Genes Genomics Genetics Epigenetics and the Environment

Having received numerous comments (both pro and con) to this 24 July 2026 GEITP blog [below], here is my balanced response:

[1] Who is this author (who is proposing that NAS members should approach this topic as scientists would do)?

Francis Menton received his B.A. in Economics and Mathematics summa cum laude from Yale University in 1972; and his J.D. degree cum laude from Harvard Law School in 1975. In 1975 he joined the law firm of Willkie Farr & Gallagher LLP as an associate, becoming a partner in 1984, and retiring after 40 years in 2016.

During his legal career, Mr. Menton specialized in the field of commercial litigation, with a national practice that entailed trying cases in dozens of courthouses around the country. He was best known for cases involving complex and technical subject matters, such as innovative financial and insurance products or the malpractice of actuaries.

In 2012 Mr. Menton launched the Manhattan Contrarian blog (www.manhattancontrarian.com), where over the ensuing 14 years he has published well over 1000 articles on issues of public policy. Close to one-third of the posts at Manhattan Contrarian deal with the subject of climate change broadly defined, including such topics as the application of the formal scientific method to what passes for climate “science” in today’s academia, and evaluation of the potential costs and practical difficulties of attempting to replace our current energy systems with intermittent wind and solar electricity generation.

[2] Menten suggests that NAS members should use the Scientific Method (as scientists are supposed to do)

WHAT IS THE SCIENTIFIC METHOD?

Define a question
Gather information and resources (observe)
Form an explanatory hypothesis
Test the hypothesis by performing an experiment and collecting data in a reproducible manner
Analyze the data
Interpret the data and draw conclusions that serve as a starting point for a new hypothesis
Publish results
Retest (frequently done by other scientists)

[3] Menten also suggests that NAS members should use Critical Thinking (as scientists are supposed to do)

WHAT IS CREATIVE THINKING?

Creative thinking is the ability to look at situations from new perspectives, generate original ideas, and find useful, innovative solutions to problems. It involves moving past standard, memorized answers to connect unrelated concepts and try flexible approaches.

Key Elements of Creative Thinking

Divergent thinking: Generating a large quantity of diverse ideas or alternative paths without immediate judgment
Open-mindedness: Welcoming unconventional concepts, diverse viewpoints, and unexpected possibilities
Curiosity: Constantly asking “why” and “what if” to explore deeper meanings and root causes
Experimentation: Testing ideas, taking risks, and treating failures as learning steps rather than final stops

[4] GEITP suggestions

The National Academy of Sciences (NAS) comprises 2,705 active U.S. members. A “report from the National Academy of Sciences” — cannot possibly mean that 2,705 “scientists” have the same opinion. Any collection of a group will obviously have some differences of opinion.

Michael Crichton, MD, stated — “There is no such thing as consensus science. If it’s consensus, it isn’t science. If it’s science, it isn’t consensus. Period” (6 March 2012).

A much more commonly accepted (scientific) approach would be to publish a “majority report” and a “minority report” and a “declaration of agreement or disagreement.” Members of the NAS (or any other organization) should have the CHOICE to declare “I am in favor of this “NAS report advocated by the leaders of my organization” — versus “I disagree … etc. because I have a background in climatology” versus “I am not sufficiently knowledgeable in (whatever field of science) to have a serious opinion on this topic.” ☹😊

DwN

From: Nebert, Daniel (nebertdw)
Sent: Friday, July 24, 2026 5:45 PM

This is a whimsical blog from The Manhattan Contrarian, written by a non-scientist…!! When I began in “science” in the 1960s, I had always heard of the highest honors of being accepted into the Natl Acad of Sciences. This fantasy seemed to dwindle in my mind, during the 1990s-2000s, however — when it became clear that the NAS, as well as many journals (Science, Nature, Sci Am) and woke scientific organizations (FASEB, SOT, ASPET, ASBMB, APS, ACS), became increasingly highly politicized and lost their individuality and scientific rigor… “Consensus” instead of “independent scientific rigor” is now what woke journalism wants…

DwN

Yet Another Embarrassment from the National Academy of (Pseudo)Sciences

July 23, 2026/ Francis Menton

In my own professional life, I was not a scientist, and therefore I never much paid attention to the kinds of rewards and honors that practicing scientists pass out to each other. But at some point, I became aware that there was something called the National Academy of Sciences, and that among scientists it was considered a big deal to get selected to become a member. This membership is one of those things that you cannot apply for; rather, one day you get “tapped” by some committee of super-elite gurus who invite you to come learn the secret handshake. Here’s what Wikipedia has to say about membership:

Membership of the National Academy of Sciences is an award granted to scientists that the National Academy of Sciences (NAS) of the United States judges to have made “distinguished and continuing achievements in original research”. Membership is a mark of excellence in science and one of the highest honors that a scientist can receive.

(At some point in the 2010s, the NAS got somehow consolidated with comparable “academies” of engineering and medicine, to become a combined organization going by the name of the National Academies of Science, Engineering and Medicine, or NASEM. This post only concerns the Science part of the combined entity, although I have no reason to think that the other parts are any better.)

There are only around 2000+ members of the NAS, out of a universe of some 2 million + people who do some kind of scientifically-related research. So only about one in a thousand gets in. Needless to say, these people must be really, really smart.

Well, as far as I can tell, they are all morons. Also, corrupt morons.

I last wrote about the NAS in February of this year, in a post titled “Would You Trust The National Academies Of Science To Tell You How Science Works?” The occasion for that post was that something called the Federal Judicial Center had just issued a new edition of its Federal Reference Manual on Scientific Evidence. Recognizing that this subject went outside the core of its own expertise, the FJC had called on the NAS to take the main role in the drafting. In the new edition, a chapter from prior editions of the Manual titled “How Science Works” had been taken over by new authors, and substantially re-written and greatly expanded (from 18 to 61 pages). In the process, the new authors had inserted a series of howlers that not only did not fairly describe how science works, but actually got the whole process wrong by 180 degrees. I cited several examples in the February post, but this is the one that goes closest to the heart of the craziness: “While the often-­stated maxim that correlation does not imply causation is true, in fact, correlation is the only means that we have of establishing causation in science.” That statement is just flatly wrong. Instead, the process for establishing causation in science operates through the falsification of alternative (“null”) hypotheses of causation. I do not know how anyone could even think to call themselves a “scientist” without basic understanding of that logical process.

