethics.

It was interesting that the concept of predatory journals didn’t connect well with students, even though we tried to emphasize that when they moved into writing their literature reviews — they needed to rely on indexed databases (such as PubMed) to find credible papers from credible sources. Too often, they just Google whatever and end up with crap.

This year, our focus was on generative Artificial Intelligence (AI), which just makes the whole problem worse. If ChatGPT can’t find what you need, it just hallucinates and makes it up. These are troubling times for scientists who wish to remain honest!

Chris

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Photoreceptor Evolution–from Water Animals to Land Animals

This topic is among the most obvious of “gene-environment interactions” topics…!! 😊 During evolution, when vertebrates first left the water and ventured onto land, they encountered a visual world that was radically different from that of their aquatic ancestors. In order to survive successfully, “new” land species were required to adapt visually, in terms of being able to find food, avoid predators, and sexually reproduce. “The need to see acutely” — represents the environmental pressure; and necessary (and relatively evolutionarily “quick”) changes in visual networks of the eye (and/or brain) — represents the response by genes…

Fish exploit the strong wavelength-dependent interactions of light with water by differentially sending visual image signals from as many as five spectral photoreceptor types into distinct behavioral programs. However, out of the water — the same spectral rules do not apply, and this adaptation required rapid changes in response to this environmental pressure.

Early tetrapods [e.g., Kenichthys from China ~395 million years ago (MYA), Gogonasus & Panderichthys ~380 MYA, and then salamanders with four legs] soon evolved the double cone, a still poorly understood pair of new photoreceptors that increased the “ancestral terrestrial” complement from five to seven photoreceptors. Subsequent non-mammalian lineages differentially adapted this highly parallelized retinal input strategy for their diverse visual ecologies. In contrast, mammals (first appearing ~225 MYA) shed most of their ancestral photoreceptors and converged on an input strategy that is extraordinarily general. In eutherian mammals (i.e., animals born via placenta), including humans, parallelization emerged gradually during evolution, as the visual signal began to traverse the layers of the retina and onwards, into the brain.

Vertebrate vision first evolved in the water, where (for >50 million years) it was consistently based on visual signals from five anatomically and molecularly distinct types of photoreceptor neurons: rods, as well as ancestral red, green, blue, and UV cones (expressing RH, LWS, RH2, SWS2, and SWS1 opsin, respectively). In the water, these five input streams are probably best thought of as parallel feature channels that deliver distinct types of information to distinct downstream circuits. This is because water absorbs and scatters light in a wavelength-dependent manner (see Fig 1A in attached pdf file), which means that “beyond color,” different spectral photoreceptor channels inherently deliver different types of visual information.

Aquatic visual systems have recently been proposed to evolutionarily reach “answers” that exploit these differences. In this view, photoreceptors represent parallel channels that are differentially wired to drive and/or regulate distinct behavioral programs (see Fig 1B in attached pdf file): First, rods and ancestral red cones are the eyes’ primary brightness sensors; they are used for general-purpose vision and to drive circuits for body stabilization and navigation. Second, ancestral UV cones are used as a specialized foreground system, primarily wired into circuits related to predator–prey interactions and general threat detection. Third, ancestral green and

blue cones probably represent an auxiliary system, tasked with regulating, rather than driving, the primary red/rod and UV circuits.

This ancestral strategy exploits the specific peculiarities of aquatic visual worlds; however, in air the same rules do not necessarily apply. For example, in water, object vision can be a relatively easy task, because background structure tends to be heavily obscured by an approximately homogeneous aquatic backdrop. At short wavelengths, including in the UV range, this effect can be so extreme that no background is visible at all. Many small fish exploit this fact of physics to find their food. Out of water, this and many other “ancestral visual tricks” no longer work, because in air, contrast tends to be largely independent of viewing distance: everything is visible at high contrast. Accordingly, when early would-be tetrapods started to crawl out of the water, strong selection pressures would have favored a functional reorganization of some of these inherited aquatic circuits; nowhere is this more evident that at the level of the photoreceptors themselves.

