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

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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.

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SCIENTIFIC AUTOBIOGRAPHY

I received an invitation in July 2022 — to write “my scientific autobiography,” to be published in the 2024 issue of Annual Review of Pharmacology and Toxicology (APRT). The rules involved a “20-page maximum, which should include proposed figures and tables.”

My original draft was submitted at the end of Jan 2023; exactly 20-page limit. Each draft was peer-reviewed (by I don’t know how many people) multiple times, and I kept receiving comments: “Let’s talk less about this, and expand more about that.” “Please add a ‘family origins’ section at the start.” “You must add a ‘Legacy’ section.” “Did you plan your career?” “What future directions do you suggest for each of your projects?” “What fundamental pharmacological and toxicological rules did you learn over your 50-year career?”

For each question, my initial response was “Then, I’ll have to delete something in order to add that section to my article.” Their reply was “Go ahead and just add the section; we <> give you some wiggle room (beyond that initially-proposed 20-page limit).” 2023 was a roller-coaster year of additions, modifications, and subtractions, but the preprint was completed in Oct, and then this Jan 2024 final is considerably modified further and updated from that preprint (total pages of my article spills over onto page 26). The attached also includes Table of Contents of the 600+ page 2024 volume, plus a list of “Related Articles.”

Only one or two invited scientific autobiographies are planned for each year in the ARPT, so this has been quite a special honor. 😊😊

DwN

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Power of inclusion: Enhancing polygenic prediction with admixed individuals (simplified)

I apologize. Yesterday’s GEITP blog was regarded by some “as a bit difficult to understand” (i.e., “more basic background” is needed, please). So, here goes:

For more than two decades, genome-wide association studies (GWASs) have unequivocally shown that common complex disorders have a polygenic genetic architecture — which has allowed researchers to identify genetic variants (changes in DNA sequence) that are associated with specific diseases. For some traits, dozens or hundreds of single-nucleotide variants (SNVs) have been found to be associated. The “winner” to date is the trait (phenotype) for HEIGHT in which 12,111 SNVs are involved…!!

Many traits can be dissected by GWAS studies, and the hope is that the discovery of unexpected genes might help explain etiology or improve treatment. An intriguing (gene-environment) example I received today is a genetic test to forewarn the physician (and Parkinsonian patient) that dopamine agonists (in a subgroup of patients) can cause an unwanted adverse reaction, ICD (i.e., who wants to treat a horrible disease like PD, by giving a drug that makes things worse??):

Impulse control disorders (ICDs) often appear in people with Parkinson disease (PD), specifically those treated with a class of drugs called dopamine agonists. Newly published research, funded in part by The Michael J. Fox Foundation (MJFF), suggests genetic data can help provide warnings to those at the highest risk. If doctors are able to assess ICD risk consistently, it would help them warn people about ICDs and personalize treatments to minimize that risk.

Currently, doctors often use dopamine agonists to treat Parkinson’s disease. These agonists stimulate activity when binding with dopamine receptors, which can help alleviate Parkinson’s symptoms like motor challenges. However, the rise in use of dopamine agonists has caused ICDs to appear more commonly.

Knowing a person’s risk for developing an impulse control disorder can help chart their treatment path. For example, a doctor might choose a dopamine replacement like levodopa if their patient is at high risk for an ICD, while they might choose a dopamine agonist (which mimics, rather than replacing) for someone with a lower risk.

The authors of a paper recently published in the Annals of Clinical and Translational Neurology, led by a team at the University of Pennsylvania, say they can now use genetic data (along with other risk factors) to determine a person with Parkinson’s risk of developing ICDs. Knowing that risk allows for more individualized approaches (“precision medicine”) to their treatment — such as substituting dopamine agonists with dopamine replacements.

Taking all variants (DNA nucleotide changes) in each individual patient’s whole genome — can further be combined into a polygenic risk score that captures part of an individual’s susceptibility to come down with a specific disease. PRSs have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual’s lifetime genetic risk of disease, but the current discriminative ability is low in the general population.

