Cognitive Interdependence in Close Relationships

This chapter is concerned with the thinking processes of the intimate dyad. So, although we wlll focus from time to time on the thinking processes of the individual - as they influence and are influenced by the relationship with another person - our prime interest is in thinking as it occurs at the dyadic level. This may be dangerous territory for inquiry. After all, this topic resembles one that has, for many years now, represented something of a "black hole" in the social sciences - the study of the group mind. For good reasons, the early practice of drawing an analogy between the mind of the individual and the cognitive operations of the group has long been avoided, and references to the group mind in contemporary literature have dwindled to a smattering of wisecracks. 

Why, then, would we want to examine cognitive interdependence in close relationships? Quite simply, we believe that much could be learned about intimacy in this enterprise, and that a treatment of this topic, enlightened by the errors of past analyses, is now possible. The debate on the group mind has receded into history sufficiently that its major points can be appreciated, and at the same time, we find new realms of theoretical sophistication in psychology regarding the operation of the individual mind. With this background, we believe it is possible to frame a notion somewhat akin to the "group mind" and we to use it to conceptualize how people in close relationships may depend on each other for acquiring, remembering, and generating knowledge.

Interdependent Cognition 

Interdependence is the hallmark of intimacy. Although we are all interdependent to a certain degree, people in close relationships lead lives that are intertwined to the extreme. Certainly, the behaviors they enact, the emotions they feel, and the goals they pursue are woven in an intricate web. But on hearing even the simplest conversation between intimates, it becomes remarkably apparent that their thoughts, too, are interconnected. Together, they think about things in ways they would not alone. The idea that is central in our analysis of such cognitive interdependence is what we term transactive memory. As will become evident, we find this concept more clearly definable and, ultimately, more useful than kindred concepts that populate the history of social psychology. As a preamble to our ideas on transactive memory, we discuss the group mind notion and its pitfalls. We then turn to a concern with the basic properties and processes of transactive memory. [...]

The Nature of Transactive Memory 

Ordinarily, psychologists think of memory as an individual's store of knowledge, along with the processes whereby that knowledge is constructed organized, and accessed. So, it is fair to say that we are studying "memory'; when we are concerned with how knowledge gets into the person's mind, how it is arranged in the context of other knowledge when it gets there, and how it is retrieved for later use. At this broad level of definition, our conception of transactive memory is not much different from the notion of individual memory. With transactive memory, we are concerned with how knowledge enters the dyad, is organized within it, and is made available for subsequent use by it. This analogical leap is a reasonable one as long as we restrict ourselves to considering the functional equivalence of individual and transactive memory. Both kinds of memory can be characterized as systems that, according to general system theory (von Bertalanffy, 1968), may show rough parallels in their modes of operation. Our interest is in processes that occur when the transactive memory system is called upon to perform some function for the group - a function that the individual memory system might reasonably be called upon to perform for the person. 

Transactive memory can be defined in terms of two components: (1) an organized store of knowledge that is contained entirely in the individual memory systems of the group members, and (2) a set of knowledge-relevant transactive processes that occur among group members. Stated more colloquially, we envision transactive memory to be a combination of individual minds and the communication among them. This definition recognizes explicitly that transactive memory must be understood as a name for the interplay of knowledge, and that this interplay, no matter how complex, is always capable of being analyzed in terms of communicative events that have individual sources and individual recipients. By this definition, then, the thought processes of transactive memory are completely observable. The various communications that pass between intimates are, in principle, observable by outside observers just as each intimate can observe the communications of the other. Using this line of intepretation, we recognize that the observable interaction between individuals entails not only the transfer of knowledge, but the construction of a knowledge-acquiring, knowledge-holding, and knowledge-using system that is greater than the sum of its individual member systems. 

Let us consider a simple example to bring these ideas down to earth. Suppose we are spending an evening with Rudy and Lulu, a couple married for several years. Lulu is in another room for the moment, and we happen to ask Rudy where they got the wonderful stuffcd Canadian goose on the mantle. He says, "we were in British Columbia..." and then bellows, "Lulu! What was the name of that place where we got the goose?" Lulu returns to the room to say that it was near Kelowna or Penticton - somewhere along Lake Okanogan. Rudy says, "Yes, in that area with all the fruit stands." Lulu finally makes the identification: Peachland. In all of this, the various ideas that Rudy and Lulu exchange lead them through their individual memories. In a process of interactive cueing, they move sequentially toward the retrieval of a memory trace, the existence of which is known to both of them; And it is just possible that, without each other, neither Rudy nor Lulu could have produced the item. This is not the only process of transactive memory. Although we will speak of interactive cueing again, it is just one of a variety of communication processes that operate on knowledge in the dyad. Transactive processes can occur during the intake of information by the dyad, they can occur after information is stored and so modify the stored information, and they can occur during retrieval. 

The successful operation of these processes is dependent, however, on the formation of a transactive memory structure - an organizational scheme that connects the knowledge held by each individual to the knowledge held by the other. It is common in theorizing about the thoughts and memories of individuals to posit an organizational scheme that allows the person to connect thoughts with one another - retrieving one when the other is encountered, and so forth. In a dyad, this scheme is complicated somewhat by the fact that the individual memory stores are physically separated. Yet it is perfectly reasonable to say that one partner may know, at least to a degree, what is in the other's memory. Thus, one's memory is "connected" to the other's, and it is possible to consider how information is arranged in the dyadic system as a whole. A transactive memory structure thus can be said to reside in the memories of both individuals - when they are considered as a combined system. 

We should point out here that transactive processes and structures are not exclusively the province of intimate dyads. We can envision these: things occurring as well in pairs of people who have just met, or even in groups of people larger than the dyad. At the extreme, one might attribute these processes and organizational capacities to whole societies, and so make transactive memory into a synonym for culture. Our conceptualization stops short or these extensions for two reasons. First, we hesitate to extend these ideas to larger groups because the analysis quickly becomes unwieldy; our framework for understanding transactive memory would need to expand geometrically as additional individuals were added to the system. Second, we refrain from applying this analysis to nonintimate relations for the simple reason that, in such dyads, there is not as much to be remembered. Close dyads share a wealth of information unique to the dyad, and use it to operate as a unit. More distant dyads; in turn, engage in transactive processes only infrequently - and in the case of a first and only encounter, do so only once. Such pairs will thus not have a very rich organizational scheme for information they hold. We find the notion of transactive memory most apt, in sum, for the analysis of cognitive interdependence in intimate dyads. 

Our subsequent discussion of transactive memory in this chapter is fashioned to coincide with the process-structure distinction. We begin by considering the processes involved in the everyday operation of transactive memory. Here, we examine the phases of knowledge processing standardly recognized in cognitive psychology - encoding, storage, and retrieval - to determine how they occur in transactive memory. The second general section examines the nature of the organizational structure used for the storage of information in the dyad. The structure of stored information across the two individual memories will be examined, with a view toward determining how this organization impinges on the group's mental operations. The final section concentrates on the role of transactive memory, both process and structure, in the life of the dyad. We consider how such memory may contribute to compatibility or incompatibility in relationships, and how an individual's personal memory may be influenced by membership in a transactive system. 

Transactive Memory Processes 

Communication is the transfer of information. When communication takes place between people, we might say that information is transferred from one memory to another. However, when the dyadic group is conceptualiized as having one memory system, interpersonal communication in the dyad comes to mean the transfer of information within memory. We believe that multiple transfers can occur as the dyad encodes information, as it holds information in storage, and as it retrieves information - and that such transfers can make each of these processes somewhat different from its counterpart occurring at the individual level.

Transactive Encoding 

Obviously, dyads do not have their sense organs in common. The physical and social environment thus must be taken in by each person separately. Social theorists have repeatedly noted, though; that an individual's perceptions can be channeled in social ways. Many have observed, for example, that one partner might empathize with another and see the world from the other's "point of view." Alternatively, cognitive constructions of a "group perspective" may be developed by both partners that lend a certain commonality to their intake of information (see Wegner & Giuliano, 1982). These social influences on encoding, however, are best understood as effects on the individual. How does the dyad encode information? 

