If intelligent design advocates were honest enough to follow the logic of their own arguments and apply it consistently to the real world, they ought to be acutely embarrassed by the deity they are presenting to the public. Their putative designer god, judged by the evidence they themselves cite, looks less like a benevolent engineer and more like the author of suffering, disease, and death.
That uncomfortable reality is illustrated by yet another research paper showing that pain and mortality can be the direct result of the very things ID proponents celebrate as hallmarks of design: irreducible complexity and “complex specified information”.
This latest example comes from scientists at Nagoya University, Japan, who have shown how ovarian cancer forms an alliance with healthy cells that enables it to spread rapidly to other organs in the abdomen. Their paper has just been published in Science Advances.
As regular readers will be aware, a recurring theme of this blog is that ID advocates conspicuously ignore the vast number of examples from parasitology, oncology, and genetics where the very evidence they cite for an intelligent designer applies just as readily to diseases caused by parasites, pathogens, and genetic malfunctions. Applying ID’s own logic, these are not signs of benevolent craftsmanship but evidence of something far darker — a malevolent intent behind the supposed designer.
The paper in Science Advances is yet another case in point, and doubtless there will be many more soon.
The authors discovered that ovarian cancer cells gather clusters of mesothelial cells from the peritoneum and form hybrid spheres. These protect the cancer cells, help them invade other organs, and create a pathway for metastasis throughout the abdomen. Worse still, these hybrid spheres resist chemotherapy more effectively than cancer cells alone.
If something this complex resulted in something beneficial for humans, Discovery Institute fellows Michael J. Behe and William A. Dembski would doubtless have produced one or more books about it, written magazine articles, and embarked on television tours explaining how the finding devastates “Darwinism” and constitutes scientific proof of an intelligent designer — leaving their audiences in no doubt that the locally favoured god is the only entity capable of producing such complexity.
As it is, we can expect only a deafening silence from the Discovery Institute, while their hapless supporters cast about for a fundamentalist religious excuse such as “the Fall”, or perhaps invoke some other evil agent — anything, in fact, except the god of the Bible, who is apparently only credited with designing good things.
Researchers from the Hebrew University of Jerusalem have uncovered yet another layer of exquisite molecular sophistication in one of humanity’s most persistent and lethal parasites, Plasmodium falciparum, the chief cause of malignant malaria. Their findings, reported in a recent press release and published in the peer-reviewed Journal of Cell Biology, describe a newly identified regulatory “crown” checkpoint that controls parasite reproduction with remarkable precision.
It is difficult to imagine a discovery more awkward for Intelligent Design creationists, because Plasmodium falciparum is precisely the sort of organism that embodies everything Michael Behe and William Dembski insist cannot arise by evolution. Here is complex specified genetic information, tightly regulated developmental choreography, and interlocking biochemical machinery operating across multiple life stages — the very definition, we are told, of “irreducible complexity”.
Unfortunately for the Discovery Institute, this irreducible complexity does not produce a bird’s wing, a human eye, or some uplifting example of divine craftsmanship. It produces malaria — a parasite responsible for immense suffering and hundreds of thousands of deaths every year, mostly children. If complexity is meant to be a hallmark of intelligent design, then the designer’s portfolio includes some rather grim specialities.
The problem is compounded by the fact that Michael Behe has already made malaria central to his arguments. In The Edge of Evolution, he famously pointed to the parasite’s resistance to anti-malarial drugs as an example of the supposed limits of Darwinian evolution, claiming that multiple coordinated mutations were beyond the reach of natural selection. Yet malaria has since become one of the clearest demonstrations that evolution not only occurs, but does so rapidly and repeatedly, exploiting enormous population sizes and intense selection pressures to produce exactly the adaptations Behe claimed were improbable.
As Kenneth Miller pointed out, Behe's mathematical sleight of hand was to assume resistance had to evolve as a single event in a single cell, not across a large population over time - a fallacy of which any good microbiologists should have been aware.
This newly described “crown” stage is simply the latest reminder that biological complexity is not evidence of supernatural design. Evolution predicts complexity wherever it confers survival advantage — including in parasites, pathogens, and diseases. The only real surprise is that creationists continue to present complexity as a theological virtue, when nature so often deploys it in the service of exploitation rather than benevolence.
As ever, none of this will deter creationists from repeating their familiar articles of faith. Faced with an organism whose life cycle resembles a biochemical symphony — regulated checkpoints, specialised invasion machinery, host-cell remodelling, immune evasion, and reproductive stages split between mosquito and human — they will insist that this is not evidence for evolution but evidence against it. The argument, such as it is, runs that complexity must have been present from the start, because it could not have arisen gradually.
But this is simply the old “irreducible complexity” claim in a new disguise: the assertion that because creationists personally cannot imagine intermediate stages, no such stages could have existed. Science, of course, is not obliged to conform to the limits of anyone’s imagination. Evolution does not require that complex systems appear in a single leap. It proceeds by modification of what already exists — co-option, duplication, repurposing, and incremental refinement over deep time — producing the layered complexity we observe today.
Another common retreat is the insistence that this is merely “microevolution”, the trivial shuffling of genes within some mythical created “kind”. Yet Plasmodium falciparum is not merely adjusting the colour of its spots. It is evolving novel biochemical strategies, repeatedly acquiring drug resistance, fine-tuning developmental regulation, and exploiting host environments with extraordinary efficiency. If this is “only microevolution”, then the term has been drained of all meaning.
paper just published in Emerging Infectious Diseases by a team led by Nischay Mishra, of the Columbia University Mailman School of Public Health, shows that Pteropine orthoreovirus (PRV) — a bat-borne orthoreovirus — has crossed the species barrier into humans in Bangladesh, causing a Nipah-like illness that is difficult to distinguish clinically from Nipah virus infection. The disease presents primarily as an acute respiratory infection, sometimes accompanied by encephalitis.
It has long been known that bats possess a markedly more effective antiviral immune system than humans. This fact alone presents a problem for creationists who insist that humans — and, conveniently, themselves — are the special creation of an omnibenevolent deity. There is no coherent reason why such a deity would equip bats with a superior immune system while leaving humans comparatively vulnerable, unless the intention were for humans to suffer more infectious disease than is strictly necessary.
However, the bat immune system appears to have a significant evolutionary trade-off. Rather than eliminating viruses entirely, it often suppresses their pathological effects while allowing persistent infection. As a result, bats function as biological incubators in which viruses can circulate, diversify, and evolve. Inevitably, some of these variants acquire the ability to cross species barriers and infect humans. This remains the most parsimonious explanation for the emergence of SARS-CoV-2, the virus responsible for COVID-19 — the pandemic of 2020–2022 that killed tens of millions of people and inflicted severe damage on the global economy.