Clinical implementation of PRSs may be useful in cohorts (the larger the N of genomes, the better) where there is a higher prior probability of disease (e.g., in early stages of diseases to assist in diagnosis or to inform treatment choices). Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual’s PRS from a percentile of a normal distribution to a lifetime disease risk. In the attached review, it was confusing that the authors used “polygenic scores” (PGSs) instead of “polygenic risk scores” (PRSs), But the authors emphasized that larger numbers of non-European samples, and authors demonstrated by simulation that larger numbers of “admixed” individuals (two or more ethnicities in the same person, which is becoming increasingly common these days) — will increase the power of statistical correlations (the larger the N of admixed genomes, the better).

DwN

From: Nebert, Daniel (nebertdw)
Sent: Wednesday, January 17, 2024 4:29 PM

Polygenic scores (PGSs) are used for combining genetic effects into the individual-level genetic liability of diseases or non-disease traits (e.g., risk of type-2 diabetes or schizophrenia; risk of lung cancer as a function of cigarettes smoked, or skin cancer as a function of arsenic exposure in drinking water). PGSs have attracted substantial research interest — as a result of the recent expansion of genotyped cohort sample sizes, increased appreciation of the polygenicity of complex traits, and recent methodological innovations and advances in PGS training. For some traits, the predictive performance has improved the potential clinical relevance of PGS.

However, most PGS models suffer from limited transferability across populations — despite the fact that some complex traits manifest substantial trans-ancestry genetic correlation (i.e., correlations of genes across ethnic groups). The limited transferability is partly due to the underrepresentation of non-European individuals in genetic studies and results in delaying the realization of equitable healthcare benefits from advancements in genetic research.

Several efforts are underway to improve the transferability of PGS models. First, active recruitment of non-European individuals in genetic studies, along with global partnerships and capacity building, are significantly increasing. However, most genome-wide association study (GWAS) cohorts have not yet comprehended the vast diversity that proportionally represents global populations. Second, the development of computational methods can complement these efforts and provide immediate benefits to individuals of diverse ancestry groups. Existing efforts include performing PGS modeling — by prioritizing variants present in diverse populations, and cell-type-specific regulatory elements — and combining multiple polygenic predictors characterized for multiple ancestry groups.

Admixed individuals (whose genomes consist of haplotypes from more than one ancestry group and account for one in seven newborns in the U.S.) are often excluded in PGS model training, given the technical limitations. Most modern PGS methods apply Bayesian multivariate regression by including GWAS summary statistics and ancestry-matched linkage disequilibrium (LD) reference panels. Although methods of applying GWAS analysis to admixed individuals exist, dependencies on the LD reference panels and computational complexities in representing LD for admixed individuals present challenges in the estimation of variant-effect sizes in PGS modeling.

However, including admixed individuals offers valuable insights into the genomic basis of common complex traits. A recent study indicates that the individual-level PGS performance shows linear decay as a function of genomic distance — defined as the Euclidean distance on the genotype principle-component analyses (PCA) projection from the PGS training set; this highlights the importance of considering the continuum of genomic ancestry in PGS evaluation. Given the substantial trans-ancestry genetic correlation in some complex traits, one might expect that admixed individuals can also offer unique opportunities to train PGS models with improved transferability.

Authors [see attached pdf] presented inclusive PGS (iPGS) — which captures ancestry-shared genetic effects by finding the exact solution for penalized regression on individual-level data. This approach is naturally applicable to admixed individuals. Authors validated their approach in a simulation study across 33 configurations with varying heritability, polygenicity, and ancestry composition in the training set. When iPGS is applied to N = 237,055 ancestry-diverse individuals in the UK Biobank, it shows the greatest improvements in Africans (by 48.9%) on average across 60 quantitative traits and up to 50-fold improvements for some traits (e.g., “neutrophil count”, R2 = 0.058) over the baseline model trained on the same number of European individuals.