One of the earliest and perhaps most important retinal circuit changes was the emergence of the double cone, which took the “aquatic ancestral” photoreceptor complement of five to a “terrestrial ancestral” complement of seven (see Fig 1 in attached pdf file). The visual systems of all extant tetrapods, including humans, directly descend from this early “terrestrialized” retinal blueprint. However, from there, different descendant lineages have taken this highly parallelized retinal input strategy and embarked upon radically different visual paths. Most lineages, including those that led to modern-day amphibians, reptiles, and birds — have retained the terrestrialized ancestral blueprint, modifying upon it to suit their unique visual ecologies.

Mammals, however, have ended up on a very different path. Their early synapsid ancestors gradually shifted some of their visual systems’ “heavy lifting” out of the eye and into the brain. Along this path — whether as

cause or consequence — descendant lineages gradually decreased their photoreceptor complements from seven types to six, then five, and eventually to the mere three that we see in eutherians today (see Fig 1C in attached pdf file): Rods (RH), as well as ancestral red (LWS) and UV cones (SWS1).

Primates, including humans, have then taken this eutherian strategy to the extreme: >99.9% of all photoreceptors in our eyes are either rods or ancestral red cones (including both “red-” and “green-shifted LWS variants”), the ancestral “general purpose” system of the eye. The remaining 0.1% is what is left of the ancestral UV system, today expressing a blue-shifted variant of the SWS1 opsin (hence, often called “blue cones,” not to be confused with ancestral blue cones that express SWS2). In concert, the “three” cone variants drive achromatic vision (although with limited contribution from ancestral UV cones), while in opposition they serve color vision.

However, this “textbook strategy” is far removed from the original aquatic circuit design and probably quite unique to our own lineage. Accordingly, for understanding vision in a general sense, and to understand our own visual heritage, it will be critical to respect the vertebrates’ shared evolutionary past. Here, vision is built on a retinal circuit design that begins with major parallelization — right from the original evolutionary input. 😉😊

DwN

PLoS Biol Jan 22: e3002422

Posted in Center for Environmental Genetics | Comments Off on Photoreceptor Evolution–from Water Animals to Land Animals

A HORRIFIC STORY OF DISHONESTY IN PUBLISHING SCIENTIFIC PAPERS

Below are two responses to the Feb 7th GEITP blog email about “companies churning out fake papers are now bribing journal editors; and some editors are agreeing to accept large sums of cash ‘under the table’ to help fraudulent academicians get their ‘fake paper’ published.” ☹

DwN

From: Christine Curran
Sent: Friday, February 9, 2024

Thanks for sharing! As course coordinator for our Advanced Writing in Biology course, we always devote the early part of the course to discussion about scientific misconduct and publishing ethics.

It was interesting that the concept of predatory journals didn’t connect well with students, even though we tried to emphasize that when they moved into writing their literature reviews — they needed to rely on indexed databases (such as PubMed) to find credible papers from credible sources. Too often, they just Google whatever and end up with crap.

This year, our focus was on generative Artificial Intelligence (AI), which just makes the whole problem worse. If ChatGPT can’t find what you need, it just hallucinates and makes it up. These are troubling times for scientists who wish to remain honest!

Chris

Christine Curran, PhD

Professor, Northern Kentucky University, Highland Heights, KY

From: Olavi Pelkonen Sent: Friday, February 9, 2024

Dan,

Here is an interesting alert from Nature Briefing—on the same theme, or topic, as your recent blog!

Olavi
Co-authors point the way to paper mills

A new approach looks at authors, rather than the content of papers, to help identify journal articles that originate from ‘paper mills’ — factories for fake research. It looks for unusual patterns of co-authorship and peculiar networks of researchers, which could be a sign that authorship was paid for, rather than earned. The approach could be crucial as artificial intelligence (AI) systems make it all too easy to churn out convincing fake manuscripts. “This is the kind of signal that is much more difficult to work around, or outcompete, by clever use of generative AI,” says Hylke Koers of the International Association of Scientific, Technical, and Medical Publishers.

