No, There Did Not Occur Cognitive Rejuvenation Through Reprogramming of Cells

 A recent article in MIT Technology Review is entitled "Why 'reprogramming' is the buzziest approach to reversing aging right now." It starts out by correctly discussing previous dead ends in rejuvenation research, attempts to slow or reverse aging. Then the article goes into hype mode, trying to promote something called "cellular reprogramming." The article claims this:

"Some promising studies in mice suggest that this approach might help wind back the clock. It seems to improve tissue healing, restore vision, and even improve learning and memory."

We are told that billions are being invested into startups trying to do this "cellular reprogramming," and a mention is made of three startups that are not publicly traded (Altos Labs, Retro Biosciences and NewLimit) We are told that billionaires are pouring lots of money into these startups. 

The link above for the phrase "improve learning and memory" takes you to the paper "Cognitive rejuvenation through partial reprogramming of engram cells."  Let me explain why that paper is a low-quality paper that fails to provide any decent evidence for any such thing as "cognitive rejuvenation." The paper claims to have improved memory in mice, but does not publish any robust evidence to support such a claim. 

The first reason the paper is not a high-quality study is its failure to use large enough study group sizes. You should not get the wrong idea when the paper refers to using 39 mice. Those mice were divided into various different study groups, leaving too-small study group sizes such as a study group size of only 7 mice and a study group size of only 15 mice, a study group size of only 11 mice, a study group size of only 12 mice, and a study group size of only 5 mice. No paper like this should be taken seriously unless all of its study groups were at least 15 to 20 animals per study group. Almost always the study group sizes needed for reliable results in neuroscience experiments of this type are sizes of 20 animals or greater. 

The second reason the paper is a low-quality study is that it used poor methods to test memory in the mice it used. The first type of method used was the utterly unreliable method of trying to judge "freezing behavior" in mice. My post here explains at great length why this method is utterly unreliable as a technique for testing memory performance. That post is entitled "All Papers Relying on Rodent 'Freezing Behavior' Estimations Are Junk Science."

When "freezing behavior" estimations go on, things typically work like this. A rodent will be trained to fear some thing such as a shock plate that gives the rodent a shock when the rodent steps on it. Then later the rodent will be placed in a cage that includes the fear stimulus such as the shock plate. The researchers will attempt to record what percentage of some time (say, a minute or 3 minutes) that the rodent was immobile when placed in such a case. This will be called a "freezing percentage," and will be claimed as a measure of how well the rodent remembered the fear stimulus. 

The technique makes no sense. In the real world, rodents don't usually freeze and become immobile when they are afraid. They are much more likely to flee. So trying to judge recall of a fearful stimulus by judging how much time a rodent was immobile in a cage makes no sense as a measuring method. The thing that utterly destroys the credibility of all "freezing behavior" graphs is that they can be produced in any of more than a dozen ways. A researcher can put a rodent in the cage for three minutes and graph the whole three minutes. Or he can graph only the first 30 seconds, or only the first minute, or only the first two minutes. In each ten seconds of such a three minutes, the researcher can count it as "moving" if the rodent moves one second during that period; or the researcher can count two seconds of movement as being mobility; or the researcher can use three seconds, or four seconds, or five seconds. 

There are no prevailing standards for how "freezing behavior" is judged. With there being a dozen different possibilities of how "freezing behavior" can be judged and graphed, with each having a possibility of success of about 50%, it will be almost certain that the researcher will be able to choose some analysis method that will show the desired difference in "freezing behavior," even if the memory intervention being tested had no real effect. This is a large part of the reason why "freezing behavior" judgments are worthless as evidence for an increase or decrease in memory in rodents. Such "freezing behavior" judgments are very common in neuroscience research, but that is just another indication of the very sick state of today's neuroscience research, where there prevails a wide variety of pathologies. 

Here is the "freezing behavior" graph from Figure 1 of the paper "Cognitive rejuvenation through partial reprogramming of engram cells." Its appearance matches closely the general appearance of a junk science "freezing behavior" graph as I outlined it in the diagram above that I made months before reading this paper.

We have three indications here of utterly unconvincing results and junk science:

(1) A use is made of the "freezing behavior" method which is an utterly unreliable method, for the reasons discussed above. 

(2) Failing to follow principles of good science, the authors have failed to even list in their graph what span of time was used to judge this alleged "freezing behavior."

(3) The study group sizes used were too small for any reliable result to be claimed. You can tell the study group sizes here by counting up the number of circles in front of each of the bars in the graph above. Each circle represents one mouse. The graph showed that the study group sizes were only 12 mice for one study group, and only 9 mice for another study group. A convincing study would have required at least 15 or 20 mice per study group. 