When partners encounter some event and encode it privately in their individual memories, they may discuss it along the way. And though we might commonly think of such a discussion as a "rehash," a mere echo of the original perceived event, there is reason to think that it could be much more. After all whereas expeiencing an event can be accomplished quite passively, discussing an event requires active processing of the information - and the generation of ideas relevant to the event. Several demonstrations of an individual memory phenomenon called the "generation effect" indicate that people will often remember information they have generated better than information they have simply experienced. So, for instance, one might remember the number 37 better if one had been presented with "14 + 23 = ?" than if one had merely been presented with "37 ." Partners who talk over an event, generating information along the way, might thus come to an encoded verbal representation of the event that supplants their original, individual encoding. 

The influence of the generation effect could, of course, take many forms. Ordinarily, it should lead partners to remember their own contributions to dyadic discussions better than the contributions of their partners. This phenomenon has been observed in several studies (e.g., Ross & Sicoly, 1979). But the generation effect could also contribute to one's memory for group generated information. When a couple observes some event - say, a wedding they may develop somewhat disparate initial encodings. Each will understand that it was indeed a wedding; but only one may encode the fact that the father of the bride left the reception in a huff; the other might notice instead the odd, cardboard-like flavor of the wedding cake. Their whispered chat during all this could lead them to infer that the bride's father was upset by the strange cake. Because this interpretation was generated by the group, both partners will have thus encoded the group's understanding of the events. Their chat could thus revise history for the group, leaving both with stored memories of the father angry over a sorry cake. 

Evidence from another domain of cognitive research leads to a similar point. One of the most powerful determinants of encoding in individual memory is the degree to which the incoming information is semantically elaborated (e.g., Anderson & Reder, 1979). To elaborate incoming information is simply to draw inferences from it and consider its meaning in relation to other information. This is precisely what happens in dyadic communications about events. Partners often talk about things they have experienced as individuals or as a group. They may speak about each other's behavior, about the behavior of others they both know, about the day's events, and so on. In such discussions, it is probable that those particular events or behaviors relevant to the dyad will be discussed at length. They will be tied to other items of knowledge and, in the process, will become more elaborately encoded - and thus more likely to be available for later retrieval. 

To the extent that generative or elaborative processes are effortful, or require careful thinking, their effects could be strengthened yet further. Encoding processes that are effortful for the individual typically lead to enhanced memory. When a couple engages in an argument, cognitive effort may be required for each person to understand what the other is saying and for each to convey a personal point of view. Such effort on the part of both could also be necessary when one partner is merely trying to teach the other something. It is the shared experience of argument, decision-making, or careful analysis that will be remembered more readily when the communication is effortful. After all, couples more frequently remember their "talks" than their routine dinner conversations. 

These transactive encoding processes could conceivably lead a dyad to understand events in highly idiosyncratic and private ways. Their discussions could go far afield, linking events to knowledge that, while strongly relevant to the dyad, is embedded primarily in the dyad's known history or anticipated future. The partners' memories of the encoded events themselves could be changed dramatically by the tenor of their discussions, sometimes to the point of losing touch with the initial realities the partners perceived. To some degree, such departures from originally encoded experience might be corrected by the partners' discussions' of events with individuals outside the relationship; such outsiders would serve to introduce a perspective on events that is uninformed of the dyad's concerns, and that therefore might help to modify memory of the events. But many experiences are discussed only within the relationship, and these are thus destined to be encoded in ways that may make them more relevant to the dyad's concerns than to the realities from which they derived.

by Daniel M Wegner, Toni Giuliano, and Paula T. Hertel, Harvard |  Read more (pdf):

Image via:

[ed. Probably of little interest to most but I find this, and the process of memory retrieval in general, to be fascinating. When I think back on the various experiences and conversations I've had over my lifetime it's not uncommon to settle on the same scenes, arguments, feelings, etc. over and over again to represent what I remember as being reality, or at least an accurate reflection of my personal 'history', when actually they're just a small slice of a larger picture, taken out of context. Want an example? Try talking to an old friend at a class reunion and see what they recall about your experiences together. We can never remember all the details of the thousands of small conversations and experiences we've had - individually, with partners, with others - that in the aggregate have more relevance to reality than we can imagine... or remember.]

Tomorrow’s Smart Pills Will Deliver Drugs and Take Biopsies

One day soon, a doctor might prescribe a pill that doesn’t just deliver medicine but also reports back on what it finds inside you—and then takes actions based on its findings.

Instead of scheduling an endoscopy or CT scan, you’d swallow an electronic capsule smaller than a multivitamin. As it travels through your digestive system, it could check tissue health, look for cancerous changes, and send data to your doctor. It could even release drugs exactly where they’re needed or snip a tiny biopsy sample before passing harmlessly out of your body.

This dream of a do-it-all pill is driving a surge of research into ingestible electronics: smart capsules designed to monitor and even treat disease from inside the gastrointestinal (GI) tract. The stakes are high. GI diseases affect tens of millions of people worldwide, including such ailments as inflammatory bowel disease, celiac disease, and small intestinal bacterial overgrowth. Diagnosis often involves a frustrating maze of blood tests, imaging, and invasive endoscopy. Treatments, meanwhile, can bring serious side effects because drugs affect the whole body, not just the troubled gut.

If capsules could handle much of that work—streamlining diagnosis, delivering targeted therapies, and sparing patients repeated invasive procedures—they could transform care. Over the past 20 years, researchers have built a growing tool kit of ingestible devices, some already in clinical use. These capsule-shaped devices typically contain sensors, circuitry, a power source, and sometimes a communication module, all enclosed in a biocompatible shell. But the next leap forward is still in development: autonomous capsules that can both sense and act, releasing a drug or taking a tissue sample.

That’s the challenge that our lab—the MEMS Sensors and Actuators Laboratory (MSAL) at the University of Maryland, College Park—is tackling. Drawing on decades of advances in microelectromechanical systems (MEMS), we’re building swallowable devices that integrate sensors, actuators, and wireless links in packages that are small and safe enough for patients. The hurdles are considerable: power, miniaturization, biocompatibility, and reliability, to name a few. But the potential payoff will be a new era of personalized and minimally invasive medicine, delivered by something as simple as a pill you can swallow at home. [...]

Targeted drug delivery is one of the most compelling applications for ingestible capsules. Many drugs for GI conditions—such as biologics for inflammatory bowel disease—can cause serious side effects that limit both dosage and duration of treatment. A promising alternative is delivering a drug directly to the diseased tissue. This localized approach boosts the drug’s concentration at the target site while reducing its spread throughout the body, which improves effectiveness and minimizes side effects. The challenge is engineering a device that can both recognize diseased tissue and deliver medication quickly and precisely.

With other labs making great progress on the sensing side, we’ve devoted our energy to designing devices that can deliver the medicine. We’ve developed miniature actuators—tiny moving parts—that meet strict criteria for use inside the body: low power, small size, biocompatibility, and long shelf life.

Some of our designs use soft and flexible polymer “cantilevers” with attached microneedle systems that pop out from the capsule with enough force to release a drug, but without harming the intestinal tissue. While hollow microneedles can directly inject drugs into the intestinal lining, we’ve also demonstrated prototypes that use the microneedles for anchoring drug payloads, allowing the capsule to release a larger dose of medication that dissolves at an exact location over time.

In other experimental designs, we had the microneedles themselves dissolve after injecting a drug. In still others, we used microscale 3D printing to tailor the structure of the microneedles and control how quickly a drug is released—providing either a slow and sustained dose or a fast delivery. With this 3D printing, we created rigid microneedles that penetrate the mucosal lining and gradually diffuse the drug into the tissue, and soft microneedles that compress when the cantilever pushes them against the tissue, forcing the drug out all at once.

by Reza Ghodssi, Justin Stine, Luke Beardslee, IEEE Spectrum |  Read more:

Image: Maximilian Franz/Engineering at Maryland Magazine

Jimi Hendrix Was a Systems Engineer

Jimi Hendrix Was a Systems Engineer. He precisely controlled modulation and feedback loops (IEEE Spectrum).

Image: James Provost

[ed. Everything was new and primitive back then. Jimi pushed these new tools to their limits.]

Embryo Selection Company Herasight Goes All In On Eugenics

Multiple commercial companies are now offering polygenic embryo selection on a wide range of traits, including genetic predictors of behavior and IQ. I’ve previously written about the methodological unknowns around this technology but I haven’t commented on the ethics. I think having a child is a very personal decision and it’s not my place to tell people how to do it. But the new embryo selection company, Herasight, has started advocating for eugenic societal norms that I find disturbing and worth raising alarm over. Because this is a fraught topic, I’ll start with some basic definitions.