And yet here was the NAS, supposedly a collection of the most elite among elite scientists, putting together a chapter of an official court Manual to tell non-scientists (lawyers and judges) “how science works,” and getting it 180 degrees wrong on the single most important point.

Which of course begs for a necessary consideration of the next question: Was this an innocent mistake by ignorant people, or was it an intentional distortion intended to further a political agenda?

Now, just last week, the National Academies have released their latest embarrassment, taking this fundamental fallacy and expanding and running with it. The event at issue was the release of a new Report called “Attribution of Extreme Weather Events and Their Impacts.” Here is the July 15 press release from NASEM, and here is another link to the body of the Report itself. The Report runs to some 175 pages, plus appendices.

The gist of the Report is that now, based on some sort of new research, we suddenly have the tools to “attribute” any extreme weather event of our choosing (hurricane, tornado, drought, flood, whatever) to “human activities.” “Human activities” in this context means the release of “greenhouse gases” into the atmosphere. With that, you can see where they are ultimately going, although this final piece is not mentioned in the Report: the basic idea is that every extreme weather event is the fault of the oil companies.

The very first line of the “Summary” reveals that they knew the conclusion before they started:

“Earth system changes driven by rising greenhouse gas concentrations from human activities are affecting characteristics of extreme weather and climate events, such as frequency and intensity.”

That’s nice. And how exactly do you know it? Here are the two fundamental questions that need to be addressed: (1) What are the alternative hypotheses that you have considered, and how have those been ruled out as the causes of the recent extreme weather events? And (2) what has been your consideration of the evidence, if any, that might contradict or undermine the hypothesis that “human activities” and increased greenhouse gas concentrations are the cause of these extreme weather events?

Get ready: In a Report of 175 pages, they don’t expend even one word to address either of those two questions.

Instead, it’s all about whatever confirming evidence they can find about correlation between extreme weather events and (slightly) increasing global temperatures. They claim to have a “foundational understanding” of the relationship between increasing greenhouse gases and extreme weather events. How they have achieved this “foundational understanding” without ever entertaining any alternative hypothesis is never mentioned. But the “foundational understanding” has supposedly been “strengthened” by the accumulation of evidence consistent with it (while deliberately ignoring all inconsistent evidence). Here is a lengthy quote from the Summary as to how the “foundational understanding” has been strengthened:

Over the past decade, advances in three key scientific pillars have continued to strengthen this foundation. First, physical understanding has matured through accumulation of observational and modeling evidence supporting long-standing theoretical expectations, so that increases in extreme heat and heavy rainfall events across much of the globe can be more confidently and precisely attributed to increasing greenhouse gas concentrations in the atmosphere. Second, the length and quality of observational data have improved in some regions with another decade of data collection . . . , new satellite-based Earth-observing missions, and the development and improvement of homogenized, high-resolution data sets. Third, climate models continue to improve in their representation of critical processes. . . .

Consideration of alternative hypotheses or potentially conflicting evidence? Hey, we don’t do that, we’re scientists!

Readers of this blog and of many skeptic websites know well that the real evidence out there is that extreme weather events are not increasing at all. How dozens of these supposedly top “scientists” from the NAS could write this Report without mentioning or discussing any of this evidence is beyond me. It’s completely humiliating for them.

I won’t try in this post to give any comprehensive set of links here to data sets showing that extreme weather events are not increasing. But, as an example, here is a page at Watts Up With That with data on hurricanes. From that page, here is a chart compiled by Ryan Maue with annual data since the early 1970s on accumulated cyclonic energy:

Can you spot the increasing trend? Neither can I. These clowns from the NAS are claiming that even though ACE has not gone up overall, and has gone down in the most recent years, they just know that whatever hurricane comes through next is the fault of Exxon. That’s the level of quality of this work.

On July 14, the day before this Report was released, a guy named Pat Parenteau, gave an interview to Politico’s E&E News on this subject. Parenteau is a long-time advisor to a law firm called Sher Edling, which is known for representing dozens of plaintiffs in lawsuits against fossil fuel producers claiming harm from climate change.

The E&E News article is behind paywall, but Energy in Depth here has the key quote from Parenteau:

“A report with the kind of gravitas that the National Academies can bring — will be a huge boost to the plaintiffs’’ cases.”
Further from EID:

The people involved in the report’s development include Michael Burger, an academic and attorney for climate plaintiffs’ firm Sher Edling, as well Delta Merner, who leads the Union of Concerned Scientists’ Climate Accountability Campaign and served on the NAS committee guiding the report’s development until January 2025. Both Burger and Merner have publicly discussed the critical relationship between attribution science and climate litigation

The federal government needs to completely defund the NAS today, if not sooner. Also, I call on every member of the NAS to resign. If you stay in, you are complicit in this total scam.

UPDATE, July 24: John Christy sends along links to two of his recent papers. The first, published in April 2026, is titled “Declines in hot and cold daily temperature extremes in the conterminous US, 1899–2025.” That’s right, it’s declines rather than increases. The second, from November 2019, co-authored with Ross McKitrick, is titled “Assessing changes in US regional precipitation on multiple time scales.” From the abstract of the second paper: “We show that 2000-year proxy-based reconstructions of the Palmer Modified Drought Index for the US Southeast (SE) and Pacific Coast (PC) regions exhibit LTP and reveal post-1900 changes to be within the range of longer-term natural fluctuations.” John says that an updated version of the second paper is currently under review pending publication. Needless to say, the NAS Report did not cite and completely ignored both of these two papers (along with all other adverse evidence).

Posted by Francis Menton.