When authors allowed iPGS to use N = 284,661 individuals, they observed an average improvement of 60.8% for African, 11.6% for South Asian, 7.3% for non-British White, 4.8% for White British, and 17.8% for “other individuals”. Authors further developed iPGS + refit — to jointly model the ancestry-shared and ancestry-dependent genetic effects when heterogeneous genetic associations were present. For “neutrophil count”, for example, iPGS + refit showed the highest predictive performance in the African group (R2 = 0.115), which exceeds the best predictive performance for the White British group(!!) (R2 = 0.090 in the iPGS model) — even though only 1.49% of individuals used in the iPGS training are of African ancestry. Authors declared that their data shows the power of including diverse individuals for developing more equitable PGS models. 😊

DwN

Am J Hum Genet 2 Nov 2023; 110, 1888–1902

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Power of inclusion: Enhancing polygenic prediction with admixed individuals

Polygenic scores (PGSs) are used for combining genetic effects into the individual-level genetic liability of diseases or non-disease traits (e.g., risk of type-2 diabetes or schizophrenia; risk of lung cancer as a function of cigarettes smoked, or skin cancer as a function of arsenic exposure in drinking water). PGSs have attracted substantial research interest — as a result of the recent expansion of genotyped cohort sample sizes, increased appreciation of the polygenicity of complex traits, and recent methodological innovations and advances in PGS training. For some traits, the predictive performance has improved the potential clinical relevance of PGS.

However, most PGS models suffer from limited transferability across populations — despite the fact that some complex traits manifest substantial trans-ancestry genetic correlation (i.e., correlations of genes across ethnic groups). The limited transferability is partly due to the underrepresentation of non-European individuals in genetic studies and results in delaying the realization of equitable healthcare benefits from advancements in genetic research.

Several efforts are underway to improve the transferability of PGS models. First, active recruitment of non-European individuals in genetic studies, along with global partnerships and capacity building, are significantly increasing. However, most genome-wide association study (GWAS) cohorts have not yet comprehended the vast diversity that proportionally represents global populations. Second, the development of computational methods can complement these efforts and provide immediate benefits to individuals of diverse ancestry groups. Existing efforts include performing PGS modeling — by prioritizing variants present in diverse populations, and cell-type-specific regulatory elements — and combining multiple polygenic predictors characterized for multiple ancestry groups.

Admixed individuals (whose genomes consist of haplotypes from more than one ancestry group and account for one in seven newborns in the U.S.) are often excluded in PGS model training, given the technical limitations. Most modern PGS methods apply Bayesian multivariate regression by including GWAS summary statistics and ancestry-matched linkage disequilibrium (LD) reference panels. Although methods of applying GWAS analysis to admixed individuals exist, dependencies on the LD reference panels and computational complexities in representing LD for admixed individuals present challenges in the estimation of variant-effect sizes in PGS modeling.

However, including admixed individuals offers valuable insights into the genomic basis of common complex traits. A recent study indicates that the individual-level PGS performance shows linear decay as a function of genomic distance — defined as the Euclidean distance on the genotype principle-component analyses (PCA) projection from the PGS training set; this highlights the importance of considering the continuum of genomic ancestry in PGS evaluation. Given the substantial trans-ancestry genetic correlation in some complex traits, one might expect that admixed individuals can also offer unique opportunities to train PGS models with improved transferability.

Authors [see attached pdf] presented inclusive PGS (iPGS) — which captures ancestry-shared genetic effects by finding the exact solution for penalized regression on individual-level data. This approach is naturally applicable to admixed individuals. Authors validated their approach in a simulation study across 33 configurations with varying heritability, polygenicity, and ancestry composition in the training set. When iPGS is applied to N = 237,055 ancestry-diverse individuals in the UK Biobank, it shows the greatest improvements in Africans (by 48.9%) on average across 60 quantitative traits and up to 50-fold improvements for some traits (e.g., “neutrophil count”, R2 = 0.058) over the baseline model trained on the same number of European individuals.