What is eugenics?

Eugenics is an ideology that advocates for conditioning reproductive rights on the perceived genetic quality of the parents. Francis Galton, the father of eugenics, declared that eugenics’ “first object is to check the birth-rate of the Unfit, instead of allowing them to come into being”. This goal was to be achieved through social stigma and, if necessary, by force. The Eugenics Education Society, for instance, advocated for education, segregation, and — “perhaps” — compulsory sterilization to prevent the “unfit and degenerate” from reproducing:

A core component of defining “the unfit” was heredity. Eugenicists are not just interested in improving people’s phenotypes — a goal that is widely shared by modern society — but the future genotypic distribution. The genetic stock. This is why eugenic policies historically focus on sterilization, including the sterilization of unaffected relatives who harbor genotype but not phenotype. If someone commits a crime, they face time in prison for their actions, but under eugenic reasoning their law-abiding sibling or child is also suspect and should be stigmatized (or forcefully prevented) from passing on deficient genetic material.

A simple two-part test for eugenics is then: (1) Is it concerned with the future genetic stock? (2) Is it advocating for restricted reproduction, either through stigma or force, for those deemed genetically inferior?

Is embryo selection eugenics?

I have publicly resisted applying the “eugenics” label to embryo selection writ large and I continue to do so. Embryo selection is a tool and its use is morally complex. A couple can choose to have embryo screening for a variety of reasons ranging from frivolous (“we want to have a blue eyed baby”) to widely supported (“we carry a recessive mutation that would be fatal in our baby”), none of which have eugenic intent. Embryo selection can even be an anti-eugenic tool, as in the case of high-risk couples who have already decided against having children. If embryo selection technology allows them to lower the risk to a comfortable level and have a child they would otherwise have avoided, then the outcome is literally the opposite of eugenic selection: “unfit” individuals (at least as they see themselves) now have an incentive to produce more offspring than they would have. In practice, IVF remains a physically and emotionally demanding procedure, and my guess is that individual eugenic intentions — the desire to select out unfit embryos with the specific motivation of improving the “genetic stock” of the population — are exceedingly rare.

Is Herasight advocating for eugenics?

While I do not think embryo selection is eugenic in itself, like any reproductive technology, it can be wielded for eugenic purposes. The new embryo selection company Herasight, in my opinion, is advocating for exactly that. To understand why, it is useful to first understand the theories put forth by Herasight’s director of scientific research and communication Jonathan Anomaly (in case you’re wondering, that is a chosen last name). Anomaly is a self-proclaimed eugenicist [Update: Anomaly has clarified that this description was not provided by him and he requested that it be removed]:

Prior to joining Herasight, Anomaly wrote extensively on the ethics of embryo selection, notably in a 2018 article titled “Defending eugenics”. How does Anomaly defend eugenics? First, he reiterates the classic position that eugenics is a resistance to the uncontrolled reproduction of the “unfit” (emphasis mine, throughout):

Darwin argued that social welfare programs for the poor and sick are a natural expression of our sympathy, but also a danger to future populations if they encourage people with serious congenital diseases and heritable traits like low levels of impulse control, intelligence, or empathy to reproduce at higher rates than other people in the population. Darwin feared that in developed nations “the reckless, degraded, and often vicious members of society, tend to increase at a quicker rate than the provident and generally virtuous members”

Anomaly goes on to sympathize with Darwin’s position and that of the classic eugenicists, arguing that “While Darwin’s language is shocking to contemporary readers, we should take him seriously”, later that “there is increasingly good evidence that Darwin was right to worry about demographic trends in developed countries”, and that we should “stop allowing [the Holocaust] to silence any discussion of the merits of eugenic thinking”.

Anomaly then proposes several potential eugenic interventions, one of which is a “parental licensing” scheme that prevents unfit parents from having children:

The typical response is for the state to step in and pay for all of these things, and in extreme cases to remove children from their parents and put them in foster care. But it would be more cost-effective to prevent unwanted pregnancies than treating their consequences, especially if we could achieve this goal by subsidizing the voluntary use of contraception. It may also be more desirable from the standpoint of future people.

The phrase “future people” figures repeatedly in Anomaly’s writing as a euphemism for the more conventional eugenic concept of genetic stock. This connection is made explicit when he explains the most compelling reason for supporting parental licensing:

The most compelling reason (though certainly not a decisive reason) for supporting parental licensing is that traits like impulse control, health, intelligence, and empathy have significant genetic components. What matters is not just that some parents are unwilling or unable to take care of their children; but that in many cases they are passing along an undesirable genetic endowment.

What are we really talking about here? Anomaly has proposed a technocratic rebranding of eugenic sterilization: instead of taking away your reproductive rights clinically, the state will take away your reproductive license and, if you still have children, impose “fines or other costs” (though Anomaly does not make the “other costs” explicit, eugenic sterilization is mentioned as an example in the very next sentence). How would the state decide who should lose their license? Anomaly explains:

For a parental licensing scheme to be fair, we would need to devise criteria that are effective at screening out only parents who impose significant risks of harm on their children or (through their children) on other people.

A fundamental normative principle of our society is that all members are created equal and endowed with unalienable rights. What Anomaly envisions instead is a society where the state can seize one of the most intimate of human freedoms — the right to become a parent — based on innate factors. How does the state determine whether a future child imposes significant risk on future people? By inspecting the biological makeup of the parents and identifying “undesirable genetic endowments” that will harm others “through their children”. This is a policy built explicitly on genetic desirability and undesirability, where those deemed genetically unfit are stripped of their rights to have children and/or fined for doing so — aka bog-standard coercive eugenics.

Today, Anomaly is the spokesperson for a company that screens parents for “undesirable genetic endowments” and, for a price, promises to boost their genetic desirability and their value to future people. It is easy to see how Herasight fits directly into the eugenic parental licensing scheme Anomaly proposed. Having an open eugenicist as the spokesperson for an embryo selection company seems, to me, akin to hiring Hannibal Lecter to do PR for a hospital, but perhaps Anomaly has radically changed his views since billing himself as a eugenicist in 2023?

Herasight (with Anomaly as first author) recently published a perspective white-paper on the ethics polygenic selection, from which we can glean their corporate position. The perspective outlines the potential benefits and harms of embryo selection. The very first positive benefit listed? The “benefits to future people”. While this section starts with a focus the welfare of individual children, it ends with the same societal motivations as classical eugenics: the social costs of the unfit on communities and the benefits of the fit to scientific innovation and the public good: [...]

When eugenics goes mainstream

Let’s review: eugenics has as a goal of limiting the birthrate of the “unfit” or “undesirable” for the benefit of the group. Anomaly describes himself as a eugenicist and explicitly echoes this goal through, among other policies, a parental licensing proposal. Anomaly now runs a genetic screening company. The company recently published a perspective paper advocating for the stigmatization of “unfit” parents who do not screen. Anomaly, as spokesperson, reiterates that their goal is indeed eugenics — “Yes, and it’s great!”. With any other person one could argue that they were clueless or trolling; but if anyone knows what eugenics means, it is a person who has spent the past decade defending it.

I have to say I am floored by how strange this all is. My personal take on embryo selection has been decidedly neutral. I think the expected gains are limited by the genetic architecture of the traits being scored and the companies are mostly fudging the numbers to look good. As noted above, I also think a common use of this technology will be to calm the nerves of parents who otherwise would have gone childless. So I have no actual concerns about changes to the genetic make-up of the population or genetic inequality or any of the other utopian/dystopian predictions. But I am concerned that the marketing around the technology revives and normalizes classic eugenic arguments: that society is divided into the genetically fit and the genetically unfit, and the latter need to be stigmatized away from parenthood for the benefit of the former. I am particularly disturbed by the giddiness with which Anomaly and Herasight have repeatedly courted eugenics-related controversy as part of their launch campaign.

Even stranger has been the response, or rather non-response, from the genetics community. Social science geneticists and organizations spent the past decade writing FAQs warning against the use of their methods and data for individual prediction and against genetic essentialism. Many conference presentations and seminars start with a section on the sordid history of eugenics and the sterilization programs in the US and Nazi Germany, vowing not to repeat the mistakes of the past. Now, a company is openly advocating for eugenics (in fact, a company with direct connections to these social science organizations) and these organizations are silent. It is hard not to conclude that the FAQs and warnings were just lip service. And if the experts aren’t raising alarms, why would the public be alarmed?

by Sasha Gusev, The Infinitesimal |  Read more:

Image: Anselm Kiefer, Die Ungeborenen (The Unborn), 2002

[ed. With neophyte Nazis seemingly everywhere these days, CRISPR advances, and technocrats who want to live forever, it's perhaps not surprising that eugenics would be making a comeback. Update: Jonathan Anomaly, director of scientific research and communication for Herasight and whose articles I criticize here, responds in a detailed comment. I recommend reading his response together with this post. Anomaly’s role in the company has also been clarified. See also: Have we leapt into commercial genetic testing without understanding it? (Ars Technica).]