Nature | 5 min read

Reference: arXiv preprint

​Olavi Pelkonen

eProfessor of Pharmacology

University of Oulu, Finland

From: Nebert, Daniel (nebertdw)
Sent: Wednesday, February 7, 2024

It was about 2004 that publishing companies began publishing scientific manuscripts online, rather than in paper journals. GEITP is guessing that PLoS Publishing Company was first (and it remains honest and legitimate). But it didn’t take long before somewhat shady, to downright fraudulent, “predatory online open-access journals” began to pop up. By 2014, there were at least 4,500 “predatory journals” and today there are probably more than 18,000.(!!)

Over the past 15 years, GEITP has discussed many of these fraudulent publisher stories (https://genewhisperer.com/). One extreme example was a “family of four, living in a tiny house in a small village in Turkey, using their kitchen table as their ‘publishing company’, and raking in $1.2 million in one year (without paying any taxes).” The modus operandi is always similar: [a] recruit for “papers” (even if they’re only one or two pages in length), [b] pretend they are quickly “peer-reviewed” (which may or may not be the case), [c] accept the manuscript quickly, almost always without any need for modifications, and [d] charge an exorbitant amount of money in “page charges” to have “your manuscript published quickly online.”

One major factor in considering an academic PhD or MD for a position, or promotion to a higher position — is the “number of publications” the applicant reports. [In some circles, the “number of publications only in highly prominent journals” is an important criterion, but that’s not the case for the vast majority of hiring and promoting of individuals in academia, worldwide.]

And then, in 2009, we should all remember the Sokal Hoax [ https://physics.nyu.edu/faculty/sokal/ ] in which a physicist wrote a completely gibberish paper and submitted it to what was considered one of the better journals in the field (Social Text). And the paper supposedly got peer-reviewed and published anyway. The editors later backtracked by saying that they thought the paper “lacked originality, that it wasn’t well written, that they just accepted it as a favor to Dr. Sokal, a physicist, visiting their rigorous area of study, and so on” — but the fact remains that an editor should be able to distinguish a valid paper from a pile of garbled nonsense.

During the last 6-8 years, it has become popular to “tack on the names of coauthors from the same institute or hospital who were not actually involved with the research,” to help these individuals in getting hired and/or promoted (i.e., maybe five scientists did all the work and writing the manuscript — but another 18 physicians, in need of “more publications”, had their names inserted in the middle of the co-authorship list). GEITP has also covered such fraudulent stories in the recent past.

Now comes the latest [see attached Jan 2024 editorial]: shady “companies,” churning out fake papers, have decided to bribe journal editors.(!!) Exploiting the growing pressure on scientists worldwide to amass publications — even if they lack resources to undertake quality research — these sneaky intermediary “companies” (by some accounts) pump out tens, or even hundreds, of thousands of articles every year. Many contain fictional data; others are plagiarized, or of low quality. Regardless, authors pay to have their names on them, and these “paper mills” can make tidy profits.

Nicholas Wise (a fluid dynamics researcher at the University of Cambridge (England), moonlights as a scientific fraud buster; he was digging around on shady Facebook groups and saw something new. Rather than targeting potential authors and reviewers, someone (who calls himself “Jack Ben”, from a firm whose Chinese name translates as “Olive Academic”) was approaching journal editors — and offering them large sums of cash, in return for accepting papers for publication. [Even a spokesperson for Elsevier said every week its editors are offered cash in return for accepting manuscripts.]

“Sure, you will make money from us,” “Ben” promises prospective collaborators in a document linked to the Facebook posts, along with screenshots showing transfers of as much as $20,000 or more. More than 50 journal editors have already signed on, he wrote. There was even an online form for interested editors to fill out.

According to a new preprint, more than half of medical residents in one country admit they have engaged in research misconduct — such as buying papers or fabricating results. One reason is that publications, although no longer always a strict requirement for career advancement, are still the easiest path to promotion in a range of professions — including doctors, nurses, and teachers at vocational schools, according to sources. Yet these groups may have neither the time nor the training to do serious research. In such a setting, paying a few hundred or even a thousand dollars to see one’s name in print may seem a worthwhile investment.