Creationists argue that complex, specified genetic information must be supplied by their putative intelligent designer and then, by a glaring act of circular reasoning, claim that the mere existence of such information constitutes evidence for that designer. This line of argument has no more merit than insisting that tins of baked beans can only be made by magic pixies, and therefore that the existence of tins of baked beans proves the existence of magic pixies. It is a form of reasoning that functions only for those who lack even a basic grasp of logic.
An additional difficulty for creationists is that PRV could only become infectious to humans if it possessed the precise genetic features required for that capability. Within the internal logic of intelligent design apologetics, the zoonotic PRV must therefore count as the product of deliberate design — and hence as evidence for a malevolent intelligent designer. The usual response is to abandon any pretence that intelligent design is science rather than religion in disguise, and to retreat into Christian fundamentalism, invoking “the Fall” and claiming that some other supernatural entity was empowered to interfere with creation and design its own suite of pathogens and parasites. This claim borders on blasphemy even within Christian theology, which traditionally reserves the creation of living things exclusively to their deity.
A paper just published in Molecular and Cellular Endocrinology shows how precisely the sort of complex specified information and irreducible complexity that Discovery Institute fellows William A. Dembski and Michael J. Behe proclaim as evidence of intelligent design can instead combine to ensure that pancreatic cancer survives, metastasises, and ultimately kills its victims.
This, of course, is true of many diseases, which simply would not exist unless the right combination of genetic information were present and functioning correctly for the disease itself. Yet creationists routinely compartmentalise their beliefs so that harmful “designs” are excluded and blamed on something else, while only those features that appear to benefit humans are credited to a designer.
In the case of parasites, what is harmful to humans is often beneficial to the parasite, but once again the presence of harm causes the logic of creationist arguments to shift. No longer is this evidence of intelligent design, but of something called “sin”, which appears to operate as an autonomous entity capable not only of corrupting creation but of designing living organisms and manipulating their genomes. The formerly omnipotent, omnibenevolent and omniscient designer god now seems strangely impotent, indolent, or indifferent in the face of this alternative “designer”.
This theology also sits uncomfortably alongside another core fundamentalist belief: that God has a plan for everyone, and that everything that happens in a person’s life occurs as part of this divine plan. Presumably, then, that plan must include any diseases they suffer from, including cancer.
It is therefore difficult to see how creationists can escape the conclusion that their god designs and causes cancer as part of this plan, while continuing to cling to the claim that intelligent design is inherently benevolent.
Researchers from Goethe University, Frankfurt am Main, Germany, have shown how a faulty DNA repair mechanism triggers inflammation and leads to accelerated ageing, developmental abnormalities, and cancer.
Their findings are published in Science.
As I explained in my book, The Unintelligent Designer: Exposing the Intelligent Design Hoax, one of the hallmarks of an evolved system — and one which creationists have been conditioned to mistake for evidence of intelligent design — is complexity. In reality, the opposite is true: intelligently designed objects and processes are typically *minimally
complex, doing exactly what is required and no more.
One reason complexity arises in evolved systems is the need for additional layers of processes to compensate for the suboptimal designs that evolution inevitably produces. An intelligently designed process — especially one devised by a designer endowed with foresight — would require no such compensatory mechanisms. It would function reliably every time and be robust enough to withstand environmental stressors and other causes of malfunction. Nor would a perfectly designed copying process be prone to copying errors.
What we observe in reality, however, is an excessively complex system that still malfunctions — and when it does, it can do so unpredictably and catastrophically, leading to increased suffering and even death. The equivalent, in engineering terms, would be an aircraft manufacturer producing planes that were mostly safe most of the time, yet costly to build because they relied on intricate back-up systems to compensate for other components prone to failure — and which nevertheless suffered unpredictable mid-flight failures when those back-ups failed, causing aircraft to fall from the sky. Such an incompetent aircraft manufacturer would not remain in business for long.
In contrast to evolved systems which are overly complex and still prone to errors, an intelligently designed organism would be minimally complex, maximally efficient, robust enough to withstand environmental stressors and work perfectly every time. As so often, what ID predicts is not what we actually observe. In normal science, the falsification of a hypothesis is regarded as confirmation that the hypothesis was wrong, but in creationism the reverse holds; if the facts fail to confirm the hypothesis the facts must be wrong. The hypothesis must be clung to with grim determination, come what may.
A) Toxoplasma gondii tachyzoites, the rapidly multiplying form of the parasite. B) A bradyzoite cyst containing Toxoplasma gondii within a muscle fiber, showing the cyst wall and individual bradyzoites. C) Histological section of tissue with Toxoplasma gondii cysts. D) Microscopic image of a Toxoplasma gondii oocyst, responsible for environmental transmission.
Another example of a nasty little parasite that bears all the hallmarks of the Discovery Institute’s supposed *“proof”* of intelligent design was unveiled today, when scientists from the University of California, Riverside published the results of their investigation into the common brain parasite, Toxoplasma gondii, which infects up to a third of the global population. Their paper was published open access in Nature Communications. It has been released unedited to provide early access to the findings.
Ask Discovery Institute (DI) fellow Michael J. Behe for proof of intelligent design and he will produce multiple examples of what he terms “irreducible complexity”, claiming that such systems could not have evolved step by step and therefore must have been designed by a supernatural intelligent designer. Similarly, ask another DI fellow, William A. Dembski, for proof of intelligent design and he will produce examples of what he calls “complex specified genetic information”, which he claims likewise could not have evolved naturally and therefore must have been provided by a supernatural designer.
Curiously, however, when biologists point to examples of “irreducible complexity” or “complex specified genetic information” in pathogens or parasites — organisms whose sole apparent purpose is to make us ill or kill us, or at the very least to increase suffering in the world - as evidence that, if the ID creationists’ argument were granted, it would imply malevolent intent on the part of the intelligent designer, the response is either silence or retreat into theology. More often than not, the blame is shifted to “the Fall”, while the insistence remains that intelligent design is a genuine scientific alternative to “Darwinism”, and not merely Bible-literalist Christian fundamentalism under another name.
At this point, their supposed “proof” of intelligent design quietly evaporates. Behe will even attempt to argue that the random process he calls “genetic entropy” is responsible, thereby conceding that random processes can generate what Dembski describes as complex specified genetic information — while simultaneously insisting that such information cannot have evolved through random processes at all.
The UC Riverside team have now shown that Toxoplasma gondii is even more complex than previously thought. It was already known that the parasite invades the brain and other tissues, where it forms dormant cysts that can later be reactivated. Its preferred hosts are members of the cat family, and humans are most commonly infected via cats. In some secondary hosts, it has been shown to manipulate behaviour in ways that make them more likely to be eaten by a cat, thereby completing its life cycle. Infected mice, for example, actively seek out the presence of domestic cats, while chimpanzees develop a fascination with the scent of leopard urine. It is possible that effects observed in humans are an echo of this behaviour-modifying mechanism inherited from our evolutionary past.