Your Job Isn't Disappearing. It's Shrinking Around You in Real Time

You open your laptop Monday morning with a question you can’t shake: Will I still have a job that matters in two years?

Not whether you’ll be employed, but whether the work you do will still mean something.
Last week, you spent three hours writing a campaign brief. You saw a colleague generate something 80% as good in four minutes using an AI agent (Claude, Gemini, ChatGPT…). Maybe 90% as good if you’re being honest.

You still have your job. But you can feel it shrinking around you.

The problem isn’t that the robots are coming. It’s that you don’t know what you’re supposed to be good at anymore. That Excel expertise you built over five years? Automated. Your ability to research competitors and synthesize findings? There’s an agent for that. Your skill at writing clear project updates? Gone.

You’re losing your professional identity faster than you can rebuild it. And nobody’s telling you what comes next.

The Three Things Everyone Tries That Don’t Actually Work

When you feel your value eroding, you do what seems rational. You adapt, you learn, and you try to stay relevant.

First, you learn to use the AI tools better. You take courses on prompt engineering. You master ChatGPT, Claude, whatever new platform launches next week and the week after. You become the “AI person” on your team. You think that if I can’t beat them, I’ll use them better than anyone else.

This fails because you’re still competing on execution speed. You’re just a faster horse. And execution is exactly what’s being commoditized. Six months from now, the tools will be easier to use. Your “expertise” in prompting becomes worthless the moment the interface improves. You’ve learned to use the shovel better, but the backhoe is coming anyway.

Second, you double down on your existing expertise. The accountant learns more advanced tax code. The designer masters more software. The analyst builds more complex models. You will have the same thought as many others, “I’ll go so deep they can’t replace me.”

This fails because depth in a disappearing domain is a trap. You’re building a fortress in a flood zone. Agents aren’t just matching human expertise at the median level anymore. They’re rapidly approaching expert-level performance in narrow domains. Your specialized knowledge becomes a liability because you’ve invested everything in something that’s actively being automated. You’re becoming the world’s best telegraph operator in 1995.

Third, you try to “stay human” through soft skills. You lean into creativity, empathy, relationship building. You go to workshops on emotional intelligence. You focus on being irreplaceably human. You might think that what makes us human can’t be automated.

This fails because it’s too vague to be actionable. What does “be creative” actually mean when an AI can generate 100 ideas in 10 seconds? How do you monetize empathy when your job is to produce reports? The advice feels right but provides no compass. You end up doing the same tasks you always did, just with more anxiety and a vaguer sense of purpose.

The real issue with all three approaches is that they’re reactions, not redesigns. You’re trying to adapt your old role to a new reality. What actually works is building an entirely new role that didn’t exist before.

But nobody’s teaching you what that looks like.

The Economic Logic Working Against You

This isn’t happening to you because you’re failing to adapt. It’s happening because the economic incentive structure is perfectly designed to create this problem.

The mechanism is simple, companies profit immediately from adopting AI agents. Every task automated results in cost reduction. The CFO sees the spreadsheet, where one AI subscription replaces 40% of a mid-level employee’s work. The math is simple, and the decision is obvious.

Many people hate to hear that. But if they owned the company or sat in leadership, they’d do the exact same thing. Companies exist to drive profit, just as employees work to drive higher salaries. That’s how the system has worked for centuries.

But companies don’t profit from retraining you for a higher-order role that doesn’t exist yet.

Why? Because that new role is undefined, unmeasured, and uncertain. You can’t put “figure out what humans should do now” on a quarterly earnings call. You can’t show ROI on “redesign work itself.” Short-term incentives win. Long-term strategy loses.

Nobody invests in the 12-24 month process of discovering what your new role should be because there’s no immediate return on that investment.

We’re in a speed mismatch. Agent capabilities are compounding at 6-12 month cycles. [ed. Even faster now, after the release of Claude Opus 4.6 last week]. Human adaptation through traditional systems operates on 2-5 year cycles.

Universities can’t redesign curricula fast enough. They’re teaching skills that will be automated before students graduate. Companies can’t retrain fast enough. By the time they identify the new skills needed and build a program, the landscape has shifted again. You can’t pivot fast enough. Career transitions take time. Mortgages don’t wait.

We’ve never had to do this before.

Previous automation waves happened in manufacturing. You could see the factory floor. You could watch jobs disappear and new ones emerge. There was geographic and temporal separation.

This is different, knowledge work is being automated while you’re still at your desk. The old role and new role exist simultaneously in the same person, the same company, the same moment.

And nobody has an economic incentive to solve it. Companies maximize value through cost reduction, not workforce transformation. Educational institutions are too slow and too far removed from real-time market needs. Governments don’t understand the problem yet. You’re too busy trying to keep your current job to redesign your future one.

The system isn’t helping because it isn’t designed for continuous, rapid role evolution; it is designed for stability.

We’re using industrial-era institutions to solve an exponential-era problem. That’s why you feel stuck.

Your Experience Just Became Worthless (The Timeline)

Let me tell you a story of my friend, let’s call her Jane (Her real name is Katřina, but the Czech diacritic is tricky for many). She was a senior research analyst at a mid-sized consulting firm. Ten years of experience. Her job was provide answers to the client companies, who would ask questions like “What’s our competitor doing in the Asian market?” and she’d spend 2-3 weeks gathering data, reading reports, interviewing experts, synthesizing findings, and creating presentations.

She was good, clients loved her work, and she billed at $250 an hour.

The firm deployed an AI research agent in Q2 2023. Not to replace her, but as they said, to “augment” her. Management said all the right things about human-AI collaboration.

The agent could do Jane’s initial research in 90 minutes, it would scan thousands of sources, identify patterns, generate a first-draft report.

Month one: Jane was relieved and thought she could focus on high-value synthesis work. She’d take the agent’s output and refine it, add strategic insights, make it client-ready.

Month three: A partner asked her, “Why does this take you a week now? The AI gives us 80% of what we need in an hour. What’s the other 20% worth?”

Jane couldn’t answer clearly. Because sometimes the agent’s output only needed light editing. Sometimes her “strategic insights” were things the agent had already identified, just worded differently.

Month six: The firm restructured. They didn’t fire Jane, they changed her role to “Quality Reviewer.” She now oversaw the AI’s output for 6-8 projects simultaneously instead of owning 2-3 end to end.

Her title stayed the same. Her billing rate dropped to $150 an hour. Her ten years of experience felt worthless.

Jane tried everything. She took an AI prompt engineering course. She tried to go deeper into specialized research methodologies. She emphasized her client relationships. None of it mattered because the firm had already made the economic calculation.

One AI subscription costs $50 a month. Jane’s salary: $140K a year. The agent didn’t need to be perfect; it just needed to be 70% as good at 5% of the cost. But it was fast, faster than her.

The part that illustrates the systemic problem, you often hear from AI vendors that, thanks to their AI tools, people can focus on higher-value work. But when pressed on what that meant specifically, they’d go vague. Strategic thinking, client relationships, creative problem solving.

Nobody could define what higher-value work actually looked like in practice. Nobody could describe the new role. So they defaulted to the only thing they could measure: cost reduction.

Jane left six months later. The firm hired two junior analysts at $65K each to do what she did. With the AI, they’re 85% as effective as Jane was.

Jane’s still trying to figure out what she’s supposed to be good at. Last anyone heard, she’s thinking about leaving the industry entirely.

Stop Trying to Be Better at Your Current Job

The people who are winning aren’t trying to be better at their current job. They’re building new jobs that combine human judgment with agent capability.

Not becoming prompt engineers, not becoming AI experts. Becoming orchestrators who use agents to do what was previously impossible at their level. [...]

You’re not competing with the agent. You’re creating a new capability that requires both you and the agent. You’re not defensible because you’re better at the task. You’re defensible because you’ve built something that only exists with you orchestrating it.