When authors allowed iPGS to use N = 284,661 individuals, they observed an average improvement of 60.8% for African, 11.6% for South Asian, 7.3% for non-British White, 4.8% for White British, and 17.8% for “other individuals”. Authors further developed iPGS + refit — to jointly model the ancestry-shared and ancestry-dependent genetic effects when heterogeneous genetic associations were present. For “neutrophil count”, for example, iPGS + refit showed the highest predictive performance in the African group (R2 = 0.115), which exceeds the best predictive performance for the White British group(!!) (R2 = 0.090 in the iPGS model) — even though only 1.49% of individuals used in the iPGS training are of African ancestry. Authors declared that their data shows the power of including diverse individuals for developing more equitable PGS models. 😊

DwN

Am J Hum Genet 2 Nov 2023; 110, 1888–1902

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**HGNC Newsletter** Autumn 2023

The Human Genome Organization (HUGO) was conceived in 1988 at the first meeting on genome mapping and sequencing at Cold Spring Harbor. Its original purpose was to promote international collaborative efforts to study the human genome and to address the myriad issues raised by knowledge of the genome — including ethical and societal questions and issues involving nomenclature. Beginning with 42 scientists from 17 countries, HUGO has increased its membership base today to more than 1,200 members from 69 countries.
In 2008, HUGO passed its 20th anniversary and decided on a change in its direction. With the original goal of sequencing the human genome accomplished, HUGO decided to focus on two outstanding issues: First, HUGO will explore the medical implications of genomic knowledge ( i.e., to seek the biological and medical meaning of genomic information — genomic medicine); and second, to enhance the genomic capabilities and to help fulfill the genomic aspirations of the emerging scientific countries of the world. The excitement and interest in genomic sciences in Asia, Latin America, the Middle East, and Africa are palpable; and the hope is that these technologies will help in national development and health, worldwide.
So, it is in these two areas in which HUGO will focus on over the ensuing years: the expansion of genomic medicine and greater engagement with the emerging scientific countries. This also includes the HUGO Gene Nomenclature Committee (HGNC), which details their progress in reports four times a year. Instead of stripping-and-pasting into an email (as I’ve always done), it is now more convenient to simply provide the URL, and interested GEITP’ers can click on it and learn the latest in gene nomenclature, if they so wish. Please click on the URL [below] to see the Autumn 2023 issue.
DwN

https://nam11.safelinks.protection.outlook.com/?url=https%3A%2F%2Fblog.genenames.org%2Fhgnc%2F2023%2F11%2F23%2FAutumn_newsletter_2023&data=05%7C01%7CNEBERTDW%40UCMAIL.UC.EDU%7C7a1ffa186fde45a6a22908dbf0282a90%7Cf5222e6c5fc648eb8f0373db18203b63%7C0%7C0%7C638367827532663382%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=36eKkPny3c2IjQ4bUHNXXfe5g3YaU%2BZCwEK%2FY8R373o%3D&reserved=0

If you have questions or comments on our newsletter or on any human gene nomenclature issue, please email us at: hgnc@genenames.org

————————————————————————-
HUGO Gene Nomenclature Committee (HGNC)
European Bioinformatics Institute (EMBL-EBI) European Molecular Biology Laboratory Wellcome Genome Campus Hinxton, Cambridgeshire
CB10 1SD, UK

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CO2 Rocks! From Hot Rocks to Cool Rocks

CO2 Rocks! From Hot Rocks to Cool Rocks

By Bob Hoye

When reviewing the history of our atmosphere, it is fascinating that at first it was all atmosphere and no Earth. And it was mainly hydrogen. Then, due to the implacable nature of gravity, enough of it got together to form our hot Sun, while other clumps of matter accreted into the gaseous, as well as the rocky, planets of which the Earth eventually became the most accommodating for life to appear and prosper.

Over immense time, the open hospitality changed the atmosphere and the rocks. Initially, hot rocks mainly emitted nitrogen and some carbon dioxide. Moreover, hot rocks have continued outgassing CO2 ever since. And then life was initiated by very early forms of bacteria arriving, which — with RuBisCO, followed later by photosynthesis — provided not just oxygen, but converted CO2 to food. All on the way to forming cool rocks.

And beyond this, without carbon dioxide, life as we know it would not exist.

Most folk don’t mind cool rocks and really enjoy warm coral beach sands. But in the face of strident threats that rising temps and ocean levels are going to kill coral reefs, people should look up the history of coral.