The new research shows that these cysts are far more complex than simple dormant copies of the parasite. Instead, they are intricate assemblages of multiple sub-types, each with distinct biological functions. In this respect, the cyst exhibits some of the characteristics of a multicellular organism, including a degree of cellular specialisation.
In a recent paper published in Biocontaminant, a group of environmental and public health scientists from China and the United States warn of the growing threat to public health from a group of dangerous free-living single-celled amoebae, the most notorious of which is Naegleria fowleri, also known as the brain-eating amoeba.
This complex, eukaryotic organism bears all the hallmarks of what Discovery Institute fellows William A. Dembski and Michael J. Behe insist is compelling evidence for intelligent design — complex specified genetic information and irreducible complexity — so, if we accept their argument, we have to conclude that whatever designer they imagine is doing this designing must also be the one who designed these nasty little ways to make people sick and die by having their brains eaten, like in some grotesque zombie apocalypse.
N. fowleri normally lives in soil and water, where it feeds on bacteria and other micro-organisms, but if it manages to get into a victim’s nose it can track along the olfactory nerves to the brain, where it treats brain cells the way it treats soil-borne organisms and sets about eating them. Infections are almost invariably fatal. What makes them particularly dangerous is their ability to survive extreme conditions that would kill most micro-organisms, such as high temperatures and strong disinfectants like chlorine, so they can persist in water supplies that most people regard as safe.
An additional hazard is that these amoebae can also act as carriers for other pathogens such as Legionella pneumophila, Chlamydia, and Mycobacterium tuberculosis. By providing these pathogens with protection from disinfection, the amoeba can enhance their pathogenicity and prolong their survival in the environment.
It would be hard to find a better example than N. fowleri of what creationists insist must be intelligently designed, so it follows that there are probably few better examples of the sheer malevolent evil of any designer of such creatures, from the perspective of the humans infected with it. For creationists to retreat into the traditional excuse of blaming ‘the Fall’ is to abandon the claim that irreducible complexity and complex specified genetic information are definitive evidence of intelligent design, and to retreat instead into religious fundamentalism and Bible literalism.
You might expect an intelligently designed system, created by an omnibenevolent designer, to work just as effectively for everybody and not badly for some and only just adequately for others. And yet, as so often with creationism, the facts are not at all what the theory predicts. In science this would be called falsification, but for creationists it is just another inconvenient fact to be ignored or blamed on ‘the Fall’ — or even on the victim.
According to a paper just published in Cell Press Blue, the reason some people suffer more from a cold caused by a rhinovirus is not so much because of differences in the virus, but because their bodies react differently. Some take control and prevent the spread of viruses to adjacent cells of the mucous membrane lining the nasal passages, whereas other people’s bodies fail to prevent the virus spreading.
The paper is by a team at Yale School of Medicine, New Haven, CT, USA, led by Associate Professor Dr Ellen F. Foxman, PhD.
By growing organoids in vitro and infecting them with rhinoviruses, the team were able to show that whether the infection spreads depends on how quickly the infected cells are able to mount an interferon response. A good response limits the infection to just a few cells and the cold does not develop beyond a ‘sniffle’. Where the response is weak, the infection spreads and, in cases where the victim has an underlying respiratory condition such as asthma or COPD, the cold can develop into a serious illness.
Why the interferon response differs between individuals is not known with any certainty, but it could be due to a number of factors, including genetics. However, it is known that in patients with pre-existing respiratory conditions, the interferon response is inhibited.
That, of course, begs the question for ID creationists: why a system supposedly designed to protect us gets downgraded when it is most needed, and, if the difference is due to underlying genetics, why some people got better genes in this respect than others. Under the ID creationist paradigm, genes that produce any given output are deemed to hold ‘complex specified genetic information’ and, as such, are evidence for intelligent design.
Leaving aside the question of why any omnibenevolent designer would design viruses to make us sick and then design an immune response to prevent them doing so, we are left with the question of why this immune system does not always work very well and why some people have a worse version than others. If an omnibenevolent designer can design an effective immune system, why did it not give it to everyone? Does it actually want those people to suffer more from the viruses it supposedly designed?
The evolutionary explanation is, of course, straightforward, with none of the theological conundrums that plague creationism. Evolution does not seek out perfection and has no interest in equity. In the environment of an evolutionary arms race with viruses, the results are inevitably suboptimal and unevenly distributed throughout the population unless there is particularly strong selection pressure to drive the ‘best’ solution to fixation. It is also in the survival interests of viruses to tone down their victim’s responses, thereby reducing that selection pressure. The resulting trade-off and compromise is what we see today in the different responses to the same virus.
Creationist dogma insists that new genetic information can only be created by their putative intelligent designer, so it should be deeply embarrassing for them to learn that certain stretches of our DNA lengthen as we age, that the rate at which this happens is influenced by genes, and that excessive expansion of these sequences can lead to serious liver or kidney diseases.
This was discovered by researchers from the University of California, Los Angeles (UCLA), the Broad Institute, and Harvard Medical School, who analysed whole-genome sequencing data from 490,416 UK Biobank participants and 414,830 participants in the All of Us Research Program. Their findings were published recently, open access, in Nature.
This research is particularly awkward for creationists because of their insistence on the supposedly ‘sacred’ principle that only their intelligent designer can add new information to a genome. If we concede that claim for the sake of argument, then this newly generated genetic information must have been created deliberately and designed to produce a specific outcome — unless creationism’s designer was simply fiddling about aimlessly. Having a specific outcome (as all genes do) is precisely what William A. Dembski of the Discovery Institute insists is evidence for intelligent design, by a neat process of circular reasoning that only creationists find persuasive.
We then have the additional fact that a high rate of expansion of these DNA sequences is controlled by genetic modifiers and does not occur if any of those genes is not functioning properly. In other words, the resulting liver and kidney diseases are due to what Michael J. Behe famously describes as proof of a designer god: ‘irreducible complexity’.
Still conceding creationist claims, then, Dembski’s and Behe’s own logic demonstrates that their intelligent designer deliberately causes these diseases of old age.
Creationists are further hoist by their own petard in that they traditionally blame disease on ‘The Fall’, thereby conceding that intelligent design creationism is a form of fundamentalist religion rather than science. At the same time, however, they insist that only their intelligent designer can produce the new genetic information responsible for the expansion of these DNA sequences, which neatly rules out the involvement of the vague, non-physical agency they refer to as ‘sin’.
This leaves creationists with an uncomfortable dilemma: either their designer god actively causes liver and kidney disease, or new genetic information can indeed be produced by natural processes in which their designer plays no part — in which case a major plank of creationism collapses. The alternative is to concede that their allegedly omnibenevolent god is directly responsible for serious diseases in elderly people.