This requires letting go of your identity as “the person who does X.” Marcus doesn’t write copy anymore. That bothered him at first. He liked writing. But he likes being valuable more.

Here’s what you can do this month:

by Jan Tegze, Thinking Out Loud |  Read more:

Image: uncredited

[ed. Not to criticize, but this advice still seems a bit too short-sighted (for reasons articulated in this article: AI #155: Welcome to Recursive Self-Improvement (DMtV):]

***

Presumably you can see the problem in such a scenario, where all the existing jobs get automated away. There are not that many slots for people to figure out and do genuinely new things with AI. Even if you get to one of the lifeboats, it will quickly spring a leak. The AI is coming for this new job the same way it came for your old one. What makes you think seeing this ‘next evolution’ after that coming is going to leave you a role to play in it?

If the only way to survive is to continuously reinvent yourself to do what just became possible, as Jan puts it? There’s only one way this all ends.

I also don’t understand Jan’s disparate treatment of the first approach that Jan dismisses, ‘be the one who uses AI the best,’ and his solution of ‘find new things AI can do and do that.’ In both cases you need to be rapidly learning new tools and strategies to compete with the other humans. In both cases the competition is easy now since most of your rivals aren’t trying, but gets harder to survive over time.

***

[ed. And the fact that there'll be a lot fewer of these types of jobs available. This scenario could be reality within the next year (or less!). Something like a temporary UBI (universal basic income) might be needed until long-term solutions can be worked out, but do you think any of the bozos currently in Washington are going to focus on this? And, that applies to safety standards as well. Here's Dean Ball (Hyperdimensional): On Recursive Self-Improvement (Part II):

***

Policymakers would be wise to take especially careful notice of this issue over the coming year or so. But they should also keep the hysterics to a minimum: yes, this really is a thing from science fiction that is happening before our eyes, but that does not mean we should behave theatrically, as an actor in a movie might. Instead, the challenge now is to deal with the legitimately sci-fi issues we face using the comparatively dull idioms of technocratic policymaking. [...]

Right now, we predominantly rely on faith in the frontier labs for every aspect of AI automation going well. There are no safety or security standards for frontier models; no cybersecurity rules for frontier labs or data centers; no requirements for explainability or testing for AI systems which were themselves engineered by other AI systems; and no specific legal constraints on what frontier labs can do with the AI systems that result from recursive self-improvement.

To be clear, I do not support the imposition of such standards at this time, not so much because they don’t seem important but because I am skeptical that policymakers could design any one of these standards effectively. It is also extremely likely that the existence of advanced AI itself will both change what is possible for such standards (because our technical capabilities will be much stronger) and what is desirable (because our understanding of the technology and its uses will improve so much, as will our apprehension of the stakes at play). Simply put: I do not believe that bureaucrats sitting around a table could design and execute the implementation of a set of standards that would improve status-quo AI development practices, and I think the odds are high that any such effort would worsen safety and security practices.

I Regret to Inform You that the FDA is FDAing Again

I had high hopes and low expectations that the FDA under the new administration would be less paternalistic and more open to medical freedom. Instead, what we are getting is paternalism with different preferences. In particular, the FDA now appears to have a bizarre anti-vaccine fixation, particularly of the mRNA variety (disappointing but not surprising given the leadership of RFK Jr.).

The latest is that the FDA has issued a Refusal-to-File (RTF) letter to Moderna for their mRNA influenza vaccine, mRNA-1010. An RTF means the FDA has determined that the application is so deficient it doesn’t even warrant a review. RTF letters are not unheard of, but they’re rare—especially given that Moderna spent hundreds of millions of dollars running Phase 3 trials enrolling over 43,000 participants based on FDA guidance, and is now being told the (apparently) agreed-upon design was inadequate. [...]

In context, this looks like the regulatory rules of the game are being changed retroactively—a textbook example of regulatory uncertainty destroying option value. STAT News reports that Vinay Prasad personally handled the letter and overrode staff who were prepared to proceed with review. Moderna took the unusual step of publicly releasing Prasad’s letter—companies almost never do this, suggesting they’ve calculated the reputational risk of publicly fighting the FDA is lower than the cost of acquiescing.

Moreover, the comparator issue was discussed—and seemingly settled—beforehand. Moderna says the FDA agreed with the trial design in April 2024, and as recently as August 2025 suggested it would file the application and address comparator issues during the review process.

Finally, Moderna also provided immunogenicity and safety data from a separate Phase 3 study in adults 65+ comparing mRNA-1010 against a licensed high-dose flu vaccine, just as FDA had requested—yet the application was still refused.

What is most disturbing is not the specifics of this case but the arbitrariness and capriciousness of the process. The EU, Canada, and Australia have all accepted Moderna’s application for review. We may soon see an mRNA flu vaccine available across the developed world but not in the United States—not because it failed on safety or efficacy, but because FDA political leadership decided, after the fact, that the comparator choice they inherited was now unacceptable.

The irony is staggering. Moderna is an American company. Its mRNA platform was developed at record speed with billions in U.S. taxpayer support through Operation Warp Speed — the signature public health achievement of the first Trump administration. The same government that funded the creation of this technology is now dismantling it. In August, HHS canceled $500 million in BARDA contracts for mRNA vaccine development and terminated a separate $590 million contract with Moderna for an avian flu vaccine. Several states have introduced legislation to ban mRNA vaccines. Insanity.

The consequences are already visible. In January, Moderna’s CEO announced the company will no longer invest in new Phase 3 vaccine trials for infectious diseases: “You cannot make a return on investment if you don’t have access to the U.S. market.” Vaccines for Epstein-Barr virus, herpes, and shingles have been shelved. That’s what regulatory roulette buys you: a shrinking pipeline of medical innovation.

An administration that promised medical freedom is delivering medical nationalism: fewer options, less innovation, and a clear signal to every company considering pharmaceutical investment that the rules can change after the game is played. And this isn’t a one-product story. mRNA is a general-purpose platform with spillovers across infectious disease and vaccines for cancer; if the U.S. turns mRNA into a political third rail, the investment, talent, and manufacturing will migrate elsewhere. America built this capability, and we’re now choosing to export it—along with the health benefits.

by Alex Tabarrok, Marginal Revolution |  Read more:

Image: Brian Snyder/Reuters

[ed. See also: F.D.A. Refuses to Review Moderna Flu Vaccine (NYT); and, Trump official overruled FDA scientists to reject Moderna’s flu shot (Ars Technica).]

Ultrastructural and Histological Cryopreservation of Mammalian Brains by Vitrification

Abstract

Studies of whole brain cryopreservation are rare but are potentially important for a variety of applications. It has been demonstrated that ultrastructure in whole rabbit and pig brains can be cryopreserved by vitrification (ice-free cryopreservation) after prior aldehyde fixation, but fixation limits the range of studies that can be done by neurobiologists, including studies that depend upon general molecular integrity, signal transduction, macromolecular synthesis, and other physiological processes. We now show that whole brain ultrastructure can be preserved by vitrification without prior aldehyde fixation. Rabbit brain perfusion with the M22 vitrification solution followed by vitrification, warming, and fixation showed an absence of visible ice damage and overall structural preservation, but osmotic brain shrinkage sufficient to distort and obscure neuroanatomical detail. Neuroanatomical preservation in the presence of M22 was also investigated in human cerebral cortical biopsies taken after whole brain perfusion with M22. These biopsies did not form ice upon cooling or warming, and high power electron microscopy showed dehydrated and electron-dense but predominantly intact cells, neuropil, and synapses with no signs of ice crystal damage, and partial dilution of these samples restored normal cortical pyramidal cell shapes. To further evaluate ultrastructural preservation within the severely dehydrated brain, rabbit brains were perfused with M22 and then partially washed free of M22 before fixation. Perfusion dilution of the brain to 3-5M M22 resulted in brain re-expansion and the re-appearance of well-defined neuroanatomical features, but rehydration of the brain to 1M M22 resulted in ultrastructural damage suggestive of preventable osmotic injury caused by incomplete removal of M22. We conclude that both animal and human brains can be cryopreserved by vitrification with predominant retention of ultrastructural integrity without the need for prior aldehyde fixation. This observation has direct relevance to the feasibility of human cryopreservation, for which direct evidence has been lacking until this report. It also provides a starting point for perfecting brain cryopreservation, which may be necessary for lengthy space travel and could allow future medical time travel.

by Gregory M. Fahy, Ralf Spindler, Brian G. Wowk, Victor Vargas, Richard La, Bruce Thomson, Roberto Roa, Hugh Hixon, Steve Graber, Xian Ge, Adnan Sharif, Stephen B. Harris, L. Stephen Coles, bioRxiv |  Read more:

[ed. Uh oh. There are a few brains I'd prefer not to see preserved (...like whoever could pay for this). Which reminds me:]

Did you know: Larry Ellison christened his yacht Izanami for a Shinto sea god, but had to hurriedly rename it after it was pointed out that, when spelled backwards, it becomes “I’m a Nazi”. (next year’s story: Elon Musk renames his yacht after being told that, spelled backwards, it becomes the name of a Shinto sea god). 