The authors of the paper also used another technique to try to measure memory performance. That technique was the widely used Morris water maze test (MWM). The Morris Water Maze test can be a fairly reliable way of measuring recall in rats, if the test is used in a straightforward way. The water maze consists of a circular open tank rather like a child's bathing tub, deeper than a rodent's length, with a hidden platform on one side of the tank, about an inch or two below the water surface. The tank is filled with a milk-colored white fluid, typically by pouring something in water to make it opaque.. A rodent is placed in the tub, and has to tread water to stay alive. Eventually the rodent will discover that by swimming to the hidden platform the rodent can comfortably rest, without having to tread water.  You test the rodent's memory by exposing him to the water maze a certain number of times, until you find that the rodent immediately goes to the hidden platform.  Then later the rodent's memory can be tested by putting the rodent in the same Morris Water Maze tank, and seeing whether it quickly swims to the platform. 

The Morris Water Maze test (MWM) may be a fairly reliable technique for testing memory, when it is used with rats, in a straightforward way, with an adequate study group size. By "in a straightforward way," I mean doing something such as simply recording the time it took rats placed in the Morris Water Maze to reach the submerged platform. This time is called the "escape latency" time.  When the Morris Water Maze test is done in a reliable way, we will see a simple bar graph comparing this "escape latency" time for two different groups, an experimental group and a control group. That "escape latency" is simply the average time it took a rat in the group to reach the submerged platform. The graph might look like the graph below. If the study group size was large enough, this might be good evidence that the experimental group was remembering better than the control group. 

But there are many studies that use the Morris Water Maze test (MWM) in an objectionable way, doing analytics in a way that is not straightforward, in a way that smells like "keep torturing the data until it confesses." For example, we may see charts showing how much time rats spent in a particular quadrant of the Morris water maze. Or we may see charts plotting the exact path that particular rats traversed in the Morris Water Maze test.  When data analysis this complicated and arbitrary starts going on, there then occurs a plummeting of the reliability the Morris Water Maze (MWM) as a test of memory. Whenever you are allowed to analyze data in very many different ways, you will be able to find some desired difference between a control group and an experimental group. Finding that difference will be as easy as getting a desired "heads" flip of a coin when you are free to flip the coin a dozen times. 

It is just that type of shortcoming that occurs in the paper "Cognitive rejuvenation through partial reprogramming of engram cells." We have some data showing results of experiments using the Morris Water Maze test (MWM). But the results do not include a single diagram like the one shown above. Instead we have convoluted analysis that smells like "keep torturing until it confesses." We fail to get any convincing simple and straightforward graph seeming to show superior memory in the rodents that supposedly underwent "cellular reprogramming." The study group sizes used in the Morris Water Maze test part of the paper are all lower than the minimum of 15 to 20 animals per study group that are required for decent statistical evidence. 

There's another reason why the results of the Morris Water Maze test (MWM) in the paper "Cognitive rejuvenation through partial reprogramming of engram cells" are not convincing: the fact that in that paper the test was done with mice rather than rats. The Morris Water Maze test is not a reliable way to test memory when it is done with mice. 

Referring to the scientific paper here, the Wikipedia.org article on the Morris water maze test (MWM) now states the following:

"Changes in measures of Morris water navigation task performance may not necessarily reflect specific impairments in mechanisms of spatial learning or memory. The reason for a longer time spent looking for the platform, or the lack of searching in the target quadrant, may not necessarily have to do with an effect on the rat's or mouse's spatial memory, but can be due to other factors. For example, a large study of Morris water navigation task performance in mice concluded that almost half of all variance in performance scores was due to differences in thigmotaxis, the tendency of mice to stay close to the walls of the pool. About 20% of the variability was explained by differing tendencies of mice to float passively in the water until 'rescued' by the experimenter. Differences in spatial memory were only the third factor, explaining just 13% of the variation between animals' performance.[16]"

The result above is one that clearly tells us that the Morris Water Maze test (MWM) is simply not a reliable test of memory when it is performed on mice. It's a different story with rats, because with rats the test is more reliable. 

So the truth is that the paper "Cognitive rejuvenation through partial reprogramming of engram cells" fails to provide any convincing evidence that its claimed "partial reprogramming" did any such thing as a memory improvement or a "cognitive rejuvenation" on the mice that were manipulated. The paper also fails to provide any decent evidence of any such thing as "engram cells" in the sense of cells storing memories. A groundless use of the phrase "engram cells" is epidemic in today's cognitive neuroscience. Neuroscientists are groundlessly applying that term to groups of cells, without doing anything to adequately justify the use of that term. 