Some forms of coral have been around for hundreds of millions of years surviving huge changes in temperatures and changes in sea levels. And right now, the temperature for the Great Barrier Reef’s north end is 5 degrees Celsius higher than at the south end. Corals are happy at either end — and in between.

And just since the coldest with the last ice age, such reefs have endured a 10-degree (Celsius) increase in global temps and a hundred-meter increase in sea levels.

They know how to survive.

Obviously, tropical corals just don’t care where the sea level is so long as they are there. For cold water corals that thrive on ocean floors, they don’t care where the sea level is either.

Nowadays, some 99% of our atmosphere is nitrogen and oxygen. More detailed at 78% and 21%, with the next most present being argon at 0.93%. Carbon dioxide at only 0.04% is ranked as one of the trace gasses.

Of course, the main “greenhouse gas” is water vapor which can range as high as 7% in the humid tropics to 1% in a frigid climate. And what we breathe out includes CO2 at some 5% with some 6% being water vapor. (https://www.CO2coalition.org).

.

And water as a liquid or as gas is a huge transporter of heat from hot to cool places In the real world, carbon dioxide contributes little to transporting heat, nor as a gas does it store any heat. (https://climatechangedispatch.com/physicist-co2-heat-retention/).

And recorded changes in climate trends have been driven mainly by changes in the Sun’s activity and changes in the Earth’s orbit; CO2 has negligible influence. (https://science.sciencemag.org/content/235/4792/973).

However, a crazed media, their bureaucrats, and politicians have turned it into a molecule with a very scary political mojo – making fear an industry for ambitious governments. Instead of suffering undeserved infamy, carbon dioxide molecules should be celebrated.

Indeed, in its essential role of providing food for life, the observation is that CO2 rocks! The quip is practical because carbon dioxide came from — and still comes from — hot rocks and, in sustaining life, is eventually turned into cool rocks. Otherwise known as corals or, with chemical variation, rocks originating from carbon dioxide have been called limestone or dolomite. While enjoyed as mountain scenery at, say, Aspen or Davos, it really is magnificently sequestered carbon dioxide. With alteration due to heat and pressure, either rock can be appreciated as fine marble.

Life, of which humans are a very small portion, is an essential intermediary step in transporting CO2 from one kind of rock to another kind of rock. Hopefully forever.

Originally, life was made possible by a special critter known as cyanobacteria; and if society needs to know only one equation, it should be the one for photosynthesis:

Carbon dioxide + Water + Sunshine = Glucose + Oxygen

The Dictionary of Science by Hammond and Barnhart provides concise detail.

“Photosynthesis occupies a primary place in the economy of life. It is the process by which the energy of the Sun is captured and converted to the uses of the living cell. It is, in addition, the beginning process in the transfer of atoms from the inorganic to the organic.”

Not only does CO2 make rock, but it adds up to mountains of the stuff. Indeed, the Dolomite Mountains rise as high as 11,000 feet, which is the ultimate in bleached-out and ocean-deprived coral reefs. The foundations of such mountains go down thousands of feet below today’s sea levels. Representing an enormous sequestration of carbon dioxide that is visible, unseen are the vast cold-water corals on many ocean floors.

Hot rocks, under the sea and in fiery archipelagoes or rifts, as well as ocean waters are always outgassing CO2. The key step is to place industrial society’s emissions in perspective. Using the Vostok core of temps and CO2 concentrations, the record shows that climate warming precedes CO2 increases by some 800 years. Increasing temps force increases in CO2, not the other way around.

So, some rocks provide life-giving carbon dioxide, which lately as a means of raising taxation and imposing regulations has been getting a bad rap. Unwarranted!

And, going the other way, rocks have been remarkable in sequestering CO2. Indeed, during the Cambrian Period some 550 million years ago, atmospheric concentrations were at 7,000 ppm, or 0.70%, some 17 times higher that today’s paltry 400 ppm. (https://i.stack.imgur.com/HxERL.png).

And where did all of that atmospheric CO2 go? Quite simply, it became rocks on the ocean floors or stacked up in scenic mountains.