Here Come the Beetles

The nearly 100-year-old Wailua Municipal Golf Course is home to more than 580 coconut trees. It’s also one of Kaua‘i’s most visible sites for coconut rhinoceros beetle damage.

Located makai of Kūhiō Highway, trees that would normally have full, verdant leaves are dull and have V-shaped cuts in their fronds. Some are bare and look more like matchsticks.

It’s not for lack of trying to mitigate the invasive pest. The trees’ crowns have been sprayed with a pesticide twice, and the trunks were injected twice with a systemic pesticide for longer term protection.

The Kaua‘i Department of Parks & Recreation maintains that even though the trees still look damaged, the treatments are working. Staff have collected 1,679 fallen, dead adult beetles over the last three years.

The most recent treatment, a systemic pesticide that travels through the trees’ vascular systems, was done in January 2025. While crown sprays kill the beetle on contact, systemic pesticides require the beetles to feed from the trees to die. The bugs eat the trees’ hearts — where new fronds develop — so it can take months for foliage damage to appear.

 

“The general public sees these trees that are damaged and thinks, ‘Oh my goodness they’re getting whacked,’ but in actuality, we need them to get whacked to kill (the beetles),” said Patrick Porter, county parks director.

But with the beetles continuing to spread around the island, the county is increasingly turning its attention to green waste, mulch piles and other breeding sites, where beetles spend four to six months growing from eggs to adults. A single adult female beetle can lay up to 140 eggs in her lifetime.

“The reality is if you don’t go after the larvae and you don’t go after your mulch cycle, you’re just pissing in the wind,” said Kaua‘i County Council member Fern Holland. “Because there are just going to be hundreds and hundreds of them hatching all the time, and you can’t go after all of them.” (...)

Last May, the County Council allocated $100,000 for invasive species and another $100,000 for CRB. It was the first time the county designated funds specifically to address the beetle.

Niki Kunioka-Volz, economic development specialist with the Kaua‘i Office of Economic Development, said none of that funding has been spent yet. They’re considering using it to help get the breeding site at the Wailua golf course under control, such as by purchasing an air curtain burner, a fan-powered incinerator of sorts to dispose of green waste. The burner could also be a tool for the broader community. (...)

In 2024, the county received $200,000 from the state Department of Agriculture. That money was used for a CRB outreach campaign, training CRB detection dogs and distributing deterrent materials. State funding was also expected to help the county purchase a curtain burner, but that plan fell through.

Earlier this month, state legislators threatened to cut invasive species funding from the newly expanded Hawai‘i Department of Agriculture and Biosecurity over its slow progress in curbing threats such as coconut rhinoceros beetles.

“I’d like to see the pressure put on them to release the funds to the counties,” Holland said.

by Noelle Fujii-Oride, Honolulu Civil Beat | Read more:
Image: Kevin Fujii/David Croxford/Civil Beat
[ed. Tough, ugly, able to leap sleeping bureaucrats in a single bound. See also: As Palm-Killing Beetles Spread On Big Island, State Action Is Slow (CB):]

***

It has been nearly two years since the first rhinoceros coconut beetle was discovered on Hawaiʻi island. And yet, despite ongoing concern by residents, the state is moving slowly in devising its response.

Seven months ago, the state’s Department of Agriculture and Biosecurity said it would begin working to stop the spread of CRB, within and beyond North Kona. But a meeting of the agency’s board Tuesday marked the first concrete step to do so by regulators. Now, as agriculture department staff move to streamline and resolve apparent issues in the proposed regulations, it will likely take until March for the board to consider implementing them.

Many of the attendees at Tuesday’s meeting, including residents of other islands, said that the state is lagging on its pledge to regulate the movement of agricultural materials while the destructive pest is spreading and killing both the island’s coconut palms and its endangered, endemic loulu palms.

The First Two Years

Before making landfall on Hawaiʻi island in 2023, the beetles spent almost a decade in apparent confinement on Oʻahu.

At first they appeared to be isolated to Waikoloa. Then, in March of last year, larvae and beetles were discovered at Kona International Airport and the state-owned, 179-acre Keāhole Agriculture Park, before spreading further.

In response, the county implemented a voluntary order to discourage the movement of potentially-infested live plants, mulch and green waste, and other landscaping materials such as compost from the area in June 2025. The order was described as “a precursor to a mandatory compliance structure” to be implemented by the state, according to a press release from the time. (...)

The board spent about an hour considering the petition and hearing testimony. And while many who testified made recommendations about actual protocol that might be put into place, the board merely voted to move forward in the process. So it’s not yet clear whether it will adopt the Big Island petitioner’s proposed rules or create its own.

Why Even the Healthiest People Hit a Wall at Age 70

Are we currently determining how much of aging is lifestyle changes and interventions and how much of it is basically your genetic destiny?

 

[Transcript:] We are constantly being bombarded with health and lifestyle advice at the moment. I feel like I cannot open my social media feeds without seeing adverts for supplements or diet plans or exercise regimes. And I think that this really is a distraction from the big goals of longevity science. This is a really difficult needle to thread when it comes to talking about this stuff because I'm a huge advocate for public health. I think if we could help people eat better, if we could help 'em do more exercise, if we could help 'em quit smoking, this would have enormous effects on our health, on our economies all around the world. But this sort of micro-optimization, these three-hour long health podcasts that people are digesting on a daily basis these days, I think we're really majoring in the minors. We're trying to absolutely eke out every last single thing when it comes to living healthily. And I think the problem is that there are real limits to what we can do with health advice. 

So for example, there was a study that came out recently that was all over my social media feeds. And the headline was that by eating the best possible diet, you can double your chance of aging healthily. But I decided to dig into the results table. The healthiest diet was something called the Alternative Healthy Eating Index or AHEI. And even the people who are sticking most closely to this best diet, according to this study, the top 20% of adherence to the AHEI, only 13.6% of them made it to 70 years old without any chronic diseases. That means that over 85% of the people sticking to the best diet, according to this study, got to the age of 70 with at least something wrong with them. And that shows us that optimizing diet only has so far it can go. 

We're not talking about immortality or living to 120 here. If you wanna be 70 years old and in good enough health to play with your grandkids, I cannot guarantee that you can do that no matter how good your diet is. And that's why we need longevity medicine to help keep people healthier for longer. And actually, I think even this idea of 120, 150-year-old lifespans, you know, immortality even as a word that's often thrown around, I think the main thing we're trying to do is get people to 80, 90 years old in good health. 'cause we already know that most people alive today, when they reach that age, are unfortunately gonna be frail. They're probably gonna be suffering from two or three or four different diseases simultaneously. And what we wanna do is try and keep people healthier for longer. And by doing that, they probably will live longer but kind of as a side effect. 

If you look at photographs of people from the past, they often look older than people in the present day who are the same age. And part of these are these terrible fashion choices that people made in the past. And we can look back and, you know, understand the mistakes they've made with hindsight. But part of that actually is aging biology. I think the fact that people can be different biological ages at the same chronological ages, something that's really quite intuitive. All of us know people who've waltzed into their 60s looking great and, you know, basically as fit as someone in their 40s or 50s. And we know similar people who have also gone into their 60s, but they're looking haggard, they've got multiple different diseases, they're already struggling through life. 

In the last decade, scientists have come up with various measures of what's called biological age as distinct from chronological age. So your chronological age is just how many candles there are on your birthday cake. And obviously, you know, most of us are familiar with that. But the idea of biological age is to look inside your cells, look inside your body, and work out how old you are on a biological level. Now we aren't perfect at doing this yet, but we do have a variety of different measures. We can use blood tests, we can use what are called epigenetic tests, or we can do things that are far more sort of basic and functional, how strong your grip is declines with age. And by comparing the value of something like your grip strength to an average person of a given age, we can assign you a biological age value. And I think the ones that are getting the most buzz at the moment within the scientific community, but also all around the internet, are these epigenetic age tests. 