Everyone is invited to read the complete amazing story in the attached pdf file.(!!) 😊

For scientists about to submit their manuscript and who are wondering how to select an honest journal versus a “predatory online open-access journal” — you are encouraged to contact the “Membership in the Directory of Open Access Journals” or the “Open Access Scholarly Publishers Association.” These are good indicators that are able to confirm whether a journal is not predatory. You can check these sites to help you determine that the journal in which you are interested is legitimate. Also, please read this interesting 2020 publication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237319/ and these 2024 updated library guidelines as to “how to determine whether your selected journal is legitimate or predatory”: https://nuim.libguides.com/openaccess/predatory 😊😊

DwN

Science 19 Jan 2024; 383: 252-255

Posted in Center for Environmental Genetics | Comments Off on A HORRIFIC STORY OF DISHONESTY IN PUBLISHING SCIENTIFIC PAPERS

Breaking Through: My Life in Science by Katalin Karikó review – real-life lessons in chemistry

This book might become mandatory reading for some high school or college courses — designed to encourage women to go into science and persist at tenacity and self-belief. 😊😊

DwN

Breaking Through: My Life in Science by Katalin Karikó review – real-life lessons in chemistry

This vivid account of the Hungarian biochemist — who endured decades of derision before pioneering Pfizer’s Covid vaccine — is a tribute to her tenacity and self-belief

Robin McKie
Robin McKie

Sun 11 Feb 2024

In May 2013, Katalin Karikó turned up for work at her laboratory at the University of Pennsylvania and found her belongings piled in the hallway. “There were my binders, my posters, my boxes of test tubes,” she recalls. Nearby a lab technician was shoving things into a trash bin. “My things!” Karikó realised.

Despite having worked at the tiny lab for years, the scientist – then in her 50s – was cast out, without notice, for failing to bring in “sufficient dollars per net square footage”. In short, she had not attracted enough grants to justify the meagre space she occupied.

“That lab is going to be a museum one day,” Karikó hissed at the manager who had ousted her. These were odd but prophetic words, as is made clear in this engrossing, touching tale of the tribulations of a scientist now recognised as one of the world’s greatest biochemists, a woman who helped create the vaccines that saved millions during the Covid-19 pandemic.

Karikó comes from a humble background in central Hungary, growing up in a single-roomed house that was heated in winter by a solitary stove and had no running water. Her father had to work as a labourer when he was dismissed from his job as a master butcher after falling foul of local Communist party officials.

It was a harsh life but a loving one, as Breaking Through reveals. Her family was close-knit and the state at least encouraged education. And Karikó was a worker. “I don’t consider myself especially smart, but what I lacked in natural ability, I could make up for in effort,” she says.

A vial of Pfizer’s Covid vaccine

A vial of Pfizer’s Covid vaccine. Photograph: Rogelio V Solis/AP

She took summer science classes, became a biology student at Szeged University and eventually obtained a PhD there. Aged 22, she fell in love with Béla Francia, a trainee mechanic five years her junior. They married, and in 1982 Karikó gave birth to their daughter, Susan. Two years later they moved to the US with their entire savings – about £900 – that were sewn inside Susan’s teddy bear to avoid Hungary’s currency restrictions.

By this time, Karikó had become obsessed with messenger RNA (mRNA), the material responsible for translating our DNA into proteins, the molecules from which we are constructed. Crucially, mRNA is extremely difficult to work with because it is fragile and short-lived. But Karikó was convinced it could play a major role in medicine and constantly fought for it to be a research focus. Few colleagues agreed, dubbing her “the crazy mRNA lady”.

Such epithets were a minor headache, however. At Temple University, in Philadelphia, where she began her work in the US, her chief, Robert Suhadolnik – after initially being supportive – tried to have her deported because she had had the temerity to seek a post at another university.

Eventually she moved to the University of Pennsylvania. Again, things went well at first, but as she maintained her mRNA obsession, the university began criticising her failure to attract grants. She was demoted, refused tenure, had her pay cut and finally found her possessions dumped in a hallway.

Given one of the first Covid shots to be administered in the US, she recalls, ‘My eyes grew misty’

Fortunately for Karikó – and the rest of the world – her obsession with mRNA was now shared by several other scientists and she was snapped up by the German company BioNTech to begin work on mRNA medicines.