We now have a very ironic situation in which billionaires overflowing with cash are sometimes investing many millions or billions in a way that will probably be pretty much flushing money down the toilet. Such investments are based on "brains make minds" and "brains store memories" ideas that are incorrect. Such investments are being made by those eager to never have an earthly death. But when you adequately understand the many reasons why brains cannot possibly be the source of the human mind and cannot possibly be the storage place of human memories, and why each of us must be mentally something vastly more than any brain effects (reasons discussed in great detail in the posts of this blog and in 280+ posts and very many other posts of another blog of mine), you will tend to lose your fear of having an earthly death. Those very reasons are reasons telling us strongly that we are souls that will survive earthly death. 

"Microelectrode Rape": Experimenters Penetrating Sickest Epilepsy Patients Too Dazed to Provide Real Informed Consent

There is a very serious scandal that has been long covered on this blog, a scandal that the mainstream press has ignored. This is the scandal of very sick epilepsy patients being recklessly endangered by experiment-performing brain experts implanting medically unnecessary microelectrodes deep into the brains of such patients.

Epilepsy patients suffer from seizures, which have been described as electrical storms in the brain. When people have epilepsy, the first line of treatment is drugs such as levetiracetam. Such drugs work to prevent seizures for the great majority of epilepsy patients. But for a  small fraction of epilepsy patients, such drugs do not work. Such patients are called drug-resistant epilepsy patients.

The sickest type of epilepsy patient is one suffering from frequent seizures that cannot be controlled by drugs, seizures so bad and so frequent that brain surgery is needed, to stop seizures that may be occurring in the patient as often as 15 times a day. Such surgery typically involves extracting a portion of the brain, for the sake of preventing the seizures. It's a drastic approach, but it can be surprisingly effective. And the cognitive effects are typically relatively minor -- just as we would expect if the brain is not the source of your mind, and not the storage place of your memories. Amazingly, there has often occurred the removal of an entire half of the brain in operations to prevent epileptic seizures.  My post here discusses how such operations have often involved little damage to either memory or mental capacity, contrary to the dogma that brains store memories and that brains produce thinking. 

Usually the surgical operation to try to prevent seizures involves some excision of brain tissue less than the removal of a full half of a brain. To try to help determine where to extract brain tissue without causing cognitive damage or functional damage, medical professionals will typically use electrodes to try to determine which brain areas seizures are coming from. So the skull of a sick epilepsy patient may be opened up, and electrodes may be placed on particular spots of the brain.

At this point there may enter an experimental neuroscientist.  The experimental neuroscientist may say something like this to a doctor: 

"So, you're already opening up this guy's skull to implant electrodes on his brain. How about implanting some additional electrodes -- some more deeply implanted microelectrodes that will monitor the firing of individual neurons? I would like to do a particular type of experiment that requires data on the firing of individual neurons, and this is a great opportunity for such an experiment." 

At this point a good doctor properly guarding the best interests of his patients should always give the same answer, saying something like this:

 "Get the f*** out of here, you parasite! The last thing in the world my horribly suffering patient needs is to be involved in is some damn experiment that may endanger him unnecessarily! I am trying to HEAL this sick-as-hell person, goddammit!"

But very sadly, many doctors are failing to act in such a way. Instead many doctors are giving a green light to neuroscientists wanting to use very sick epilepsy patients for neuroscience experiments involving microelectrode implantation. The goal of the neuroscientist may be to monitor the exact firing rate of individual neurons. Such a thing has no use in evaluating what parts of the brain should be removed to stop seizures. And no reliable science results, because what goes on is typically pareidolia "noise mining" correlation fishing using study group sizes way too small to provide robust evidence of anything. 

While the implanting of regular electrodes may be necessary for surgical evaluation of epilepsy patients, the implanting of microelectrodes is not necessary for surgical evaluation. A scientific paper tells us, "Sixty-five years after single units were first recorded in the human brain, there remain no established clinical indications [i.e. medical justifications] for microelectrode recordings in the presurgical evaluation of patients with epilepsy (Cash and Hochberg, 2015)."

Implanting microelectrodes in the brain of very sick epilepsy patients about to undergo surgery is a sickening case of the abuse of the weakest for the sake of the powerful, the powerful being the scientists conducting such experiments. The medically unnecessary implantation of microelectrodes has very serious risks. 