So the way that this works is that you'll take a blood test or a saliva sample and scientists will measure something about your epigenome. So the genome is your DNA, it's the instruction manual of life. And the epigenome is a layer of chemistry that sits on top of your genome. If you think of your DNA is that instruction manual, then the epigenome is the notes in the margin. It's the little sticky notes that have been stuck on the side and they tell the cell which DNA to use at which particular time. And we know that there are changes to this epigenome as you get older. And so by measuring the changes in the epigenome, you can assign someone a biological age. 

At the moment, these epigene clocks are a really great research tool. They're really deepening our understanding of biological aging in the lab. I think the problem with these tests as applied to individuals is we don't know enough about exactly what they're telling us. We don't know what these individual changes in epigenetic marks mean. We know they're correlated with age, but what we don't know is if they're causally related. And in particular, we don't know if you intervene, if you make a change in your lifestyle, if you start taking a certain supplement and that reduces your biological age. We don't know whether that actually means you're gonna dilate or whether it means you're gonna stay healthier for longer or whether you've done something that's kind of adjacent to that. And so we need to do more research to understand if we can causally impact these epigenetic measures. (...)

Machine learning and artificial intelligence are gonna be hugely, hugely important in understanding the biology of aging. Because the body is such a complicated system that in order to really understand it, we're gonna need these vast computer models to try and decode the data for us. The challenge is that what machine learning can do at the moment is it can identify correlations. So it can identify things that are associated with aging, but it can't necessarily tell us what's causing something else. So for example, in the case of these epigenetic clocks, the parts of the epigenome that change with age have been identified because they correlate. But what we don't know is if you intervene in any one of these individual epigenetic marks, if you move it in the direction of something younger, does that actually make people healthier? And so what we need to do is more experiments where we try and work out if we can intervene in these epigenetic, in these biological clocks, can we make people live healthier for longer? 

Over the last 10 or 15 years, scientists have really started to understand the fundamental underlying biology of the aging process. And they broke this down into 12 what are called hallmarks of aging. One of those hallmarks is the accumulation of senescent cells. Now senescent is just a biological technical term for old. These are cells that accumulate in all of our bodies as the years go by. And scientists have noticed that these cells seem to drive a range of different diseases as we get older. And so the idea was what if we could remove these cells and leave the rest of the cells of the body intact? Could that slow down or even partially reverse the aging process? And scientists identified drugs called it senolytic drugs. 

These are drugs that kill those senescent cells and they tried them out in mice and they do indeed effectively make the mice biologically younger. So if you give mice a course of senolytic drugs, it removes those senescent cells from their body. And firstly, it makes them live a bit longer. That's a good thing if you're slowing down the aging process, the basic thing you want to see. But it's not dragging out that period of frailty at the end of life. It's keeping the mice healthier for longer so they get less cancer, they get less heart disease, they get fewer cataracts. The mice are also less frail. They basically send the mice to a tiny mouse-scale gym in these experiments. And the mice that have been given the drugs, they can run further and faster on the mousey treadmills that they try them out on. 

It also seems to reverse some of the cognitive effects that come along with aging. So if you put an older mouse in a maze, it's often a bit anxious, doesn't really want to explore. Whereas a younger mouse is desperate to, you know, run around and find the cheese or whatever it is mice doing in mazes. And by giving them these senolytic drugs, you can unlock some of that youthful curiosity. And finally, these mice just look great. You do not need to be an expert mouse biologist to see which one has had the pills and which one hasn't. They've got thicker fur. They've got plumper skin. They've got brighter eyes. They've got less fat on their bodies. And what this shows us is that by targeting the fundamental processes of aging, by identifying something like senescent cells that drives a whole range of age-related problems, we can hit much perhaps even all of the aging process with a single treatment. 

Senescent cells are, of course, only one of these 12 hallmarks of aging. And I think in order to both understand and treat the aging process, we're potentially gonna only treatments for many, perhaps even all of those hallmarks. There's never gonna be a single magic pill that can just make you live forever. Aging is much, much more complicated than that. But by understanding this relatively short list of underlying processes, maybe we can come up with 12, 20 different treatments that can have a really big effect on how long we live. 

One of the most exciting ideas in longevity science at the moment is what's called cellular reprogramming. I sometimes describe this as a treatment that has fallen through a wormhole from the future. This is the idea that we can reset the biological clock inside of our cells. And the idea first came about in the mid 2000s because there was a scientist called Shinya Yamanaka who was trying to find out how to turn regular adult body cells all the way back to the very beginning of their biological existence. And Yamanaka and his team were able to identify four genes that you could insert into a cell and turn back that biological clock. 

Now, he was interested in this from the point of view of creating stem cells, a cell that can create any other kind of cell in the body, which we might be able to use for tissue repair in future. But scientists also noticed, as well as turning back the developmental clock on these cells, it also turns back the aging clock, cells that are given these four Yamanaka factors actually are biologically younger than cells that haven't had the treatment. And so what scientists decided to do was insert these Yamanaka factor genes into mice. 

Now if you do this in a naive way, so there's genes active all the time, it's actually very bad news for the mice, unfortunately. because these stem cells, although they're very powerful in terms of what kind of cell they can become, they are useless at being a liver cell or being a heart cell. And so the mice very quickly died of organ failure. But if you activate these genes only transiently, and the way that scientists did it the first time successfully was essentially to activate them at weekends. So they produced these genes in such a way that they could be activated with the drug and they gave the mice the drug for two days of the week, and then gave them five days off so the Yamanaka factors were then suppressed. They found that this was enough to turn back the biological clock in those cells, but without turning back the developmental clock and turn them into these stem cells. And that meant the mice stayed a little bit healthier. We now know that they can live a little bit longer with this treatment too.

Now the real challenge is that this is a gene therapy treatment. It involves delivering four different genes to every single cell in your body. The question is can we, with our puny 2020s biotechnology, make this into a viable treatment, a pill even, that we can actually use in human beings? I really think this idea of cellular reprogramming appeals to a particular tech billionaire sort of mentality. The idea that we can go in and edit the code of life and reprogram our biological age, it's a hugely powerful concept. And if this works, the fact that you can turn back the biological clock all the way to zero, this really is a very, very cool idea. And that's what's led various different billionaires from the Bay Area to invest huge, huge amounts of money in this. 

Altos Labs is the biggest so-called startup in this space. And I wouldn't really call it a startup 'cause it's got funding of $3 billion from amongst other people, Jeff Bezos, the founder of Amazon. Now I'm very excited about this because I think $3 billion is enough to have a good go and see if we can turn this into a viable human treatment. My only concern is that epigenetics is only one of those hallmarks of aging. And so it might be the case that we solve aging inside our individual cells, but we leave other parts of the aging process intact. (...)

Probably the quickest short-term wins in longevity science are going to be repurposed existing drugs. And the reason for this is because we spent many, many years developing these drugs. We understand how they work in humans. We understand a bit about their safety profile. And because these molecules already exist, we've just tried them out in mice, in, you know, various organisms in the lab and found that a subset of them do indeed slow down the aging process. The first trial of a longevity drug that was proposed in humans was for a drug called metformin, which is a pre-existing drug that we prescribe actually for diabetes in this case, and has some indications that it might slow down the aging process in people. (...)

I think one of the ones that's got the most buzz around it at the moment is a drug called rapamycin. This is a drug that's been given for organ transplants. It's sometimes used to coat stents, which these little things that you stick in the arteries around your heart to expand them if you've got a contraction of those arteries that's restricting the blood supply. But we also know from experiments in the lab that can make all kinds of different organisms live longer, everything from single-cell yeast, to worms, to flies, to mice, to marmoset, which are primates. They're very, very evolutionarily close to us as one of the latest results. 

Rapamycin has this really incredible story. It was first isolated in bacteria from a soil sample from Easter Island, which is known as Rapa Nui in the local Polynesians. That's where the drug gets its name. And when it was first isolated, it was discovered to be antifungal. It could stop fungal cells from growing. So that was what we thought we'd use it for initially. But when the scientists started playing around with in the lab, they realized it didn't just stop fungal cells from growing. It also stopped many other kinds of cells as well, things like up to and including human cells. And so the slight disadvantage was that if you used it as an antifungal agent, it would also stop your immune cells from being able to divide, which is obviously be a bit of a sort of counterintuitive way to try and treat a fungal disease. So scientists decided to use it as an immune suppressant. It can stop your immune system from going haywire when you get an organ transplant, for example, and rejecting that new organ. 