Manhattan Contrarian – Economic, Political & Legal Commentary

This is an excellent relevant study in Risk Assessment — worthy of being shared with everyone on the GEITP email blog list. In biology, hormesis is a biphasic dose-response phenomenon in which a low dose of a stressor or toxicant has a beneficial or stimulatory effect on an organism, whereas high doses are toxic or inhibitory. Hormesis operates on the principle of “what doesn’t kill us will only make us stronger”. 😉😉

This paper [see attached pdf file] provides the first critical review of the capacity of per- and polyfluoroalkyl substances (PFAS) agents to induce hormetic effects in mammalian toxicological and biomedical cellular and animal models. PFAS-induced hormetic responses were reported in primary cells and cell lines from multiple organ systems (e.g., liver, lung, colon, breast, prostate, immune, brain) from animal models and humans. While more limited, PFAS also induced hormetic dose responses in experimental animals for short-term and chronic studies.

Hormetic effects were induced by long and shorter carbon-length-alternative PFAS agents, with hormesis dose-response features being similar. These PFAS-induced hormetic dose responses are consistent with quantitative features of hormetic responses of other chemical and physical agents, including PFAS effects on plants and ecological animal models. These findings suggest ways to optimize study designs to assess the nature of the dose response in the low-dose zone, including dose selection, number of doses, and dose spacing strategies. The findings present challenges for interpretations concerning what is an adverse effect — because some effects presented here may be desirable while others potentially harmful. The introduction of the hormesis concept into the hazard assessment process creates novel risk assessment considerations making the process more scientifically robust, creating a range of new regulatory options. These findings and those shown with plants and ecological animal models indicate that “the hormetic concept” should become a fundamental feature of ecological and human risk assessment principles and practices by regulatory agencies. 😊

DwN

Chem Biol Int, 25 June 2026; in press https://doi.org/10.1016/j.cbi.2026.112222

As a PhD student in the 1920s, embryologist Hilde Mangold conducted a strange experiment that transformed biology. She moved a lump of cells from embryos of one newt species into another. The transplanted cells caused a secondary ‘body axis’ to form in the host embryo, complete with a nervous system and a precursor to the spine. Mangold showed that much of the secondary body axis had been developed from the recipient embryo tissues.

The discovery of an embryonic ‘organizer’ that orchestrates the formation of a body axis “established a whole new area of developmental biology.” In a study published in Nature on 17 June [see attached pdf file], Kremnyov and his colleagues report the discovery of an embryonic organizer in marine predators called comb jellies (Ctenophora) and their successful transplantation into sea anemones (Cnidaria) — which belong to an entirely different phylum — forming extra mouths and pharynxes…!!

Many scientists (including GEITP) believe that comb jellies belong to the earliest branch of the multicellular animal family tree (i.e., earlier than sponges). Kremnyov and his colleagues argue the appearance of an organizer helped transform single-celled organisms into animals.

Graduate student Mangold died tragically in 1924 in a home gas explosion(!!!), but the discovery encouraged her supervisor, Hans Spemann, to perform additional experiments, leading to the 1935 Nobel Prize in Physiology or Medicine. Spemann’s laboratory became the center of the developmental biology world, attracting leading scientists to probe the organizer and look for similar capabilities in other developing tissues (e.g., transplanting tissue from snails and mouse kidneys into frog embryos) showing that these, too, possessed organizational activity. Later, in the 1980s and 1990s, scientists uncovered the molecular basis for organizers: signaling molecules known as morphogens.

Organizer cells and morphogens act like a construction foreman in the developing embryo, telling “the cells what they have to do and what they have to build”. Research into the organizer has been focused mostly on vertebrates. But in 2007, a team led by Technau discovered such cells in the embryos of starlet sea anemones (Nematostella vectensis) [Ref 2, below], which belong to an animal lineage that diverged after that of comb jellies. The findings raised questions about the evolutionary origins of the organizer. Until 2026, it was not known when the organizer emerged.

Kremnyov’s supervisor and study co-author, developmental biologist Andreas Hejnol at the Friedrich Schiller University Jena, maintains a menagerie of unusual invertebrates — including sea anemones, penis worms and flatworms — that he calls a microzoo. When he joined the lab, Kremnyov lab added a comb jelly (Mnemiopsis leidyi). M. leidyi are highly fecund and lay transparent embryos daily. While examining M. leidyi, Kremnyov observed the formation of embryo structures called blastopores — the location of the embryonic organizer in other animals. The structures first arise embryologally during a process called gastrulation, which occurs just a few hours after fertilization in comb jellies.

doi: https://doi.org/10.1038/d41586-026-01910-0

References

1. Kremnyov, S., Lebedeva, T., Genikhovich, G. & Hejnol, A. Nature https://doi.org/10.1038/s41586-026-10643-z (2026). [this pdf article is attached]

2. Kraus, Y., Fritzenwanker, J. H., Genikhovich, G. & Technau, U. Curr. Biol. 17, R874–R876 (2007).

The attached 2026 paper reports that the blastopore lip of the ctenophore Mnemiopsis leidyi, a member of the evolutionary sister group to all other metazoans, exhibits organizer activity. Authors show that transplanted fragments of blastopore lip tissue from M. leidyi gastrula induce secondary pharynx and mouth formation. Moreover, transphyletic transplantation experiments show that the blastopore lip of M. leidyi leads to the generation of a secondary body axis in embryos of the cnidarian Nematostella vectensis. Organizer function in M. leidyi requires both β-catenin and TGFβ signaling, and the TGFβ-family ligands probably provide this inductive capacity. These findings reveal the deep homology of the blastoporal organizer in ctenophores, cnidarians and vertebrates, implying the ancestral organizer role of the blastopore lip. Authors propose that the emergence of the organizer was an essential innovation that facilitated the change from the temporal cell differentiation of unicellular relatives to the spatial cell differentiation of the first multicellular embryo…!! 😊

Does this topic fit our GEITP theme of gene-environment interactions”…?? Yes. 😊 The environmental signal is differentiation; the genetic response is generation of morphogens during early embryogenesis. [Canonical morphogens have been described exclusively in animal systems. The concept was predicted and first named by Alan Turing in 1952]. The first morphogen (Bicoid) was discovered in the Drosophila embryo in 1988 (Driever and Nüsslein-Volhard, 1988).