A paper tells us this:

"A recent meta-analysis reviewed complication rates and types of complications in patients undergoing subdural grid implantation for seizure mapping [41]. The most common complication which was reported was intracranial haemorrhage with a mean rate of 4% closely followed by other complications such as neurologic infections, superficial infections and elevated intracranial pressure. They also found that an increased number of electrodes (>67 electrodes) was independently associated with complications."

Another paper tells us this:

"There are definite medical risks associated with the use of intracranial electrodes. The complication rate of subdural electrodes has been reported to range between 6% and 26%.19–23) Relatively common adverse events associated with subdural electrodes are fever, headache, and nausea.24) Another group reported transient cerebrospinal fluid (CSF) leakage (13–31%), infection (6–8%), intracranial bleeding (8%), and cerebral edema in addition to an intracranial mass effect.25) Nair et al. reported that complications included (in the order of their frequency) infection, transient neurological deficit, epidural hematoma, increased intracranial pressure, and infarction.2) An increase in the complication rate was associated with (a) a greater number of grids/electrodes, (b) longer duration of monitoring, (c) older age of the patient, (d) left-sided grid insertion, (e) the use of burr holes in addition to craniotomy, and (f) an earlier year of monitoring (most likely a reflection of the aforementioned surgeon’s experience)."

But, you may say, the scientists doing these experiments say that they got "informed consent" from the epilepsy patients who they penetrated with microelectrodes. But did they really do that? There is the serious question of whether it is really possible to get any meaningful or adequate degree of "informed consent" from some patient suffering from very bad or very frequent seizures, seizures so bad that doctors are about to cut out a sizable part of the person's brain. 

What do you call it when someone penetrates another person, a person who is not mentally fit to be providing full meaningful consent? Typically such actions fall under categories called second-degree rape or third-degree rape. 

When people think of rape, they think of first-degree rape, when someone rapes another person who is actively resisting or screaming her non-consent. But under the law there are other categories of rape, what are called second-degree rape or third-degree rape. In some of the 50 states of the United States, a person is guilty of third-degree rape if he commits sexual penetration into someone lacking the mental capacity to give consent.  That lack of mental capacity may be for various reasons including intoxication or other factors that may affect normal mental functioning. In Louisiana, for example, you can be found guilty of third-degree rape if you had sex with a person who was intoxicated. 

But, we may ask, is there any big difference between the mental incapacitation of someone intoxicated and someone suffering up to 15 seizures a day? Are not both of these in the same class of mental incapacitation?

What is it called in Louisiana if you unnecessarily penetrate the vagina of some woman who is drunk? That is called third-degree rape. But what should we call it when a neuroscientist unnecessarily penetrates with microelectrodes the brain of some epilepsy patient suffering many seizures a day, some patient too dazed and debilitated and confused to be giving any "informed consent" worthy of the name? Perhaps that should be called "microelectrode rape."

In the conversation below, an authority is setting up a rape.

Authority: So you have those horrible seizures 15 times a day -- I want to help. So can I open up your brain to evaluate you for surgery?

Groaning, dazed epilepsy patient: Sure, Doc, whatever you want, just stop these damn seizures that are driving me crazy!

Authority: And my colleague wants to insert his penis into your vagina. 

Groaning, dazed epilepsy patient: Sure, Doc, whatever you want, just stop these damn seizures that are knocking me out 15 times a day! 

No very meaningful degree of "informed consent" is going on here, so there would probably be a crime of third-degree rape if this proceeds. And what goes on in the conversation below seems just as bad. 

Authority: So you have those horrible seizures 15 times a day -- I want to help. So can I open up your brain to evaluate you for surgery, and hook up some electrodes?

Groaning, dazed epilepsy patient: Sure, Doc, whatever you want, just stop these damn seizures that are driving me crazy!

Authority: And I also want to insert into your brain another type of electrode called microelectrodes, for the sake of an experiment I want to perform.   

Groaning, dazed epilepsy patient: Sure, Doc, whatever you want, just stop these damn seizures that are knocking me out 15 times a day! 

No very meaningful degree of "informed consent" is going on here, and the authority doing such penetration is probably guilty of a crime of abuse and endangerment, something as bad as third-degree rape. We might reasonably use the term "microelectrode rape" to describe such crimes of abuse and endangerment, which take place against people so sick and so dazed and mentally disabled that they probably are not giving any meaningful or sufficient degree of informed consent. 

The fact that the authorities doing such sinister penetrations get a signed document from those they abuse and endanger means very little. Is there any meaning when you get a "hurry up and sign" signature under conditions such as these? 