Geologically speaking, today’s atmospheric concentrations are rather low. Moreover, at lower than 150 ppm, all life on our formerly hospitable planet would begin to shut down.

Sea-level corals and other critters have been quietly turning a politically powerful trace gas into traceable rock. That it works within natural geological trends is recorded by the long rise in sea levels of around 100 meters since the start of the latest interglacial, some 12,000 years ago. Along with this has been the 10-degree Celsius rise in temperature.

In looking to the optimistic side, corals are still turning CO2 into cool rocks. They thrive in tropical temperatures and don’t care if the sea level is going up or down. Wherever it is, they will be there. They have been doing it for hundreds of millions of years.

Understandably, the recent rise in carbon dioxide levels has been accompanied by the remarkable “greening” of global vegetation. As measured by satellites, wherever plants grow — from the poles to the tropics or from the seas to rocky mountain highs. Thanks to CO2 in its diverse forms, life exists — and for mankind, it’s the best that it has ever been.

As a postscript, for those who have the audacity to imagine that committees can “manage” the temperature of the nearest planet — don’t waste time and money on CO2. Go to where efforts will be effective: you might want to change the solar cycle, cosmic rays, the Earth’s orbit, plate tectonics, and/or ocean currents.

CO2 Coalition Member Bob Hoye received his B.Sc. in Geology, geophysics from the University of British Columbia. Hoye has many published articles in the leading media and has addressed investment forums in many countries.

COMMENT:
Hi Magnus,

I could not agree more. If the Am J Hum Genet manuscript had received a more robust peer review — it likely would have been rejected from publication in that high-visibility journal. ☹

Wow. There are now 807,162 genome sequences (available for data mining) worldwide — from eight geographically distinct ethnic subsets in gnomAD v.4 (!!!!) 😉

DwN

From: Magnus Ingelman-Sundberg
Sent: Monday, November 6, 2023 1:00 AM

Hi Dan,

There is nothing special or novel in this paper. Previous papers have included [e.g., Pharmacogenomics J. Dec 2022; 22: 284-293. The genetic landscape of major drug-metabolizing cytochrome P450 genes — an updated analysis of population-scale sequencing data. Yitian Zhou & Volker M Lauschke. PMID: 36068297 (https://pubmed.ncbi.nlm.nih.gov/36068297/) ] with essentially the same message. Here [in the attached AJHG pdf] they only show that the genetic variation is also evident in the UK biobank.

The gnomAD has recently been updated to version 4 [pasted below], which includes genetic variation data from individuals almost 5x larger than the combined v2/v3 versions. The UKBiobank data is also included in the v4 version. This new version 4 is ideally a much better resource for pharmacogenomic allele frequencies.

A screenshot of a data table Description automatically generated

Best M.

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Meta-analysis of GWAS of gestational duration, and spontaneous preterm birth, identifies new maternal risk loci