In high school, yours truly used European earthworms for the annual science fair. He had read (in Scientific American, when it was still a science journal) that earthworms, like newts, can grow a new tail if they lose their tail. He wondered “how far anterior — still qualifies as “tail?” Cutting them into two pieces he found that incision at segment 17-18 — resulted in a variable response: some worms ended up with one head and two tails, others had two heads and one tail, and some had two heads and two tails…!! ☹

It turns out (in retrospect) that the segment 17-18 region was where there is a mixture of morphogens, some telling the animal to create another head and the other telling the animal to create another tail. [Although I had no idea what I had done], my physics and chemistry teachers entered my high school project in the annual Future Scientists of America High School Science Fair (sponsored by the National Science Foundation, Washington, D.C.), where I won First Place in the Biology Division…!! 😊

—DwN

This topic is so mind-boggling and fascinating — that I’d like to send David Nelson’s email blog, just as it was received. Fusarium species are ubiquitous filamentous fungi, found in virtually any soil, in the air, and on plants. They are most commonly associated with cereal crops and grain dust (e.g., rye, barley, corn, oats and buckwheat). CYP621A is a plant cytochrome P450 gene located in Family 621, subfamily A. This fungus can cause human infections.

For those of us who have done genomic DNA sequencing and searching for introns, we know that donor sites and acceptor sites (which are recognized by the spliceosome machinery) are conserved, boundary sequences at the 5′ and 3′ ends of an intron, respectively. These sites guide the spliceosome to excise the intron and ligate the adjacent exons. The donor site (5′ splice site) marks the start of the intron, typically with a GU (in the RNA), or GT (in the DNA) sequence. The acceptor site (3′ splice site) marks the end, usually with an AG sequence.

Some of us have heard of a single triplet codon comprising the entire exon (e.g., GTCGCAG where CGC codes for the amino acid arginine), but the recent publication by David Nelson describes a single nucleotide (GTAAG in which the “A” is located as the middle nucleotide of a triplet codon) that represents the entire exon(!!). Possible reasons for such a genomics structure are discussed in his paper. [For several unusual stories of gene structure and genomics posted each week, you are encouraged to sign up/subscribe at https://substack.com/@davidrnelson] 😊

DwN

This exciting article just came out in Medscape.

DwN

mRNA Vaccines Work Differently Than We Thought (and That’s Good)

Sarah Amandolare

May 25, 2026

Scientists may have been wrong about mRNA vaccines — and they’re thrilled.

While mRNA vaccines are already proven safe and effective, scientists are just now uncovering new details about how they work. A new study finds they can bring about a response by entering nonimmune cells, such as muscle cells, challenging the dogma that mRNA must enter immune cells (dendritic cells) to be effective.

The findings, along with other emerging research, suggest mRNA is more versatile than scientists realized — capable of bypassing traditional immune pathways and using a variety of cells to jump-start the immune system. That understanding could open the door to more effective therapies, with potential implications for hundreds of drugs.

“The assumption for 20 years of my career has been: The secret sauce of mRNA and other nucleic acid vaccines is that they get into dendritic cells,” said senior study author Brian D. Brown, PhD, a professor of genetics and genomic sciences and of immunology and immunotherapy at the Icahn School of Medicine at Mount Sinai in New York City. “That turned out not to be the case.”

mRNA vaccines may work by entering nonimmune cells, like muscle cells, challenging previous beliefs. This discovery suggests mRNA’s versatility, potentially leading to more effective therapies and expanding the understanding of immune responses.

Why Muscle Cells Might Do Some Heavy Lifting

Brown was studying gene therapy in the 1990s when he designed a technology to turn mRNA expression on or off in different cells. For the new mouse study, published in Nature Biotechnology, he adapted the technology to turn off mRNA expression in dendritic cells, muscle cells, or liver cells. The researchers then vaccinated the mice with each version, delivering the vaccines both intravenously and intramuscularly.

photo of Brian D. Brown

Brian D. Brown, PhD

“The results were pretty stunning,” Brown said.

When mRNA expression was turned off in muscle cells, T-cell response went down, suggesting muscle cells play a role in immunity. When expression was turned off in liver cells, T-cell expression tripled — indicating liver cells dampen immunity. Turning off expression in dendritic cells had no effect on T-cell activation, though it did reduce the number of killer T cells by as much as half. (Interestingly, no such reduction occurred when the antigen was SARS-CoV-2 spike. Brown is now investigating why different antigens had varying effects.)

Knowing all this is crucial for designing effective mRNA vaccines and therapies. That’s because different mRNA therapies require different strategies. Cancer vaccines must boost tumor-fighting killer (CD8+) T cells. For genetic disease treatments, scientists want to avoid triggering the immune system to prevent killing the very cells the mRNA is meant to modify.

“Understanding the immunology is extremely important for this class of drug,” Brown said.

The finding doesn’t mean dendritic cells aren’t important for mRNA vaccines to work. “It just means that the mRNA doesn’t have to get into those cells to induce an immune response,” Brown said.

Instead, the antigen can be transferred to those dendritic cells.

Here’s What That Process Might Look Like

Traditional vaccines rely on cross-presentation: Dendritic cells capture a protein or inactivated virus, process it, and display it on MHC class I molecules to alert the immune system. By contrast, mRNA vaccines were thought to require direct presentation, where the mRNA enters a dendritic cell and the antigen is produced and presented by that same cell.

However, Brown’s research suggests that mRNA vaccines may also use cross-presentation. While “the vast majority” of mRNA likely does enter immune cells, Brown speculates that the magic happens when those cells release the newly made antigens into the surrounding tissue. Neighboring dendritic cells then scoop up those free-floating antigens to kick-start the killer T-cell response.