Almost always the brain experts we might suspect of being guilty of these "microelectrode rapes" (similar to third-degree rapes) fail to publish any informed consent document signed by the subjects horribly endangered by these experiments. Such studies almost always fail to give us specific information on the small number of patients that had microelectrodes implanted.  So we are left unable to judge just how dazed, confused, disabled and mentally damaged the victimized experimental subjects were. We never seem to get something such as MMSE test results allowing us to know how mentally competent the experimental subjects were, or links to videos demonstrating that the patients were mentally fit to be giving a sufficient amount of informed consent. We also never get follow-up information informing us about whether or not there were medical complications arising from such unnecessary implantation of microelectrodes. When analyzing these microelectrode implant experiments, our rule of thumb should be: whenever a paper fails to document mental competency in its experimental subjects, and fails to document them signing completely candid documents that people in their state would be able to understand, then we should assume a lack of any real informed consent, with the result being something we might rightfully call  "microelectrode rape" resembling third-degree rape.

I was able to find an example of an informed consent form for one of these microelectrode implant experimental studies. One was a 4-page form looking about as long as the form in my visual above. The form was so badly filled with jargon and confusing text that there would seem to be little chance that it would be adequately understood by anyone suffering from many seizures every day. This informed consent document falsely described the risks involved, claiming that microelectrodes do not involve risks beyond those posed by regular electrodes implanted in the brain. The reality is that the risk is proportional to the number of electrodes implanted, and that implanting microelectrodes (in addition to regular electrodes) always does involve very much additional risk to the patient, risk that does him no good. 

This so-called "informed consent" document I found for microelectrode experimentation fails to even state the most basic fact of what will occur, which is experimenters inserting tiny wires deep into someone's brain.  It is deceptive to claim that a document of this type is getting "informed consent" for microelectrode experimentation in which such penetrations occur in the brains of epilepsy patients. We can only wonder: how many other so-called "informed consent" documents for microelectrode experiments have the same huge defect?  

Informed consent documents for experiments like this routinely have a "Possible Benefits" section. Typically such sections confess that no benefit is coming to the patient participating. The same section will routinely have some claim such as the claim that "Society will benefit from the scientific knowledge obtained." Experiments involving microelectrode implants in epilepsy patients almost always are very low-quality junk science studies involving very bad Questionable Research Practices such as the use of way-too-small study group sizes much lower than 15. Failing to provide robust evidence of anything important, such studies do not actually benefit society, and often harm society to a tiny degree, when their authors write misleading boastful claims about their activities plagued by noise-mining, dubious correlation-fishing and pareidolia. Almost always, the only people really benefiting from such studies are scientists who get an additional paper to add to their count of published papers, and who get the desired research grant money from some government which should not be funding morally objectionable studies of this type.  

When neuroscience experiments are being done on humans, the very idea of following a mere "informed consent" is a profoundly defective one. A more stringent standard would have to be followed in order for good morality to be practiced in neuroscience experiments on humans. You might call such a standard the standard of "risk-cognizant consent."

The idea of risk-cognizant consent would be to verify that a subject understood all of the risks involved in an experiment, not merely that he had been informed of such risks in a way that might well have failed to cause a good understanding of the risks. Here is how such a protocol of risk-cognizant consent might work. 

(1)  Consent documents would be crystal-clear documents carefully written according to a "plain English" standard.

(2) All risks would be candidly discussed, including known risks, and unknown risks that it might be reasonable to suspect the subject was incurring. 

(3) Before any subject was asked to sign such a document, his or her reading skills would be verified (for example, he might be asked to read the first paragraph aloud). 

(4) Anyone lacking very good reading skills would be offered the consent document in an audio form or video form, or would have the consent document read to him.

(5) It would be made clear that a test would be given on the content of the consent document, and that therefore it should be studied very carefully. 

(6) It would always be verified that the person had spent adequate time studying the written consent document or listening to the audio form of the document, without any of the nonsense going on in emergency rooms, where people are routinely given long documents and pressured to quickly sign them, with medical personnel routinely accepting signatures when people obviously had not taken adequate time to sign what they had read. 

(7) All persons signing such a document would then be given a ten-question multiple-choice test trying to determine how well they understood the information in the consent document. 

(8) Any persons failing to score very highly on such a test (such as scoring 9 out of 10 or higher) would be excluded from participation in the experimental study.