It is scarcely worth pointing out the glaringly obvious fact that these outcomes are easily explained as the predictable result of an undirected evolutionary process that has no concept of perfection, inevitably settling for compromise and prioritising reproductive success early in life at the expense of longer-term health and wellbeing.
Recent research has shown that a metabolite of vitamin A, retinoic acid, can quietly inhibit the immune system, making it less responsive to tumours. It also reduces the effectiveness of a promising anti-cancer immunotherapy.
This work, carried out by scientists at the Princeton University branch of the Ludwig Institute for Cancer Research, has resulted in two papers. The first, published in Nature Immunology, describes how retinoic acid produced by the immune system’s dendritic cells (DCs) alters their behaviour, inducing a dangerous tolerance of tumours. The second, published open access in iScience, outlines progress in developing drugs that inhibit retinoic acid production.
To anyone who understands evolution and how it proceeds through a series of sub-optimal “it’ll do” solutions — constrained by what is available at the time and lacking any foresight — it will come as no surprise that the human body’s dependence on vitamin A comes with a downside. These are the inevitable compromises of evolutionary history. What is inexplicable, however, is this vulnerability in terms of intelligent design by an omniscient, omnipotent designer, who should have foreseen such dangers and engineered a better solution — unless, of course, the creation of favourable conditions for cancer was itself part of the design. And that, of course, leads to the theological problems ID creationism leads inexorably to, but ID advocates routinely ignore - a god who is incompetent, indifferent, powerless, or worse still malevolent.
A paper published last November in Nature Communications by an international team lead by scientists from the University of Oslo, is just the sort of evidence against intelligent design and for evolution that creationists normally misrepresent, lie about or ignore, because it illustrates the stark difference between what ID creationism predicts and what we see, and of course, what we see is exactly what the Theory of Evolution predicts. And it's another superb example of how the human body refutes the childish notion of intelligent design by a magic invisible designer, many more of which I have included in my book, The Body of Evidence: How the Human Body Refutes Intelligent Design.
There is a persistent tendency among creationists and Intelligent Design advocates to imagine biology as if it were the product of a competent, benevolent engineer, optimised for lifelong performance and reliability. Real organisms, however, stubbornly refuse to behave like that. Evolution does not design for comfort, longevity, or even cognitive elegance; it shapes traits that maximise reproductive success in the environments in which our ancestors actually lived. Once reproduction has occurred and offspring are independent, the force of natural selection weakens dramatically. From that point on, biological systems are increasingly free to accumulate compromises, trade-offs, and outright failures — not because they are useful, but because there is little evolutionary incentive to eliminate them.
Nowhere is this more obvious than in the ageing human brain. Memory, learning, and cognitive flexibility are exquisitely tuned for early and mid-life, precisely when they matter most for survival, social navigation, and reproduction. Later in life, however, those same systems reveal a striking lack of long-term maintenance. This is not a mystery, nor is it a design flaw crying out for a supernatural explanation. It is exactly what evolutionary theory predicts under mechanisms such as antagonistic pleiotropy, mutation accumulation, and the diversion of finite biological resources away from indefinite repair and towards reproduction. In short, evolution produces brains that are *good enough* for long enough — not brains that are guaranteed to remain intact into old age.
That expectation is strongly reinforced by the paper in Nature Communications, which combines large-scale neuroimaging and cognitive data to examine why memory reliably declines with age even in otherwise healthy adults. Rather than pointing to a single failing component or a neatly isolated genetic “defect”, the study reveals a diffuse pattern of structural brain change, with memory loss emerging from the cumulative erosion of multiple interconnected regions. This kind of widespread, variable vulnerability is exactly what an evolutionary framework anticipates — and exactly the opposite of what Intelligent Design would lead us to expect. What follows is not evidence of poor design, but evidence of no design at all: only the predictable consequences of evolution’s ruthless focus on reproductive success early in life, and its indifference to what happens long after that job is done.
Palaeontologists at the Federal University of São Paulo, Brazil have analysed the DNA recovered from two ancient humans and discovered that they were both carriers of the Human Papillomavirus HPV16, a virus implicated in several cancers. They have presented their evidence, ahead of peer-reviewed publication in the pre-print server, bioRxiv.
The interesting thing from the point of view of virology is that this discovery shed considerable light on when HPV entered the human virome and commenced co-evolving with us, with one theory being that we acquired them from Neanderthals. From the point of view of creationists however, the news could scarcely be worse.
The first sample, obtained from the famous 'Ötzi the Iceman', the 5,300 year-old mummified body recovered from a glacier on the Italian-Austrian border, is probably not too much of a problem for creationists as it just about falls within the timeline of the Bible mythology, apart from the little problem of it being from before they believe the was a general reset of Earth's biosphere in a genocidal flood which would have destroyed the glacier and everything in it, so Ötzi should not have been there.
But, the second is a massive problem, since it was recovered from a leg of a man, Ust'-Ishim man, recovered from western Siberia and dated to 45,000 years BP - way before creationists believe Earth existed, and tens of thousands of years before the mythical 'Fall', when creationists believe viruses didn't exist. This specimen provided the oldest complete human genome so far recovered and the DNA contains the unmistakable genome of HPV16. Creationist mythology just keeps getting further and further from reality as exposed by science using real-world evidence.
Traditionally, creationists claim Earth is 6,000 - 10,000 years old and was created perfect in every way, with no deaths or diseases, so no viruses, parasites or pathogens, bodies that always functioned perfectly and genomes that never failed to replicate perfectly. Then, along came 'sin' which, by some mysterious process, was able to thwart the omnipotent creator god's perfect plan and create viruses and other pathogens and make perfect physiology begin to malfunction and genomes to fail to replicate perfectly, causing variations and genetic weaknesses, etc.
Why a reputedly omnipotent creator failed to anticipate the effects of 'sin' and make its creation robust enough to resist them is never explained, although, apparently, it provided immune systems in preparation for something that, although omniscient, and even claimed to have created 'evil' (Isiah 45:7), it then failed to anticipate. But, as though those myths aren't too ridiculous for any adult with even a basic education to believe, creationists have to continually think of ways to ignore the evidence and continue holding plainly absurd beliefs, under the child-like delusion that their ability to do so is a sign of strength.
The paper itself sets out to address a long-standing question in human virology: how long oncogenic human papillomaviruses have been associated with our species, and whether their origins lie in relatively recent cultural changes or deep evolutionary history.
The Krainer lab developed 12 initial ASO drug candidates. The best performing ASO—ASO-A—completely broke the SRSF1-AURKA-MYC circuit, leading to slower tumor growth and cell death.
Untreated PDAC tumor organoid
PDAC tumor organoid after treatment with ASO-A
CSHL’s Krainer lab has discovered a key oncogenic circuit driving aggressive pancreatic ductal adenocarcinoma (PDAC) progression. Using human PDAC tumor organoids, seen here, the team developed a potential RNA splicing-based therapeutic that collapses the circuit.