GEITP is aware that this project has been a focus of Ge Zhang [Division of Genetics, Cincinnati Children’s Hospital] for >6 years; finally, the results are published and can be shared [see attached]. 😊 More than 15 million pregnancies per year, worldwide, are affected by preterm births (i.e., <37 weeks of gestation); there are no effective ways to prevent preterm births, and premature babies suffer from more neonatal mortality and lifelong morbidities, compared with full-term babies. Genetic factors of mother and fetus explain a large proportion (~30–40%) of the variation in gestational age at delivery (thus, this topic is consistent with the “gene-environment interactions” theme of these GEITP emails). To date, there have been only a few unbiased genome-wide investigations — designed to locate these genes. Recent genome-wide association studies (GWASs) have identified some robust associations. For example, variants in genes including WNT4 (Wnt family member-4), EBF1 (EBF transcription factor-1), AGTR2 (angiotensin II receptor type-2) and KCNAB1 (potassium voltage-gated channel subfamily A regulatory beta subunit-1) have been associated with timing of birth in mothers, and a study with fetal samples discovered a locus near genes that encode pro-inflammatory cytokines associated with gestational duration. Authors hope that better characterization of causal genetic mechanisms could lead to new strategies to treat and prevent preterm births. Authors conducted a genome-wide meta-analysis of gestational duration, and spontaneous preterm birth, in 68,732 and 98,370 European mothers, respectively. The meta-analysis detected 15 loci associated with gestational duration, and four loci associated with preterm birth. Seven of the associated loci were novel: WNT3A (Wnt family member-3A), RHAG (Rh-associated glycoprotein), KCNN2 (potassium calcium-activated channel subfamily N member-2), COBL (cordon-bleu WH2 repeat protein), GNAQ (G protein subunit alpha q), GC (vitamin D-binding protein), and LINC02824 (long intergenic non-protein coding RNA 2824). The loci mapped to several biologically plausible genes, for example, HAND2 (whose expression was previously shown to decrease during gestation) was associated with gestational duration, and GC was associated with preterm birth. Downstream in silico-analysis suggested regulatory roles as underlying mechanisms for the associated loci. Linkage disequilibrium (LD) score regression found birth-weight measurements as the most strongly correlated traits — highlighting the unique nature of the spontaneous preterm birth phenotype. Tissue expression and co-localization analysis revealed reproductive tissues and immune cell types as the most relevant sites of action. The authors’ findings complement the knowledge (to date) of the genetic factors of preterm birth. 😊 DwN PLoS Genet Oct 2023; 19: e1010982

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The crusade against carbon dioxide and integrity in climate science

In September 2023, Princeton University’s Cyrus Fogg Brackett Professor Emeritus of Physics, William Happer, spoke at the Institute of Public Affairs (IPA) to an audience in Brisbane, Australia about the crusade against carbon dioxide and integrity in climate science. Will Happer is a member of the National Academy of Sciences (NAS), Physics Division, and has made fantastic contributions to the U.S. Defense and Space Programs.

Professor Happer is one of the world’s leading scientists and climate realists, having made extensive contributions to the debate about climate science. While in Australia, he gave similar talks in Perth, Sydney and Melbourne.

Preview of Professor William Happer IPA lecture – The Crusade Against Carbon Dioxide – September 2023

In my opinion, this is Professor Happer’s best-ever lecture on this topic and it is the best Climatology talk I have ever heard — in terms of giving a 47-min-long presentation on a complex subject in a down-to-earth, apolitical, folksy chat that is neither arrogant nor condescending nor intimidating — and which scientists in the field, as well as the lay public, will have no problem in understanding.

If you want to know the truthful scientific facts (as opposed to journalistic and politics hyperbole and hysteria), I encourage everyone to set aside an hour or two and learn the LATEST in the field. 😊 [I found that it’s easier to understand, if you click on “closed captions” (CC) — although the transcript includes a number of wrong words.] If you don’t want to know the truth, please delete without watching / listening.

His lecture (~47 minutes) can be downloaded here:

or here:

https://www.youtube.com/wath?v=v2nhssPW77I

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Pioneers of mRNA COVID vaccines win the 2023 Medicine Nobel

As I understand it — here is yet another example of a grad student or postdoc (perhaps in particular because she was a female?) being ridiculed, or passed over, while it was her original idea that represented the breakthrough. But Katalin Karikó persisted and is to be congratulated. 😊

DwN

Pioneers of mRNA COVID vaccines win medicine Nobel

Katalin Karikó and Drew Weissman laid the groundwork for immunizations that were rolled out during the COVID-19 pandemic at record-breaking speed.

Ewen Callaway & Miryam Naddaf

Drew Weissman, (left) MD, PhD, seated beside Katalin Karikó,(right) PhD.

Drew Weissman (left) and Katalin Karikó (right).Credit: PixelPro/Alamy

This year’s Nobel Prize in Physiology or Medicine has been awarded to biochemist Katalin Karikó and immunologist Drew Weissman for discoveries that enabled the development of mRNA vaccines against COVID-19.

The vaccines have been administered more than 13 billion times, saved millions of lives and prevented millions of cases of severe COVID-19, said the Nobel committee.