Or a different process entirely could be happening alongside this. Dendritic cells can also trigger a response through “cross-dressing.” That’s when a nonimmune cell (like a muscle cell) processes the mRNA, loading the antigen onto its own MHC. The dendritic cell then snatches the preloaded MHC molecule right off the cell’s surface. In the case of the SARS-CoV-2 spike protein, however, Brown suspects a simpler handoff: The spike protein likely gets cleaved from the muscle cell surface, allowing dendritic cells to vacuum it up and cross-present it.

“It’s a fine finding,” said Kenneth Murphy, MD, PhD, a professor of pathology and immunology at Washington University School of Medicine in St. Louis, who was not involved in the study. “But they didn’t distinguish between what was cross-dressing or cross-presentation.”

Murphy’s recent research published in Nature sheds further light.

‘Everything Is Happening’

Although mRNA cancer vaccines are already being used in clinical settings, very little scientific evaluation of the mechanism exists, Murphy said.

photo of Kenneth Murphy, MD, PhD

Kenneth Murphy, MD, PhD

Scientists have previously assumed that a specific type of dendritic cells — cDC1 — were essential for activating killer T cells to fight viruses or tumors. However, Murphy’s lab discovered that mice lacking these cells still mounted an immune response to mRNA vaccines. Even when researchers stripped all dendritic cells of their MHC class 1 (the part that alerts the immune system), the mice still produced a partial T-cell response.

“You don’t even need [MHC] class 1 to be expressed on a dendritic cell,” Murphy said. “That’s where cross-dressing comes in.” In cross-dressing, nonimmune cells pick up the slack. The nonimmune cell’s MHC transfers to a dendritic cell, which then presents it to the T cell.

“The subtlety in our paper is that everything’s happening,” Murphy said — direct presentation, cross-presentation, and cross-dressing.

Expanding the mRNA Landscape

Murphy also captured a gene expression signature for individual killer T cells in wild type mice and mice with only cDC1s or cDC2s. There were differences depending on which dendritic cell did the priming, with cDC1s driving a stronger killer T-cell response.

“If you’re going to try to optimize a CD8+ T-cell response to a neoantigen in a cancer setting, you might want to understand how the antigens are being processed and what dendritic cell is presenting them,” Murphy said.

His mouse models are available in The Jackson Laboratory database, which vaccine and therapeutic developers can use “to see whether or not their antigens are cDC1 processed or cDC2 processed or both, or cross-dressed, or something else,” Murphy said.

How mRNA vaccines spur development of helper (CD4+) T cells is also under investigation. Research published in Nature Communications in January found that mRNA vaccines are better at activating helper T cells through direct presentation. The researchers’ previous flu research in 2015 suggests that some helper T cells can only be activated by direct presentation.

photo of Ike Eisenlohr

Laurence “Ike” Eisenlohr, VMD, PhD

“It is an important consideration,” said senior study author Laurence “Ike” Eisenlohr, VMD, PhD, a professor of pathology and laboratory medicine at Children’s Hospital of Philadelphia Research Institute in Philadelphia. “It’s safe to say that all three papers” — his, Brown’s, and Murphy’s — “point to an expanded landscape of antigen processing and presentation when it comes to mRNA-based vaccines.”

Yet scientists have likely only scratched the surface of the biological foundations of mRNA. “We looked at three different types of cells,” Brown said. “We can go much, much more granular.”

Brown reported being on the scientific advisory boards of Noetik, Asgard Therapeutics, and Navexio. Murphy and Eisenlohr had no relevant disclosures.

These stories (from Korean high school students) are heartwarming and exactly the kind of response that we on the CO2 Coalition Education Committee like to see. 😊😊

—D

From: Greg Wrightstone
Sent: Thursday, May 28, 2026 1:12 PM
To:
Subject: Korean presentation

As I mentioned this morning in the Ed Meeting, Dr. Park has translated “Inconvenient Facts” into Korean and provided free copies to a high school Book club. He and I are presenting it in the wee hours tomorrow morning in Seoul, S Korea. Several book reports are shared below and confirm what I have been saying for many years. Once people are exposed to the truth, minds change quickly.

1.

Hello. My name is So-won Choi, and I am a senior student at Daejeon Imun High School in South Korea. It is truly an honor for me to meet both Mr. Gregory Wrightstone, the author of *Inconvenient Facts*, and Professor Park Seok-soon, who translated this book into Korean, at such a meaningful event today.

Until recently, I had accepted the media’s message about a climate catastrophe without much doubt. Whenever I saw images of melting glaciers and suffering polar bears, I often felt a vague sense of fear and anxiety about the future of our planet.

That is why reading *Inconvenient Facts* was such a huge intellectual shock for me. The objective data presented in the book — such as the 350-year temperature record of Central England, and the statistics showing actual decreases in droughts and wildfires — completely challenged many ideas that I had previously believed to be unquestionable truths.

To be honest, while reading the book, especially the epilogue suggesting that “doing nothing” could sometimes be the right policy, I felt confused and even resistant because it was so different from the mainstream narratives I had always heard.

However, through these “inconvenient facts,” I learned a very valuable lesson. I realized that we can approach the truth only when we face scientific facts directly, rather than being swept away by emotional persuasion or public fear. I deeply appreciate the insight and courage of both of you for compiling and presenting such a vast amount of data that challenges widely accepted assumptions.

Lastly, I would like to ask Mr. Wrightstone one question.

In today’s world, many media outlets and political groups often amplify fear about climate change, and people who speak differently are sometimes criticized as “climate change deniers” and face strong social pressure. Even so, you continue to speak publicly about what you believe to be scientific truth.

Where does that courage and motivation come from?

Thank you very much.

2.

Hello, my name is Jeong Eun-gyo, and I am a senior at Daejeon Imun High School.

Today, I would like to briefly share my thoughts and reflections after reading Inconvenient Facts.

What I felt most strongly while reading this book was that I had accepted many environmental issues and climate-related messages from the media as unquestionable truths without much doubt or critical thinking. However, this book made me realize that many of the ideas we are familiar with should be reexamined through scientific data and objective evidence.