These examples of what Discovery Institute fellows Michael J. Behe and William A. Dembski call “irreducible complexity” and “complex specified information” respectively — cited by them as evidence for an intelligent designer — are now being discovered with such monotonous regularity that it is astonishing they never appear in any of the Discovery Institute’s anti-evolution, anti-science propaganda.
The answer to that conundrum is, of course, that such examples are far more frequently found in parasites, pathogens, and idiopathic conditions such as cancer and autoimmune disease. No self-respecting religious fundamentalist is going to open that particular can of worms and appear to be promoting a manifestly malevolent god. It is far safer to remain silent and instead present cult followers with carefully curated examples of supposedly “beneficial” complexity, selected to appeal to their pre-existing biases.
Nevertheless, here is yet another example whose refusal to be addressed by creationists neatly illustrates the disingenuous nature of these alleged “proofs of intelligent design”. The news comes from a paper just published in the Cell Press journal, Molecular Cell, which shows how pancreatic cancer—specifically pancreatic ductal adenocarcinoma (PDAC)—depends on a complex regulatory circuit consisting of three key components.
The research, conducted by a team from Cold Spring Harbor Laboratory (CSHL) and led by former CSHL graduate student Alexander Kral, builds on earlier work by Professor Adrian Krainer, who discovered that the protein SRSF1 jump-starts PDAC. The new study shows that SRSF1 does not act alone, but forms one of three interdependent “pillars” in this malignant system—the other two being Aurora kinase A (AURKA) and the oncogene MYC. In laboratory experiments, disabling any one of these three components using RNA-based therapy collapsed the circuit, reduced tumour viability, and triggered programmed cell death.
In Michael Behe’s terms, reducing the complexity kills the system. In William Dembski’s terms, destroying the “complex specified genetic information” kills the cancer cells.
This leaves creationists who are honest enough to confront the evidence with a stark choice: either this is evidence that their intelligent designer deliberately designed pancreatic cancer, or Behe’s and Dembski’s long-trumpeted “proofs of intelligent design” are nothing of the sort. Some of the less scientifically literate will, predictably, invoke “The Fall”, thereby revealing once again that Intelligent Design creationism is not science at all. It is merely Bible-literalist religious fundamentalism dressed up in a laboratory coat — exactly what the Discovery Institute has been attempting to smuggle into US classrooms ever since the 1987 Supreme Court ruling in Edwards v. Aguillard made it clear that teaching creationism in public schools violates the Establishment Clause of the US First Amendment.
ID advocates should be thrilled to learn that a team of researchers from Technische Universität Dresden (TUD), Germany, together with colleagues from Charles University, Prague, Czechia, have discovered a perfect example of what Discovery Institute fellows William A. Dembski and Michael J. Behe claim is proof of intelligent design—namely complex specified information and irreducible complexity. The team have just published their findings, open access, in Nature Communications.
There is one slight problem, however: this supposed ‘proof of intelligent design’ turns out to be one of the mechanisms that makes cancer so effective at increasing pain and suffering — and at killing people.
This presents creationists with a theological conundrum. Either there is more than one intelligent designer, which comes close to—or even crosses—the line into blasphemy, or the intelligent designer is actively and knowingly creating a cause of pain and suffering, and is therefore not the omnibenevolent deity portrayed in the Bible.
The stark alternative to these theologically insurmountable problems is equally problematic for ID creationism: admitting that their ‘proof of intelligent design’ is nothing of the sort, and is better explained as the result of a natural process in which no intelligence was involved—thereby absolving their god of any culpability.
The TUD-led team discovered that the protein MCL1 not only inhibits programmed cell death, or apoptosis, but also plays a central role in tumour metabolism. Normal, non-cancerous cells will usually self-destruct if their DNA becomes corrupted beyond repair, but when this process fails, a tumour can develop through the proliferation of cells carrying damaged DNA. In cancers, this self-destruct mechanism is suppressed by MCL1.
The team also found that MCL1 is not only responsible for preventing apoptosis, but also dysregulates cellular energy metabolism. In other words, a single factor ensures both cancer cell survival and the functioning of key metabolic and signalling pathways for the benefit of the tumour.
In Michael J. Behe’s terms, all the components of this survival mechanism must be present for the cancer to persist; and in William A. Dembski’s terms, the genetic information coding for MCL1 must constitute highly specified complex information.
Scientists at the Scripps Institute have discovered a defective DNA repair mechanism that would normally trigger cell death but which, paradoxically, keeps cancer cells alive. They have recently published their findings, open access, in Cell Reports. It is exactly the sort of biochemical complexity that creationists routinely mistake for evidence of intelligent design, having been led to believe that well-designed systems must be highly complex. In reality, good intelligent design is minimally complex: complexity increases the risk of failure, is harder to maintain, and is more energetically costly.
The DNA “code” is one of creationism’s favourite props for its familiar ignorance-plus-incredulity-therefore-God-did-it argument — a textbook god-of-the-gaps false dichotomy. Yet even a superficial look beneath the metaphor reveals that DNA replication and repair are very far from the flawless perfection we would expect from an omniscient, omnipotent and omnibenevolent deity — especially when it comes to its supposedly special creation, humankind. What we actually observe is a fragile, error-prone system patched together by evolutionary history rather than foresight.
The system is only needed in the first place because cell replication in multicellular organisms remains essentially identical to that of single-celled organisms. Despite the fact that the benefits of multicellularity arise from cell specialisation into tissues and organs with discrete functions — each requiring only a tiny fraction of the genome — every cell is forced to copy the entire DNA complement every time it divides. This vast waste of energy and resources serves only to multiply the probability of error, and errors are not rare anomalies but routine occurrences. This is not the signature of intelligent design.
The Scripps Institute team have shown that some cancer cells survive precisely because the normal high-fidelity repair system fails. When that happens, a crude backup mechanism takes over — an emergency repair process that is little more than a biological kludge and which introduces further errors as it works. It is rather like calling out an emergency plumber who fixes one leak by installing a long section of pipe riddled with smaller leaks. Would anyone describe that as intelligent workmanship?
Researchers from the University of New South Wales (UNSW), Sydney, Australia, have identified DNA switches that help control how astrocytes work. These are brain cells that support neurons and are known to play a role in Alzheimer’s disease. They have just published their findings in Nature Neuroscience.
Firstly, there is the embarrassment that the cause of Alzheimer’s is indistinguishable from Michael J. Behe’s favourite ‘proof’ of intelligent design — irreducible complexity — in that all the elements must be present for Alzheimer’s to occur.
Secondly, there is the discovery by the Australian team of which triggers ‘switch on’ which genes that affect the astrocytes implicated in Alzheimer’s. These switches are embedded in the 98% of the human genome that is non-coding, or so-called ‘junk’ DNA. Since they can be separated from the genes they regulate by thousands of base pairs, it has been notoriously difficult to identify which switches control which genes. Now, using CRISPR, the team have identified around 150 of these regulatory elements.