It is not practical to follow this type of protocol in a rushed hurry-up environment such as a hospital emergency room in which someone's life may depend on speedy action  But neuroscience experiments never have so tight a time factor. With neuroscience experiments, there is abundant available time to follow a morally responsible protocol such as the risk-cognizant standard I have described. A mere "informed consent" protocol is not an adequate standard for neuroscience experiments. 

I advise anyone involved in any type of neuroscience experiments to save a copy of any consent document signed,  to gather the names of any persons involved in the experiment, and to carefully document any health problems that may conceivably have been caused by participation in the experiment. Such data may be useful if the person wants to later file a lawsuit seeking damages. 

AI Slop Worsens the Degenerative Spiral of Biology Research

 My long 2021 post "'The Degenerative Spiral of 'Grand Explanation' Academia" was one that painted a troubling portrait of malfunction and deceit in the world of academic researchers purporting to have grand explanations for great mysteries of nature. Has there been improvement since that time? To the contrary, things seems to be getting worse. As Exhibit A to back up the claim that the generative spiral of "grand explanation" academia is worsening, I may offer a recent article by Ross Andersen in The Atlantic, one entitled, "Science Is Drowning in AI Slop." We read this, referring to the "large-language models" used by so-called artificial intelligence or AI:

"Almost immediately after large language models went mainstream, manuscripts started pouring into [scientific] journal inboxes in unprecedented numbers. Some portion of this effect can be chalked up to AI’s ability to juice productivity, especially among non-English-speaking scientists who need help presenting their research. But ChatGPT and its ilk are also being used to give fraudulent or shoddy work a new veneer of plausibility, according to Mandy Hill, the managing director of academic publishing at Cambridge University Press & Assessment. That makes the task of sorting wheat from chaff much more time-consuming for editors and referees, and also more technically difficult."

We read about companies called paper mills that help scientists produce papers, either by generating from scratch a fake paper, or by generating dubious or fake paragraphs or dubious or fake images that a scientist can use in his paper. AI makes it much easier for such science fakery to occur. These paper mill companies don't have advertisements with phrases such as "We'll Help You Fake Things!" Instead, they claim to offer "editorial services" or maybe "creative consulting" or "literary facilitation" or some other euphemism.

It seems that many scientists use such "paper mills" to speed up the job of producing a scientific paper, in a shady way similar to a football player taking banned steroids to boost his performance. But with all the AI tools out there, such as ChatGPT, it seems that a scientist does not even have to become involved with external paper mills. Similar results can be achieved from a scientist's desktop, when he uses some AI tool such as ChatGPT. 

We read that AI tools are also being used to write peer reviews. The article says, "Pangram Labs recently analyzed thousands of peer reviews that were submitted to ICLR, and found that more than half of them were written with help from an LLM, and about a fifth of them were wholly AI-generated."  We read this: "AI science slop has spread beyond the journals now, and is also overrunning other venues for disseminating research."

Preprint servers are sites such as the Cornell physics paper server and the biology preprint server Biorxiv.  Andersen states this:

"But in the months after ChatGPT was released, preprint servers experienced the same spike in submissions that journals did. Ginsparg, who is now a professor of information science at Cornell, told me he hoped that this would be a short-lived trend, but the rate of submissions continues to rise. .. A similar influx of AI-assisted submissions has hit bioRxiv and medRxiv, the preprint servers for biology and medicine. Richard Sever, the chief science and strategy officer at the nonprofit organization that runs them, told me that in 2024 and 2025, he saw examples of researchers who had never once submitted a paper sending in 50 in a year."

Andersen ends on this gloomy note, describing the most severe degenerative spiral of the scientific literature:

"When I called A. J. Boston, a professor at Murray State University who has written about this issue, he asked me if I’d heard of the dead-internet conspiracy theory. Its adherents believe that on social media and in other online spaces, only a few real people create posts, comments, and images. The rest are generated and amplified by competing networks of bots. Boston said that in the worst-case scenario, the scientific literature might come to look something like that. AIs would write most papers, and review most of them, too. This empty back-and-forth would be used to train newer AI models. Fraudulent images and phantom citations would embed themselves deeper and deeper in our systems of knowledge. They’d become a permanent epistemological pollution that could never be filtered out." 