Karikó, who is at Szeged University in Hungary, and Weissman, at the University of Pennsylvania in Philadelphia (UPenn), paved the way for the vaccines’ development by finding a way to deliver genetic material called messenger RNA into cells without triggering an unwanted immune response.

They will each receive an equal share of the prize, which totals 11 million Swedish krona (US$1 million).

Karikó is the 13th female scientist to win a Nobel Prize in medicine or physiology. She was born in Hungary, and moved to the United States in the 1980s. “Hopefully, this prize will inspire women and immigrants and all of the young ones to persevere and be resilient. That’s what I hope,” she tells Nature.
A new chapter

The COVID-19 vaccines developed by Moderna and the Pfizer–BioNTech collaboration deliver mRNA that instructs cells to create copies of a protein that is found on SARS-CoV-2 virus particles, called the spike protein. This stimulates the body to make antibodies that target the protein, as well as triggering other immune responses.

For decades, mRNA vaccines were considered unfeasible because the injection of mRNA into the body triggered an immune reaction that immediately broke down the mRNA. In the mid-2000s, working at UPenn, Karikó and Weissman demonstrated that swapping one type of molecule in mRNA, called uridine, with a similar one called pseudouridine, bypasses the cells’ innate immune defenses1.

“I’m delighted to see them recognized,” says Robin Shattock, a vaccine scientist at Imperial College London, who has worked on mRNA vaccines. “Their contribution was really fundamental in the success of the COVID-19 vaccines, and I think will underlie RNA technology for some time to come.”

“They demonstrated that changing the type of the RNA nucleotides within the vaccine altered the way in which cells see it,” said John Tregoning, a vaccine immunologist at Imperial College London, in a press statement for the UK Science Media Centre. “This increased the amount of vaccine protein made following the injection of the RNA, effectively increasing the efficiency of the vaccination: more response for less RNA.”

“This discovery has opened a new chapter for medicine,” said Nobel committee member Qiang Pan Hammarström, an immunologist at the Karolinska Institute in Stockholm, at a press conference after the prize announcement. “Investment in long-term basic research is very important.”
Vaccine revolution

There are now mRNA vaccines in development for a number of other diseases, including influenza, HIV, malaria and Zika.

“It’s really like a revolution starting since the COVID pandemic,” says Rein Verbeke, an mRNA vaccine researcher at the Ghent University in Belgium. He adds that Karikó and Weissman’s contributions were essential to the vaccines’ success during the pandemic, and beyond. “Their part was really crucial to the development of this platform.”

A COVID-19 mRNA vaccine containing unmodified RNA, developed by CureVac, based in Tübingen, Germany, was widely seen as a flop after its mediocre performance in clinical trials.

Another key component of COVID-19 mRNA vaccines was the lipid nanoparticles (LNPs) that surround the modified RNA and ease its entry into cells. Numerous scientists contributed to the development of LNPs, says Verbeke, and it would have been nice if the Nobel committee had also recognized their contributions to mRNA vaccines. The modification of mRNA and the development of LNPs “were the two major steps that were necessary to have mRNA vaccines working”, he says.

Many people were involved in developing LNPs, however, and it would be difficult to single out any one contribution, says Pierre Meulien, who worked on using mRNA to trigger immune responses in the 1990s at Transgène, a small biotech firm near Strasbourg in France. Karikó and Weissman “really created the key to success of the whole enterprise around mRNA vaccines”, he adds.

The development of mRNA vaccines and therapeutics is still in its infancy, says Shattock. Scientists and biotechnology companies are busy coming up with new applications for mRNA technology, from cancer treatments to next-generation COVID-19 vaccines. Many teams are also working on improved ways of delivering mRNA. “What we see used today is not what’s going to be used in the future,” he says. “We’re at the beginning of an RNA revolution.”

Although COVID-19 jabs put mRNA vaccines on the map, the technology’s impact is likely to reach far and wide, says Karikó. “It is just limitless.”

doi: https://doi.org/10.1038/d41586-023-03046-x

Additional reporting by Katharine Sanderson.
References

Karikó, K., Buckstein, M., Ni, H. & Weissman, D. Immunity 23, 165–175 (2005).

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