The existence of this non-coding DNA has long been an embarrassment for creationists, who have been unable to explain why an intelligent designer would produce so much DNA that does not contain the roughly 20,000 genes that actually code for proteins. Why such prolific waste, adding massively to the risk of errors that can result in cancer?
The creationist response has been to conflate the terms ‘non-coding’ and ‘non-functional’, and then proclaim this ‘functional DNA’ as intelligently designed — reducing, but by no means eliminating, the amount of ‘junk’ they still have to explain away. Of course, ‘non-coding’ does not mean ‘not transcribed’, only that the RNA does not code for a functional protein. However, this non-coding but functional DNA does play a role in gene expression, in that the resulting RNA can act as controls or ‘switches’ that turn genes on and off.
So, creationists — having triumphantly waved ‘functional, non-coding DNA’ as evidence for intelligent design after all — are now presented with the fact that it is part of the ‘irreducible’ cause of Alzheimer’s, and probably the cause of many other diseases with a genetic basis.
In another major embarrassment for those creationists who understand it, researchers at the Gladstone Institutes and Stanford University have developed a method for linking the genome of a cell to diseases caused by specific gene variants. They have recently published their findings, open access, in Nature.
Creationists insist that the human genome was intelligently designed, with every outcome the result of “complex specified information” which, according to Discovery Institute Fellow William A. Dembski, constitutes definitive evidence of intelligent design. If this were true, it would follow that genes which cause disease were intelligently designed to cause those diseases.
The difficulty deepens for creationists when one considers that many diseases involve multiple genes, sometimes hundreds or even thousands, all of which must possess the “correct” variants for the disease to emerge. In other words, some diseases not only depend on Dembski’s “complex specified genetic information”, but also conform to Michael J. Behe’s proposed hallmark of intelligent design: irreducible complexity.
Unless creationists invoke an additional creator—one over whom their reputedly omnipotent and omniscient god has no control—their supposedly intelligent designer must have deliberately created these gene variants to produce the suffering they cause.
By contrast, the evolutionary explanation requires no such mental gymnastics. The existence of genetic variants is exactly what evolutionary theory predicts, and provided such variants remain rare within a population, there is little selective pressure to remove them. A genome produced by an omniscient, perfect designer, however, would contain no such variants: the original design would be flawless, as would the mechanisms responsible for replicating it. The very existence of gene variants is therefore evidence against intelligent design.
The technique developed by the research team is sensitive enough to examine the entire genome and determine which genes influence which cell types. This makes it possible to identify which genes contribute to particular diseases. In cases where a single gene is involved, this can be relatively straightforward, but where many genes are implicated, it can be extremely difficult to disentangle their individual effects—precisely the problem this new technique helps to overcome.
If we take creationist claims about the human body at face value – that we are the special design of an omniscient, omnipotent creator god – we would have to conclude that this putative god equipped us for life in small, dispersed bands of hunter-gatherers, entirely free from the pressures of modern urban existence. That is the inescapable implication of new work by Daniel P. Longman of the School of Sport, Exercise and Health Sciences, Loughborough University, UK, and Colin N. Shaw of the Department of Evolutionary Anthropology, University of Zürich, Switzerland.
In their study, recently published in Biological Reviews, they argue that human evolutionary fitness has deteriorated markedly over the past 300 years, beginning with the Industrial Revolution. They attribute this to the escalating stresses of urban life, which are increasingly linked to counter-survival problems such as declining fertility rates and the rising prevalence of chronic inflammatory conditions, including autoimmune diseases. They also highlight impaired cognitive function in urban settings, with chronic stress playing a central role in many of these conditions.
As they note, our stress responses were shaped in environments where predators such as lions posed intermittent but existential threats. A sudden burst of adrenaline and cortisol – the classic fight-or-flight reaction – made the difference between survival and being eaten. Today, however, we summon exactly the same physiological response to traffic noise, difficult conversations with colleagues or family, and that irritatingly arrogant but ignorant creationist on the Internet. Where a lion encounter would once have been an occasional shock, we now experience the physiological equivalent of facing several lions a day.
For creationists, this poses an awkward problem. An omniscient designer should have foreseen humanity’s future circumstances and endowed us with a physiology robust enough to cope with them. Evolution, by contrast, cannot predict even the next generation, let alone the demands of life tens or hundreds of millennia later. It optimised our ancestors for survival on open African landscapes, not for navigating congested cities, chronic noise, 24-hour information streams, and the relentless stimuli of modern technology. This helps explain why our inherited design is increasingly mismatched to our environment, and why evolution cannot adjust us quickly enough to keep pace.
My own family history illustrates this accelerating mismatch. My grandparents grew up in rural Oxfordshire, before the arrival of the motor car, electricity, modern sanitation, or powered heating. Their lives were essentially unchanged from those of their parents and grandparents. My parents, by contrast, had electricity, piped water, proper sanitation, and radio; later a motor car, a television, and eventually a telephone. Now we have smartphones, laptops, air travel, satnavs, and city centres jammed with traffic. We spend hours each day staring at screens, communicating instantly across the world. My grandparents’ lives would have been recognisable to their great-grandparents, but mine would be unrecognisable to them – such has been the accelerating pace of technological change. No evolutionary process could possibly adapt a species to that speed of environmental transformation.
We are, in effect, experiencing stress levels akin to those of ancestors living among a pride of lions, not merely encountering one on rare occasions. And crucially, we have little or no time to recover before the next ‘lion’ appears.
Researchers at Cedars-Sinai have developed a synthetic RNA molecule that can help repair DNA in damaged tissues such as the myocardium following a myocardial infarction (MI). Their research is the basis for a paper just published in Science Translational Medicine
This raises a troubling question for ID creationists: if scientists can do it, why couldn’t their putative omniscient, omnipotent and, above all, omnibenevolent designer god do it? There are only a limited number of possibilities if we grant the ID proponents their designer god for the sake of argument:
It lacks the ability — in other words, it isn’t omnipotent.
It didn’t know it would be needed — in other words, it isn’t omniscient.
It doesn’t care — in other words, it isn’t omnibenevolent.
It doesn’t want us to repair damaged DNA so we continue to suffer the consequences — in other words, it is malevolent.
This is, of course, just another example of science discovering something that any intelligent, benevolent designer would have anticipated and provided, if such an entity had really designed us.
So, apart from those explanations — none of which flatter their putative designer — the only option left to creationists is that the absence of this DNA repair mechanism is the result of an unintelligent natural process in which their supposed designer played no part, such as evolution.