Synapse Strengthening is Way, Way Too Slow to Explain Instant Learning

The Kavli Foundation is a foundation founded by millions of dollars in grants from the late Fred Kavli. The foundation issues science prizes and science grants. One of its semi-annual prizes is in neuroscience. An earlier post on this blog described the bunk and misleading information that occurred when the 1 million dollar Kavli Prize in neuroscience was announced in 2024.  Recently the Kavli Prize was awarded to neuroscientists involved in work on protein synthesis in dendrites: Oswald Steward, Christine Holt, Kelsey Martin and Erin Schuman. The announcement of the prize award makes no mention of learning or memory, merely stating this: "THE KAVLI PRIZE IN NEUROSCIENCE IS AWARDED TO: Christine Holt, Kelsey Martin, Erin Schuman and Oswald Steward for the discovery of local protein translation in neurons and establishing its importance for brain development and plasticity."  

The same page has a video announcement, where someone very incorrectly makes the utterly groundless claim at the 16:32 mark that this research "came to transform our understanding of how the brain develops, adapts, and stores information." Neuroscientists have no real understanding of how a brain can store learned information, and the vague hand-waving simple-slogan "theory" of synapse strengthening is no such understanding. The same authority makes the groundless boast at the 18:15 mark that the work of Kelsey Martin "helps explain how learning and memory are stored in the brain," a boast that has no basis in truth. Neuroscientists do not have any understanding of how any learning or memory could be stored in the brain, and microscopic examination of brain tissue has never produced the slightest trace of anything learned or experienced or memorized. 

A Simons Foundation page incorrectly claims this was a reward for memory research, stating, "This year’s Kavli Prize in Neuroscience celebrates research on how neurons form and modify neural connections to enable processes such as learning and memory." That goes beyond any claim made in the written prize announcement statement, and we certainly do not know that "neural connections...enable processes such as learning and memory," which is a mere groundless dogma of neuroscientists. 

A press release by the University of California announcing this prize gives us bunk and misleading information related to this topic. We have a press release with this paragraph, preceded by the bogus header of "Transformative discoveries." The paragraph veers into falsehood at its end:

"For decades, scientists believed that proteins needed by neurons were produced primarily in the cell body. Steward’s groundbreaking electron microscopy studies revealed protein-producing machinery located near synapses, which is where cells make connections with each other, demonstrating that neurons can manufacture proteins locally where they’re needed. His subsequent research defined the mechanisms of messenger RNA transport from the nucleus and selective localization at active synapses, creating a new understanding of brain plasticity, learning and memory." 

The described research produced no actual progress in understanding learning or memory. Neuroscientists claim that protein synthesis is required for learning and memory, but their claims about this do not hold up to scrutiny, because of two reasons:

(1) All brain proteins have short lifetimes, typically less than two weeks. The proteins in the brain and its synapses are constantly being replaced. There is no credibility in attempts to explain memory formation by referring to "synapse strengthening" occurring by protein synthesis. Old humans can remember well things that happened 50 years ago, and the span of 50 years is a length of time 1000 times greater than the average lifetime of the proteins in synapses. Individual synapses cannot last for years, partially because they are connected to dendritic spines that do not last for years, and typically last for less than a few months. 

(2) Humans can learn things instantly, much faster than the time required for synapse strengthening by protein synthesis, which is at least several minutes. When someone is informed of the death of their child or parent, that person instantly forms a new memory that lasts for the rest of his life. 

It seems, therefore, that mere research into protein synthesis can never correctly be described as research that helps understand how memories form. A press release at the University of Cambridge has a paragraph that describes the research awarded the Kavli prize in neuroscience, and attempts to create some impression that a little progress has occurred related to understanding memory. But the narrative it tells is a false one, and the paragraph starts out with a misleading first sentence. The paragraph is below:

"Scientists long struggled to explain how the human brain can be so efficient – we can ultimately learn things in mere minutes. The proteins needed to enable the process in brain cells simply take too long to travel from the body of the brain cell, the neuron, to where the synapses – tiny junctions between neurons that allow them to communicate with each other or other cells – actually happen. But research spanning decades by this year’s laureates – Oswald Steward, Erin Schuman, Kelsey Martin and Christine Holt – has solved the mystery. Rather than the proteins being created in the cell body, as was previously thought, they can be produced directly on site close to where the all-important synapses happen; in the branches of the neurons appendages, called dendrites and axons. The discovery has led to a new understanding of how the brain works – and offers insights into how this process goes wrong in a range of brain disorders."

The narrative is bogus. It begins with the very misleading insinuation that human memory creation requires minutes. To the contrary, humans can form new memories instantly. So there was never a "problem of explaining how memories can be created in mere minutes." The problem was a much more difficult one: the problem of explaining how humans can create complex new memories instantly. 