The rest is scientific history. When Covid-19 struck, BioNTech and Karikó realised they were in a prime position to tackle the pandemic, and with the backing of the pharmaceutical giant Pfizer, developed a vaccine that played a key role in helping to protect the planet against the worst vicissitudes of coronavirus.

How this success affected Karikó is explained in one of the most moving moments in Breaking Through. She returned to Penn to be given one of the first Covid shots to be administered in the US. Karikó was spotted in the crowd and she was hailed, as a vaccine inventor, with roars of approval. “My eyes grew misty,” she recalls.

This is a vividly written, absorbing memoir of a life filled with triumphs (including her daughter Susan’s own successes as an Olympic gold medal-winning rower) over near-constant adversity. The precise reasons for the continual undermining of her research and academic prestige are left open, though Breaking Through hints that science today suffers because it requires its practitioners to publish papers in numbers rather than merit and to seek grants for safe research, as opposed to risky but potentially groundbreaking work. Quantity not quality has become a career driver.

Ironically, the last laugh for Karikó is missing from Breaking Through. Along with Drew Weissman, she won the Nobel prize for physiology in October 2023 – too late for inclusion in her book. What those who thwarted her research must think about this final success can only be guessed. One thing is clear, however. Her old laboratory may not yet be a museum, but it surely will be one day.

Breaking Through: My Life in Science by Katalin Karikó is published by Bodley Head (£22). To support the Guardian and Observer order your copy at guardianbookshop.com. Delivery charges may apply

COMMENTS:
Everyone is saying that this book should be widely read — by administrators as well as scientists. I might add that we need to include study section members and federal administration officials who decide who does vs who does not receive funding for their proposed project.

Instead of being approved to repeat and confirm some established finding, principal investigators need to be approved for “cutting-edge, risky proposals” (“outside the box” proposals) designed to move the field forward to the next level. More than several times, I’ve seen a grant turned down because “the proposed research is novel and therefore too risky” to be funded. ☹
DwN

Daniel
Probably just as important, there should be mandatory reading for Division/Department Directors and Research Administrators.

Ray
I have read the book, and it should be mandatory reading — starting with all academic supervisors and administrators. Not to mention the editor of Science, editor of Nature, etc.

Doron
Touching story! Thank you for sharing this with us. I knew some of the details, but this is a really nice detailed report. Who knows how many potential Nobels give up and never get the prize… but she didn’t!

Posted in Center for Environmental Genetics | Comments Off on Breaking Through: My Life in Science by Katalin Karikó review – real-life lessons in chemistry

A HORRIFIC STORY OF DISHONESTY IN PUBLISHING SCIENTIFIC PAPERS

It was about 2004 that publishing companies began publishing scientific manuscripts online, rather than in paper journals. GEITP is guessing that PLoS Publishing Company was first (and it remains honest and legitimate). But it didn’t take long before somewhat shady, to downright fraudulent, “predatory online open-access journals” began to pop up. By 2014, there were at least 4,500 “predatory journals” and today there are probably more than 18,000.(!!)

Over the past 15 years, GEITP has discussed many of these fraudulent publisher stories (https://genewhisperer.com/). One extreme example was a “family of four, living in a tiny house in a small village in Turkey, using their kitchen table as their ‘publishing company’, and raking in $1.2 million in one year (without paying any taxes).” The modus operandi is always similar: [a] recruit for “papers” (even if they’re only one or two pages in length), [b] pretend they are quickly “peer-reviewed” (which may or may not be the case), [c] accept the manuscript quickly, almost always without any need for modifications, and [d] charge an exorbitant amount of money in “page charges” to have “your manuscript published quickly online.”

One major factor in considering an academic PhD or MD for a position, or promotion to a higher position — is the “number of publications” the applicant reports. [In some circles, the “number of publications only in highly prominent journals” is an important criterion, but that’s not the case for the vast majority of hiring and promoting of individuals in academia, worldwide.]

And then, in 2009, we should all remember the Sokal Hoax [ https://physics.nyu.edu/faculty/sokal/ ] in which a physicist wrote a completely gibberish paper and submitted it to what was considered one of the better journals in the field (Social Text). And the paper supposedly got peer-reviewed and published anyway. The editors later backtracked by saying that they thought the paper “lacked originality, that it wasn’t well written, that they just accepted it as a favor to Dr. Sokal, a physicist, visiting their rigorous area of study, and so on” — but the fact remains that an editor should be able to distinguish a valid paper from a pile of garbled nonsense.