Unfortunately for them, creationists would have to abandon creationism and admit to being wrong if they accepted the naturalistic explanation. Sadly for them, creationists don’t see admitting being wrong as the intellectually honest thing to do, but as a sign of weakness and giving in to scientists and the physical evidence all ganging up to test their resolve.
This should trouble any creationist who understands the implications, so their cult leaders need to work hard to ensure none of their followers know about these things or develop the intellectual sophistication to appreciate the consequences.
Researchers from Switzerland and Japan, led by Professor Yohei Yamauchi of Eidgenössische Technische Hochschule Zürich (ETH Zürich), have developed a microscopy technique that enables real-time, high-resolution observation of how a virus gains entry to a cell. Their findings are described in the Proceedings of the National Academy of Sciences of the USA (PNAS).
The process, in which a virus exploits the pathways cells normally use to take in larger molecules such as hormones, cholesterol, or iron, involves the active cooperation of the cell as it reaches out to engulf the viral particle. This mechanism is triggered by receptors on the cell surface, to which viruses bind while ‘surfing’ along the membrane, seeking regions rich in receptors to form a stable attachment.
In other words, creationists often portray this as an “irreducibly complex” system, supposedly dependent on all components being present from the outset, requiring what they call “complex specified information” in both virus and cell to produce the receptors and binding proteins. Discovery Institute fellows Michael J. Behe and William A. Dembski present this as evidence of intelligent design.
Their argument depends on a statistical sleight of hand: they treat the entire process as though it originated in a single event involving one cell and one virus, then calculate improbabilities for each step and multiply them together, producing a vanishingly small likelihood of the whole mechanism arising spontaneously. This ignores the fact that evolution operates in populations — often large ones — across long periods, where components accumulate gradually over generations, dramatically increasing the probability of multiple features emerging together in the same lineage.
It also overlooks the billions of years during which viruses and cells have co-evolved. As multicellular organisms evolved ever more sophisticated ways of receiving and responding to external signals and substances, viruses simultaneously improved their ability to exploit those mechanisms.
But to the scientifically illiterate target audience of the ID-creationism industry, evolution is imagined as a single event rather than a continuous process, leaving them oblivious to the misuse of probability and the underlying mathematical errors.
Creationists trying to use this argument for intelligent design usually respond to biologists pointing out the obvious fact that they just presented their putative god as some sort of celestial malevolence, by retreating into Bible literalism and religious fundamentalism and invoking mythical 'Fall', so betraying the claims of the Discovery Institute and its fellows that ID is real science, not bible-literalist creationism dressed in a lab coat, as a lie.
How influenza viruses enter our cellsFor the first time, researchers have observed live and in high resolution how influenza viruses infect living cells. This was possible thanks to a new microscopy technique, which could now help to develop antiviral therapies in a more targeted manner.
In brief
For the first time, a new high-resolution microscopy technique has allowed researchers to watch live as influenza viruses infect cells.
The international team led by ETH Zurich found that the cells actively promote virus uptake.
This technique could now help to develop antiviral therapies in a more targeted manner.
Fever, aching limbs and a runny nose – as winter returns, so too does the flu. The disease is triggered by influenza viruses, which enter our body through droplets and then infect cells.
Researchers from Switzerland and Japan have now investigated this virus in minute detail. Using a microscopy technique that they developed themselves, the scientists can zoom in on the surface of human cells in a Petri dish. For the first time, this has allowed them to observe live and in high resolution how influenza viruses enter a living cell.
Led by Yohei Yamauchi, Professor of Molecular Medicine at ETH Zurich, the researchers were surprised by one thing in particular: the cells are not passive, simply allowing themselves to be invaded by the influenza virus. Rather, they actively attempt to capture it.
“The infection of our body cells is like a dance between virus and cell.
Professor Yohei Yamauchi, corresponding author.
Molecular Medicine Laboratory
Institute of Pharmaceutical Sciences
Department of Chemistry and Applied Biosciences
Eidgenössische Technische Hochschule Zürich
Zürich, Switzerland.
Viruses surf on the cell surface
Of course, our cells gain no advantage from a viral infection or from actively participating in the process. The dynamic interplay takes place because the viruses commandeer an everyday cellular uptake mechanism that is essential for the cells. Specifically, this mechanism serves to channel vital substances, such as hormones, cholesterol or iron, into the cells.
Like these substances, influenza viruses must also attach to molecules on the cell surface. The dynamics are like surfing on the surface of the cell: the virus scans the surface, attaching to a molecule here or there, until it has found an ideal entry point – one where there are many such receptor molecules located close to one another, enabling efficient uptake into the cell.
Once the cell’s receptors detect that a virus has attached itself to the membrane, a depression or pocket forms at the location in question. This depression is shaped and stabilised by a special structural protein known as clathrin. As the pocket grows, it encloses the virus, leading to the formation of a vesicle. The cell transports this vesicle into its interior, where the vesicle coating dissolves and releases the virus.
Previous studies investigating this key process used other microscopy techniques, including electron microscopy. As these techniques entailed the destruction of the cells, they could only ever provide a snapshot. Another technique that is used – known as fluorescence microscopy – only allows low spatial resolution.
Combined techniques, including for other viruses
The new technique, which combines atomic force microscopy (AFM) and fluorescence microscopy, is known as virus-view dual confocal and AFM (ViViD-AFM). Thanks to this method, it is now possible to follow the detailed dynamics of the virus’s entry into the cell.
Video: Nicole Davidson / ETH Zurich.
Accordingly, the researchers have been able to show that the cell actively promotes virus uptake on various levels. In this way, the cell actively recruits the functionally important clathrin proteins to the point where the virus is located. The cell surface also actively captures the virus by bulging up at the point in question. These wavelike membrane movements become stronger if the virus moves away from the cell surface again.
The new technique therefore provides key insights when it comes to the development of antiviral drugs. For example, it is suitable for testing the efficacy of potential drugs in a cell culture in real time. The study authors emphasise that the technique could also be used to investigate the behaviour of other viruses or even vaccines.
Significance
Influenza A viruses (IAVs) continue to cause epidemics worldwide due to their high mutability. Nevertheless, the initial step of infection, viral uptake into cells, has been challenging to observe directly with conventional microscopy techniques. Here, we developed a hybrid imaging system combining atomic force microscopy and confocal microscopy with enhanced mechanical functionality and minimal invasiveness to directly visualize nanoscale dynamics of IAV and cell membranes during viral uptake into living cells. This system enables the analysis of IAV lateral diffusion resulting from IAV–membrane interactions and characteristic membrane morphological changes induced by IAV during endocytosis. Our approach offers a method to rapidly assess the impact of viral mutations on host cell entry, which is critical for understanding emerging IAV variants.