The real problem (the problem of how humans can create complex new memories instantly) is not at all solved (or even appreciably reduced) by postulating that proteins are synthesized in the dendrites of cells, and are then used to bulk up synapses. The diagram below may help you understand why:

What difference would it make (under the theory that memories are stored in synapses) if some proteins are synthesized in dendrites  (the rather finger-like projections you see in the diagram above) rather than in the cell body of a neuron (surrounding the largest yellow circle in the diagram above)? Very little difference indeed. There might be a very slight decrease in the amount of time it would take newly synthesized proteins to travel to a synapse. But the difference would be small. 

A particular type of protein molecule is created by this process:

(1) Somehow the right position is found in human DNA, allowing a reading to occur from a small fraction of the DNA (called a gene), with the information being transferred into a messenger RNA molecule. How that messenger RNA is ever able to find the right gene is a mystery. The gene stores symbolic information describing the amino acid sequence of some particular protein molecule. This reading is called transcription, and occurs at a rate between 10 and 50 nucleotides per second. Since an average protein requires between 1200 and 1500 nucleotides to be read from a gene for the transcription required by the protein to occur, the transcription of a protein requires somewhere between 25 seconds and several minutes.  

(2) Somehow the messenger RNA molecule is translated into a chain of amino acids. This process is called translation, and is thought to occur at a rate of about 5 amino acids per second. Because the average protein used in synapses has about 450 amino acids, this translation must take an average of roughly 90 seconds. 

(3) Somehow (in a way that is not understood at all) that amino acid sequence quickly converts into a three-dimensional protein molecule that is folded.  This process is called protein folding. How it occurs is a mystery called the protein folding problem, which has not yet been solved. A year 2026 paper states, "The protein folding problem remains unsolved."

The Google Gemini infographic below illustrates this process:

To calculate the time required for a new protein to be created and then travel to a synapse as part of some synapse strengthening imagined to be part of a theoretical storage of memory in synapses, assuming protein synthesis in the main body of a neuron, you would need to calculate all of these different factors:

(1) The time needed for some sensory signal to travel to some neuron so that protein synthesis is somehow triggered (no one has any understanding of how sensory information could have any relation to when or where protein synthesis occurs). 

(2) The time required for a cell or messenger RNA molecule to find the right position in DNA  from which to read the amino acid sequence needed to make the new protein molecule of a particular type. Given that DNA stores the amino acid sequences of more than 20,000 different proteins, without any kind of indexing system or sorting system,  this is kind of a "finding a needle in a haystack" situation. The mere "finding the right location to read" part should take very significant time.

(3) The time needed for the reading to occur once the right location had been found, resulting in a messenger RNA molecule matching the gene read. This is the speed of transcription.  Transcription occurs at a rate between 10 and 50 nucleotides per second. Since an average protein requires between 1200 and 1500 nucleotides to be read from a gene for the transcription required for that protein to occur, the transcription of a protein requires somewhere between 25 seconds and several minutes.  

(4) The time required for protein translation, by which the messenger RNA molecule is converted into an amino acid sequence, a specific chain of hundreds of amino acids. Translation in humans is thought to occur at a rate of about 5 amino acids per second. Because the average protein used in synapses has about 450 amino acids, this translation must take an average of roughly 90 seconds.

(5) The time required for there to occur the mysterious process of protein folding, by which a chain of amino acids forms into the 3D shape needed for a functional protein molecule.  

(6) The time needed for a newly synthesized protein molecule to travel from the neuron to the synapse. 

(7) The time needed for this newly synthesized protein molecule to somehow be integrated into the synapse, so that the synapse ends up being strengthened.

The total length of time required for this series of events would be at least three minutes, and very probably many minutes. You only slightly reduce the total length of time required for the totality of all of these things if you assume some protein synthesis going on in dendrites. That reduces the time required for only one of the items in the list above, leaving all of the other factors being just as slow as before.  

Because synapse strengthening requires a series of events that would require a total time of at least three minutes, the synaptic theory of memory (that memories are stored by synaptic strengthening) totally fails to account for the indisputable reality that humans can form permanent new memories instantly. Very rich organizations such as the Kavli Foundation can issue all of the triumphal million-dollar prize announcements that they wish. But the fact is that scientists do not have any credible explanation for how there could occur in a brain human learning which occurs instantly. The most reasonable alternative here is to discard the dogma that memory formation is a brain process. 

Synapses have not the slightest resemblance to a memory storage device. The idea that human memory can be explained by some mere idea of synapse strengthening is one that future scientists will look back on with scorn, the way today's scientists look back scornfully at 18th-century claims that health could be improved by attaching leeches to the arm. Strengthening isn't storage.