At first, some of the arguments presented in the book felt unfamiliar and, as the title suggests, somewhat “inconvenient.” For example, I had always believed that increasing carbon dioxide naturally leads to rising temperatures and accelerated climate change, and therefore must be entirely negative.

Yet I realized something ironic about my own attitude. I had rarely questioned the beliefs I had previously accepted, but when I encountered the “inconvenient facts” presented in this book together with scientific data and evidence, I immediately began to question them.

This experience became an opportunity for me to reflect deeply on my own way of thinking. I realized that when information different from what I had previously believed was presented to me, I may have unconsciously doubted or avoided it rather than carefully examining it. Perhaps I had not even made a genuine effort to face such facts in the first place.

Through this book, I came to understand how easily people can become biased toward information that feels familiar and comfortable to them. I also realized that I myself am not free from such bias.

After reading this book, I felt that I should develop a more critical attitude toward the climate crisis narratives emphasized in the media by examining the evidence and reasoning behind them for myself. Furthermore, I believe our society should not dismiss certain facts simply because they differ from widely accepted beliefs, but instead face them honestly through valid scientific evidence and open discussion.

I hope that, through such efforts, these “inconvenient facts” may eventually become facts that everyone is willing to recognize and consider.

Lastly, I would like to ask one question.

Among the many “inconvenient facts” discussed in your book, which issue do you believe our society should pay the most urgent attention to today?

Thank you very much.

3.

Hello. My name is Chae Jeongwon, and I am a senior at Daejeon Imun High School. I am truly grateful for the opportunity to attend today’s lecture on Inconvenient Facts: The Science That Al Gore Doesn’t Want You to Know. It was especially meaningful to hear from both the author, Gregory Wrightstone, and the translator, Professor Park Seok-soon.

Through this lecture, I was able to reflect once again on my own views about climate change. Until now, I had simply regarded climate change as a serious environmental problem. However, I found it very interesting that this book explains climate change from a different perspective than the one we are generally familiar with.

In particular, I was impressed by how the lecture encouraged us to reconsider common assumptions about carbon dioxide and climate-related disasters. I also found it interesting that phenomena such as wildfires and typhoons can be viewed from various scientific perspectives.

This lecture helped me realize the importance of understanding climate change through multiple viewpoints rather than accepting only one perspective or opinion.

Lastly, I would like to ask one question. What is the most important message or idea that you hoped readers would take away from this book?

Thank you very much.

Gregory R. Wrightstone

Senior Fellow

CO2 Coalition

2677 Prosperity Avenue, Suite 300

Fairfax, VA 22031

(703) 540-4700

wrightstone@co2coalition.org

Website: https://co2coalition.org/

Image

Our CO2 Coalition Education Committee sets up a booth that is manned by between 4 and 6 CCEC members — at about six or eight homeschooling state conferences each year. Attendance is always between 10,000 and 20,000 parents and children…!! I’ve been repeatedly invited but am not healthy enough to attend these conferences all over the country between March and October… ☹☹

Angela Wheeler has recently become our Executive Director. She is one heckuva dynamic woman: married with six children (all girls) and is leader at all these homeschooling conferences each year since 2019. ☹😊

—D

This article about “fraud in science” was submitted from a GEITP’er who also reads (of all things) the South China Morning Post… Note that some of Fred’s favorite journals are listed as those in which fraudulent manuscripts have unfortunately been reviewed and published. ☹☹

DwN

Chinese scientists vacate their positions after whistle-blower raises alarms over their research

Trio faces heightened scrutiny after a former doctoral student and blogger (known as Student Geng) raised questions about their work

Science blogger Student Geng raised questions about the quality of their work. Photo: Bilibili

By Shi Huang

Published: 31 May 2026

Three more senior Chinese scientists have been disciplined by their universities after a high-profile blogger raised red flags about their research.

Nankai University in Tianjin announced on Saturday that Chen Quan had been removed as Dean of its College of Life Sciences. The university said that Chen, as a corresponding author, failed to properly oversee the quality and authenticity of experimental data in a paper published in Nature Cancer in 2024.

Meanwhile, Sun Yat-sen University in Guangzhou said Kang Tiebang had been removed as Deputy Director of the State Key Laboratory of Oncology in South China, and Kuang Dongming was no longer Associate Dean of its School of Life Sciences.

The university said Kang was the corresponding author for a paper published in Nature Cell Biology in 2020 that had various data and image errors. Kuang was accused of similar misconduct associated with three papers published in Nature Cell Biology, Science Advances, and Cell.

The announcements came three weeks after Tongji University in Shanghai said it had removed Wang Ping, a leading cancer researcher, as Head of its School of Life Sciences over academic misconduct related to research papers.

All four researchers had been given the national “outstanding youth” award – an honour that is considered a prerequisite for admission to China’s top science and engineering academies.

But they faced increasing scrutiny after a former doctoral student turned blogger and video creator known as Student Geng raised questions about their research.

Geng, a former biomedical engineer, used AI tools and statistical methods to identify data anomalies in work by a long list of leading researchers.

Geng’s videos about his findings have attracted 1.8 million followers on social media.

(From left to right) Chen Quan, Kang Tiebang and Kuang Dongming. Photo: Handout

(From left to right) Chen Quan, Kang Tiebang, and Kuang Dongming.

Geng’s video about Wang examined data anomalies in a paper published in the journal Nature.

Other prominent targets of his videos include Central South University’s Xiangya School of Medicine, East China Normal University, and Hunan University.

Geng was profiled last week by the state news agency Xinhua in two articles published on social media that praised his high expectations about research quality and the positive impact of his work in popularizing science. It said he was angered by academic fraud but warned he “could not replace the system”, adding that the problem should be tackled within universities and research organizations — rather than on social media. In a later video, Geng said the attention made him feel like a “child who has a desire to be recognized and is suddenly being praised by their parents.”