Abstract
Influenza A virus (IAV) entry into host cells begins with interactions between the viral envelope proteins hemagglutinin (HA)/neuraminidase (NA) and sialic acid moieties on the cell plasma membrane. These interactions drive IAV’s lateral diffusion along the cell membrane and trigger membrane morphological changes required for endocytosis. However, directly visualizing these dynamic processes, which are crucial for IAV entry, has been challenging using conventional microscopy techniques. In this study, we enabled live-cell observation of nanoscale morphological dynamics of IAV and the cell membrane by reducing the mechanical invasiveness of atomic force microscopy (AFM). A customised cantilever with less than half the spring constant of conventional cantilevers enabled virus-view AFM imaging that preserved IAV–membrane interactions. By combining virus-view AFM with confocal microscopy, we performed correlative morphological and fluorescence observations of IAV lateral diffusion and endocytosis in living cells. Variations in diffusion coefficients of single virions suggested heterogeneity in sialic acid density on the cell membrane. NA inhibition decreased diffusion coefficients, while reduced sialic acid density increased them. The timing of clathrin accumulation at virion binding sites coincided with a decrease in diffusion coefficients, a relationship that was maintained independent of NA activity or sialic acid density. As clathrin assembly progressed, ~100-nm-high membrane bulges emerged adjacent to the virus, culminating in the complete membrane envelopment of the virus at peak clathrin accumulation. Our virus-view AFM will deepen our understanding of various virus–cell interactions, facilitate the evaluation of drug effects and promote future translational research.
Influenza A virus (IAV) is an enveloped RNA virus with two key surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA). The virus surface contains 300 to 400 HA and 40 to 50 NA molecules (1). IAV envelope proteins comprise at least 18 HA and 11 NA subtypes (2), which enable IAV to infect various host species including humans, birds, pigs, bats, and other animals (3). These envelope proteins play crucial roles in IAV infection of host cells.
They interact with sialic acids on cell surface glycolipids and glycoproteins (4) or with major histocompatibility complex class II (MHC class II) molecules (5–7). HA binds to sialic acids at the terminal ends of glycan chains on the cell surface. The HA–sialic acid interactions are inherently weak, with dissociation constants typically in the millimolar range (0.9 to 68.4 × 10−3 M) (8–10). However, multivalent binding of multiple HAs to sialic acids enables IAV to stably adhere to the cell membrane (11, 12). Meanwhile, NA catalyzes the cleavage of sialic acids (13), inhibiting stable adhesion of IAV to the cell membrane. Through these mechanisms, HA and NA effectively regulate the attachment and detachment of IAV to the cell membrane.
The competitive action between HA and NA allows IAV to diffuse laterally along the cell membrane surface topology (). This lateral diffusion represents a critical dynamic macroscopic phenomenon reflecting virus–membrane interactions. However, conventional microscopy techniques have struggled to detect IAV movement on the 10-nm-thick cell membrane, resulting in limited visualization success (15–18).
HA-NA-sialic acid interactions also trigger endocytosis involving morphological changes of the cell membrane. When diffusing IAV binds to functional receptors such as EGFR (19) and Cav1.2 (20) through sialic acids, it initiates the recruitment and assembly of the endocytic machinery including clathrin, actin, and dynamin. IAV utilizes multiple entry pathways including clathrin-mediated endocytosis (CME), macropinocytosis, and both clathrin-independent and dynamin-independent mechanisms (16, 21–23).
IAV primarily utilizes CME for cellular entry (16, 21). Previous imaging of membrane dynamics using atomic force microscopy (AFM) has revealed that in IAV-free CME, clathrin-coated membrane invaginations (pits) larger than 100 nm in diameter form (24, 25). This is accompanied by the emergence of actin-dependent membrane bulges that develop on one side of the pit and eventually lead to its closure. Although electron microscopy has provided morphological snapshots of pits during IAV internalization (26), the membrane dynamics during IAV internalization via CME have yet to be successfully visualized.
AFM enables mechanical imaging of sample morphology with nanometer-scale resolution (27, 28). Since the development of high-speed AFM in 2001 (29), this technique has contributed significantly to molecular dynamics analysis (30–36). Additionally, the advent of cell-imaging AFM in 2013 has enabled advances in membrane dynamics analysis (37, 38). The integration of cell-imaging AFM combined with confocal microscopy has provided unique capabilities for observing nanoscale membrane morphological changes in living cells (24, 25). Despite these advances, a major challenge persists: the mechanical interference of the cantilever with biological samples. Visualizing the dynamic processes of IAV lateral diffusion and internalization requires an innovative technology capable of simultaneously observing the nanoscale morphology of the 10-nm-thick cell membrane and the 100-nm spherical IAV interacting with cell surface sialic acid-bearing glycolipids and proteins. Given that multivalent IAV–membrane interaction forces are relatively weak, ranging from 10 to 25 pN (39), achieving low-invasive imaging capabilities is critical.
In this study, we address and overcome the challenge of mechanical interference by enhancing the low invasiveness of AFM through the use of a customised soft cantilever. In combination with confocal microscopy, low-invasive AFM enables simultaneous live-cell imaging of both morphology and fluorescence. The redesigned cantilever minimizes disruption of IAV–membrane interactions, allowing accurate observation of viral dynamics. Using this system, we investigated the lateral diffusion of single IAV particles under various conditions, including NA inhibition, reduced cell surface sialic acid density, and different viral subtypes. We also analyzed membrane morphological changes before and during IAV endocytosis. While fluorescently labeled IAV was primarily used, we also demonstrate our AFM’s capability to track unlabeled viruses. This virus-view dual confocal and AFM, called ViViD-AFM, enables correlative morphological and fluorescence imaging of IAV–membrane dynamics, providing nanoscopic insights into HA-NA-sialic acid interactions.
What ID advocates never seem to notice is that, in arguing that such mechanisms must have been deliberately engineered, they are attributing to their designer a system in which viruses are given exquisitely tailored tools for invading the very cells it supposedly created. If one insists that this is intentional design, then one must also accept that the designer crafted the molecular equivalent of lockpicks and battering rams, optimised for breaching living tissue. It is difficult to reconcile this with any notion of benevolence.
Indeed, by rejecting evolution as the explanation for viral entry, ID proponents corner themselves into an uncomfortable theological stance: their designer not only equipped viruses with the machinery to exploit cellular signalling, but also ensured that cells remained vulnerable to such exploitation. The result is an ecosystem in which suffering, disease, and death are not unfortunate consequences of natural processes but deliberate design choices.
This is, of course, why mainstream biology requires no such designer. Co-evolution naturally explains why cells have receptors essential for communication and nutrient uptake, while viruses have, over immense timescales, adapted to hijack those same pathways. No malevolent architect is required—only the simple, iterative logic of variation, selection, and replication.
Yet the ID movement persistently overlooks this simpler, evidence-based account, preferring instead an argument that—if taken seriously—presents their putative creator as either unable to prevent viral parasitism or fully complicit in engineering it. Neither option supports the benevolent, omnipotent designer they hope to defend.