During the last 6-8 years, it has become popular to “tack on the names of coauthors from the same institute or hospital who were not actually involved with the research,” to help these individuals in getting hired and/or promoted (i.e., maybe five scientists did all the work and writing the manuscript — but another 18 physicians, in need of “more publications”, had their names inserted in the middle of the co-authorship list). GEITP has also covered such fraudulent stories in the recent past.

Now comes the latest [see attached Jan 2024 editorial]: shady “companies,” churning out fake papers, have decided to bribe journal editors.(!!) Exploiting the growing pressure on scientists worldwide to amass publications — even if they lack resources to undertake quality research — these sneaky intermediary “companies” (by some accounts) pump out tens, or even hundreds, of thousands of articles every year. Many contain fictional data; others are plagiarized, or of low quality. Regardless, authors pay to have their names on them, and these “paper mills” can make tidy profits.

Nicholas Wise (a fluid dynamics researcher at the University of Cambridge (England), moonlights as a scientific fraud buster; he was digging around on shady Facebook groups and saw something new. Rather than targeting potential authors and reviewers, someone (who calls himself “Jack Ben”, from a firm whose Chinese name translates as “Olive Academic”) was approaching journal editors — and offering them large sums of cash, in return for accepting papers for publication. [Even a spokesperson for Elsevier said every week its editors are offered cash in return for accepting manuscripts.]

“Sure, you will make money from us,” “Ben” promises prospective collaborators in a document linked to the Facebook posts, along with screenshots showing transfers of as much as $20,000 or more. More than 50 journal editors have already signed on, he wrote. There was even an online form for interested editors to fill out.

According to a new preprint, more than half of medical residents in one country admit they have engaged in research misconduct — such as buying papers or fabricating results. One reason is that publications, although no longer always a strict requirement for career advancement, are still the easiest path to promotion in a range of professions — including doctors, nurses, and teachers at vocational schools, according to sources. Yet these groups may have neither the time nor the training to do serious research. In such a setting, paying a few hundred or even a thousand dollars to see one’s name in print may seem a worthwhile investment.

Everyone is invited to read the complete amazing story in the attached pdf file.(!!)

For scientists about to submit their manuscript and who are wondering how to select an honest journal versus a “predatory online open-access journal” — you are encouraged to contact the “Membership in the Directory of Open Access Journals” or the “Open Access Scholarly Publishers Association.” These are good indicators that are able to confirm whether a journal is not predatory. You can check these sites to help you determine that the journal in which you are interested is legitimate. Also, please read this interesting 2020 publication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237319/ and these 2024 updated library guidelines as to “how to determine whether your selected journal is legitimate or predatory”: https://nuim.libguides.com/openaccess/predatory

DwN

Science 19 Jan 2024; 383: 252-255

Posted in Center for Environmental Genetics | Comments Off on A HORRIFIC STORY OF DISHONESTY IN PUBLISHING SCIENTIFIC PAPERS

The Scientific Method and Critical Thinking

What I see is government-funded scientists forgetting the progress in scientific thought in the 19th century, especially Germany. Hermann Helmholtz, about the most noteworthy denounced the way Goethe and Hegel and Aristotle processed scientific thought. Aristotle, unquestionably one of the greatest minds that ever lived, believed that all truth can come from reasoning alone. Francis Bacon, Voltaire, Descartes, and Galileo introduced the need for observation and experiment in science. The whole point of science is to understand nature, and if nature doesn’t abide by your theories, nature can’t be wrong. You are wrong and need to revisit your research.

Nobel Laureate physicist Richard Feynmann, who pinpointed the cause of the Challenger space shuttle disaster, emphasized the importance of experiment:

If you’re doing an experiment, you should report everything that you think might make it invalid—not only what you think is right about it…Details that could throw doubt on your interpretation must be given, if you know them.

So, a scientist, to be worth anything, must want to understand nature.

Posted in Center for Environmental Genetics | Comments Off on The Scientific Method and Critical Thinking