But not all the attention he attracted was so welcome. On Friday, he said in a status update that his main channel on Douyin, the Chinese version of TikTok, had been permanently restricted following an undisclosed complaint, meaning he could not earn revenue from his videos.

Nankai University told Xinhua it would learn lessons from the case and “comprehensively reinforce education on research integrity, and build a clean and upright research environment and academic atmosphere.”

Sun Yat-sen University also told the news agency it would strengthen its oversight systems.

Springer Nature, which publishes several of the journals where the research appeared, has been asked for comment, as have the publishers of Science Advances and Cell.

In response to a previous report about Geng’s whistle-blowing, Springer Nature’s head of communications Michael Stacey told the South China Morning Post that the publisher “was undertaking a rigorous investigation” and would “take any appropriate action in line with our policies to protect the integrity of the scientific record.”

Lucia:

In response to your request.

This manuscript [see attached] is now “in press” and should appear online within the week. I’m VERY proud of this one. Knowing next-to-nothing about [a] the ‘nuts and bolts’ of bioinformatics programs and [b] lipid chemistry in vitro — I’ve spent since last July educating myself on these two topics, and then I used two previous GEITP email blogs as a foundation for writing this up.

Of course, despite two coauthors (helping me with EndNote and graphic illustrations), I wrote every word of the text and found all the references myself etc. What amazes me the most is the “overwhelming (divine?) Force” — to create Life as early as possible, despite a very inclement environment on early Earth. ☹☹

Remember we both sat in on that course (around 2009?) by Dr Rao on Bayesian mathematics…?? I thought the course was very useful and I’m glad you talked me into it. 😊 Bayesian math refers to a framework of statistics based on Bayes’ Theorem. It treats probability as a measure of belief or confidence rather than just long-run frequencies. It is unique because it allows you to continuously update your predictions as new evidence becomes available. Also, if some “important data points” are unavailable, Bayesian math is able to “insert the most likely numbers statistically” into those positions.

My main challenge was to “bring this paper down to a level” that I can understand, and that the Human Genomics Readership might also understand… ☹😊

—Dan

WHO said “you can’t teach an Old Dawg (VERY old dawg) — new tricks”…??????????

Heat shock proteins (HSPs) are a family of highly conserved proteins produced by cells in response to stressful conditions, such as extreme heat, cold, or toxicants. They ae present in organisms from bacteria to all animals. They primarily act as “molecular chaperones,” stabilizing new proteins to ensure that they fold correctly and either refold proteins that have been damaged by stress (or remove damaged proteins from the cell).

Around 1970, I recall that an NIH Institute Director asked me “What is the reason for HSPs to exist in humans?” My answer then was “We don’t know now, but someday we’ll understand the reason why Mother Nature has added these genes encoding HSPs to the human genome.” 😊

DwN

17 June 2026

These ‘master’ proteins protect us from deadly mutations — and could inspire new drugs

Biology has clever ways to mask the effects of potentially harmful gene mutations. Scientists are investigating how this ‘buffering’ works — and how to exploit it.

By Philip Ball

Conceptual illustration of a DNA bomb with a lighted fuse being extinguished by two pinching fingers.

Our genomes are full of mutations that have the potential to damage our health or even kill us. Yet most of them rarely cause problems. Why?

It’s partly thanks to a family of proteins that mask, or ‘buffer’, the ill effects that these mutations would otherwise unleash. This buffering might help to explain why gene variants cause disease in some people but seem to have limited or no impact on others. It could also underlie how some cancer cells and pathogens threaten their hosts and evade drugs. And it enables genetic variation to accumulate in populations, providing a potential resource for future evolution.

Researchers have known for decades that one of the most important factors in mutational buffering is a protein called HSP90 and its family of other HSP proteins. Now, biologists are examining the roles of these proteins in more detail than they ever could before, owing to advances in techniques such as cell screening and genetic editing, as well as the availability of large genomic data sets and extensive health records.

Advances in the past two decades or so have “shifted our view on HSP90 buffering as a theoretical idea to one with immediate and important practical applications, especially in the clinic”, says geneticist Georgios Karras at the University of Texas MD Anderson Cancer Center in Houston. HSP90, for instance, might mediate the risks of breast cancer linked to the BRCA1 gene in some individuals. Some drugs that target buffering proteins are already being developed.

Researchers have long suspected that these proteins might influence the course of evolution, and results from the past several years have strengthened that notion. By ensuring that organisms can thrive despite harboring risky gene mutations, buffering proteins build up a pool of variation that can be released in the face of environmental stress, triggering the rapid emergence of new adaptations. In this way, says Karras, HSP90 has probably “shaped adaptive evolution of life on Earth”.

Folding assistants

In the 1950s, biologist Conrad Waddington wanted to study how an animal’s environment affected its physical traits. He kept some fruit fly pupae at 40 °C for a few hours — a much higher temperature than the pupae would normally experience. Waddington saw that this heat-shock treatment had induced new wing shapes in some of the resulting flies. By selectively breeding flies with abnormal wings, the mutant phenotypes eventually appeared even without the heat treatment 1. They had become genetically fixed. This suggested that the genetic variation underlying these phenotypes was already present in fly populations but was somehow hidden until the heat treatment revealed it.

Waddington’s work puzzled his contemporaries. It didn’t seem to fit with the prevailing view of how genes give rise to inherited traits. Independent work in the following decades identified genes that were switched on by heat exposure; the proteins produced by these genes became known as heat-shock proteins (HSPs).

Then, in 1998, molecular biologists Suzanne Rutherford and Susan Lindquist, at the time based at the University of Chicago in Illinois, linked the activity of these proteins to the strange effects that Waddington had seen. They bred fruit flies from standard laboratory strains with flies that carried mutations of a gene called Hsp83 (the fly equivalent of HSP90 in humans) 2. About 1.7% of the cross-bred strains had developmental defects, including deformed abdomens, no eyes and misshapen legs and wings. Why did a single genetic mutation produce such a wide range of changes?

The researchers concluded that there must be a latent pool of mutations in the normal fly population, and they had found the master switch that unleashed them all. Lindquist thought that the HSP90 protein acts as a “capacitor for morphological evolution”, keeping genetic variation hidden. Turn it off, and all hell can break loose 2.

Because organisms can’t be too sensitive to mutations if they are to be viable at all, various forms of buffering are woven into the complex networks formed by genes and their interactions, says genomicist Christine Queitsch at the University of Washington School of Medicine in Seattle. For example, pathways can be reinforced by having a backup if one fails. Buffering can also involve more complex reshuffling of genes’ duties in ways that are still not fully understood: feedback loops, for example, that boost the activity of one gene to compensate for the failures of another.

Since Lindquist’s groundbreaking work, HSP90 and the wider family of HSP proteins have emerged as key components in buffering mechanisms. These heat-defense proteins are found in organisms ranging from bacteria to humans. High temperatures can cause many proteins to denature and lose their functional folded structure. HSP90 is a ‘molecular chaperone’ that helps denatured proteins to refold (see ‘Folding facilitators’). There is a lot of it in cells: it comprises about 1% of the total protein content of human cells.

Folding facilitators: Three-panel diagram showing protein folding outcomes: normal folding without chaperones, correct folding of a mutated protein aided by HSP90 chaperone, and misfolding when the chaperone is inhibited by a drug.

HSP90 helps to fold a wide range of ‘client’ proteins, many of which sit at the heart of important processes. These include hormone receptors, transcription factors and cell-signaling molecules. It’s now clear that HSP90 isn’t just helping to protect against heat shock — it is also keeping its client proteins functional under normal conditions in the face of mutations that might otherwise impair their folding.

But there are limits to how much stress HSP90 can cope with. It can be overpowered by demand in times of stress, and unable to contain genetic variation. That’s not necessarily a bad thing, because some genetic variants might confer advantages in some organisms — phenotypes that can help a population to deal with the stress. These variants might then become dominant in the population through selection.

HSP90 is not alone. Work in the past few years has identified several more relevant genes outside the HSP family. In 2024, Kevin Verstrepen, a geneticist at the VIB-KU Leuven Center for Microbiology in Belgium, and his co-workers used a high-throughput technique to identify buffer genes in the yeast Saccharomyces cerevisiae 3. They took around 5,000 strains, each with a different gene deleted, and then used ultraviolet light to induce more mutations at random. If the deleted gene was involved in buffering, you would expect to see more variation in growth or other characteristics when the cells are exposed to UV.

The study identified a handful of genes with strong effects of this sort, all of which are involved in protein folding (similar to HSP90) or in organizing chromatin, the DNA–protein complex that forms chromosomes. But Verstrepen says that what constitutes a buffering gene is up for debate: many, if not most, genes interact with others. “There is no clear definition of the magnitude of genetic interactions that a gene must have before we call it a buffer gene”, says Verstrepen. “It is a bit of an arbitrary cut-off.”

Buffering in disease

HSP90 remains the poster child of the field, however. That, says Queitsch, is because it is so sensitive to stresses — it plays an important part linking an organism’s biology to its environment — and because its client proteins have such important roles in shaping phenotypes. If there are problems with HSP90, defective gene variants or random mutations that occur constantly in our cells, especially when we are exposed to stresses such as UV light, alcohol and cigarette smoke, can emerge in ways that might be problematic. “If someone lacks a buffer gene, or has a buffer gene with lower activity, that person may be more susceptible to the effects of new, random or already present mutations,” says Verstrepen.

This is why buffering is becoming a focus of biomedical research. In 2017, Karras was a postdoc in Lindquist’s lab when the team first identified a role for two buffering proteins, HSP90 and HSP70, in human health 4. (Lindquist was a co-author of the paper but she had died from cancer the year before.) The researchers looked at the buffering of FANC proteins, which are involved in repairing damaged DNA. Mutations in the genes that code for these proteins are associated with the rare disease Fanconi anaemia, which can lead to developmental complications as well as a predisposition to cancer. Karras and his colleagues found that HSP90 buffers some variants of one such gene, called FANCA (the role of HSP70 is more complex).

They also tested the effects of compromising HSP90 in cells. When subjected to temperatures of 39–40 °C (in the range that might be experienced by someone with a fever), the cells became more vulnerable to DNA damage caused by chemical compounds. The researchers determined that the HSP90 reservoir is exhausted by the demands created by the heat stress, so that it can no longer mask FANCA mutations.

One implication of the work, says Karras, is that the effects of particular disease-linked gene variants could depend on environmental stressors such as temperature, which can alter the degree of buffering. The researchers have yet to study this possibility.

A 3D illustration of the molecular model of the human heat shock protein Hsp90, showing softly glowing structures composed of tightly packed spherical units in purple, pink, blue and teal against a black background

The protein HSP90 acts as a buffer against gene mutations, helping proteins made from mutated genes to fold correctly, and neutralizing the effects of such variants.

If environmental stress can indeed affect disease risk from gene variants, it would complicate efforts to estimate such risk from genetic analysis alone. What’s more, the clinical implications of a mutation are also muddied by complex interactions with other genes, making it even harder to establish how much a given variant might impact someone’s risk of disease — i.e., its ‘penetrance’.

Although Fanconi anemia is a rare condition, the same considerations should apply to more common genetic disease variants. Karras has been investigating the buffering effects of HSP90 on the BRCA1 gene. Similar to the FANCA gene, BRCA1 is involved in genome maintenance, and HSP90 stabilizes mutant variants and helps them to perform their functions. This lowers the chances of developing breast cancer early in life for people who carry these variants 5. The age-related cancer risk seems to depend on the extent to which the BRCA1 proteins bind to HSP70 and HSP90 6. Compromise HSP90, and the problems associated with those variants are revealed — although the extent to which this is happening in BRCA1-associated cancers isn’t yet known, says Karras.

Nature 654: 586-588 (2026) doi: https://doi.org/10.1038/d41586-026-01883-0

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