It is also developed as an anti-cancer drug. So if it can stop cells dividing or cancer as cells dividing out of control. But the way that rapamycin works is it targets a fundamental central component of cellular metabolism. And we noticed that that seemed to be very, very important in the aging process. And so by tamping it down by less than you would do in a patient where you're trying to suppress their immune system, you can actually rather than stopping the cell dividing entirely, you can make it enter a state where it's much more efficient in its use of resources. It starts this process called autophagy, which is Greek for self-eating, autophagy. And that means it consumes old damaged proteins, and then recycles them into fresh new ones. And that actually is a critical process in slowing down aging, biologically speaking. And in 2009, we found out for the first time that by giving it to mice late in life, you could actually extend their remaining lifespan. They live by 10 or 15% longer. And this was a really incredible result. 

This was the first time a drug had been shown to slow down aging in mammals. And accordingly, scientists have become very, very excited about it. And we've now tried it in loads of different contexts and loads of different animals and loads of different organisms at loads of different times in life. You can even wait until very late in a mouse lifespan to give it rapamycin and you still see most of that same lifespan extension effect. And that's fantastic news potentially for us humans because not all of us, unfortunately, can start taking a drug from birth 'cause most of us were born quite a long time ago. But rapamycin still works even if you give it to mice who are the equivalent of 60 or 70 years old in human terms. And that means that for those of us who are already aged a little bit, Rapamycin could still help us potentially. And there are already biohackers out there trying this out for themselves, hopefully with the help of a doctor to make sure that they're doing everything as safely as possible to try and extend their healthy life. And so the question is: should we do a human trial of rapamycin to find out if it can slow down the aging process in people as well? (...)

We've already got dozens of ideas in the lab for ways to slow down, maybe even reverse the age of things like mice and cells in a dish. And that means we've got a lot of shots on goal. I think it'll be wildly unlucky if none of the things that slow down aging in the lab actually translate to human beings. That doesn't mean that most of them will work, probably most of them won't, but we only need one or two of them to succeed and really make a big difference. And I think a great example of this is GLP-1 drugs, the ozempics, the things that are allowing people to suddenly lose a huge amount of weight. We've been looking for decades for these weight loss drugs, and now we finally found them. It's shown that these breakthroughs are possible, they can come out of left field. And all we need to do in some cases is a human trial to find out if these drugs actually work in people. 

And what that means is that, you know, the average person on planet earth is under the age of 40. They've probably got 40 or 50 years of life expectancy left depending on the country that they live in. And that's an awful lot of time for science to happen. And if then in the next 5 or 10 years, we do put funding toward these human trials, we might have those first longevity drugs that might make you live one or two or five years longer. And that gives scientists even more time to develop the next treatment. And if we think about some more advanced treatments, not just drugs, things like stem cell therapy or gene therapy, those things can sound pretty sci-fi. But actually, we know that these things are already being deployed in hospitals and clinics around the world. They're being deployed for specific serious diseases, for example, where we know that a single gene can be a problem and we can go in and fix that gene and give a child a much better chance at a long, healthy life. 

But as we learn how these technologies work in the context of these serious diseases, we're gonna learn how to make them effective. And most importantly, we're gonna learn how to make them safe. And so we could imagine doing longevity gene edits in human beings, perhaps not in the next five years, but I think it'll be foolish to bet against it happening in the next 20 years, for example. 

by Andrew Steele, The Big Think |  Read more:

Image: Yamanka factors via:

[ed. See also: Researchers Are Using A.I. to Decode the Human Genome (NYT).]

Leonardo’s Wood Charring Method Predates Japanese Practice

Yakisugi is a Japanese architectural technique for charring the surface of wood. It has become quite popular in bioarchitecture because the carbonized layer protects the wood from water, fire, insects, and fungi, thereby prolonging the lifespan of the wood. Yakisugi techniques were first codified in written form in the 17th and 18th centuries. But it seems Italian Renaissance polymath Leonardo da Vinci wrote about the protective benefits of charring wood surfaces more than 100 years earlier, according to a paper published in Zenodo, an open repository for EU funded research.

Check the notes

As previously reported, Leonardo produced more than 13,000 pages in his notebooks (later gathered into codices), less than a third of which have survived. The notebooks contain all manner of inventions that foreshadow future technologies: flying machines, bicycles, cranes, missiles, machine guns, an “unsinkable” double-hulled ship, dredges for clearing harbors and canals, and floating footwear akin to snowshoes to enable a person to walk on water. Leonardo foresaw the possibility of constructing a telescope in his Codex Atlanticus (1490)—he wrote of “making glasses to see the moon enlarged” a century before the instrument’s invention.

In 2003, Alessandro Vezzosi, director of Italy’s Museo Ideale, came across some recipes for mysterious mixtures while flipping through Leonardo’s notes. Vezzosi experimented with the recipes, resulting in a mixture that would harden into a material eerily akin to Bakelite, a synthetic plastic widely used in the early 1900s. So Leonardo may well have invented the first manmade plastic.

The notebooks also contain Leonardo’s detailed notes on his extensive anatomical studies. Most notably, his drawings and descriptions of the human heart captured how heart valves can control blood flow 150 years before William Harvey worked out the basics of the human circulatory system. (In 2005, a British heart surgeon named Francis Wells pioneered a new procedure to repair damaged hearts based on Leonardo’s heart valve sketches and subsequently wrote the book The Heart of Leonardo.)

In 2023, Caltech researchers made another discovery: lurking in the margins of Leonardo’s Codex Arundel were several small sketches of triangles, their geometry seemingly determined by grains of sand poured out from a jar. The little triangles were his attempt to draw a link between gravity and acceleration—well before Isaac Newton came up with his laws of motion. By modern calculations, Leonardo’s model produced a value for the gravitational constant (G) to around 97 percent accuracy. And Leonardo did all this without a means of accurate timekeeping and without the benefit of calculus. The Caltech team was even able to re-create a modern version of the experiment.

“Burnt Japanese cedar”

Annalisa Di Maria, a Leonardo expert with the UNESCO Club of Florence, collaborated with molecular biologist and sculptor Andrea da Montefeltro and art historian Lucica Bianchi on this latest study, which concerns the Codex Madrid II. They had noticed one nearly imperceptible phrase in particular on folio 87r concerning wood preservation: “They will be better preserved if stripped of bark and burned on the surface than in any other way,” Leonardo wrote.

“This is not folklore,” the authors noted. “It is a technical intuition that precedes cultural codification.” Leonardo was interested in the structural properties of materials like wood, stone, and metal, as both an artist and an engineer, and would have noticed from firsthand experience that raw wood with its bark intact retained moisture and decayed more quickly. Furthermore, Leonardo’s observation coincides with what the authors describe as a “crucial moment for European material culture,” when “woodworking was receiving renewed attention in artistic workshops and civil engineering studies.”

Leonardo did not confine his woody observations to just that one line. The Codex includes discussions of how different species of wood conferred different useful properties: oak and chestnut for strength, ash and linden for flexibility, and alder and willow for underwater construction. Leonardo also noted that chestnut and beech were ideal as structural reinforcements, while maple and linden worked well for constructing musical instruments given their good acoustic properties. He even noted a natural method for seasoning logs: leaving them “above the roots” for better sap drainage.

The Codex Madrid II dates to 1503-1505, over a century before the earliest known written codifications of yakisugi, although it is probable that the method was used a bit before then. Per Di Maria et al., there is no evidence of any direct contact between Renaissance European culture and Japanese architectural practices, so this seems to be a case of “convergent invention.”

The benefits of this method of wood preservation have since been well documented by science, although the effectiveness is dependent on a variety of factors, including wood species and environmental conditions. The fire’s heat seals the pores of the wood so it absorbs less water—a natural means of waterproofing. The charred surface serves as natural insulation for fire resistance. And stripping the bark removes nutrients that attract insects and fungi, a natural form of biological protection.

by Jennifer Ouellette, Ars Technica |  Read more:
Images: A. Di maria et al., 2025; Unimoi/CC BY-SA 4.0; and Lorna Satchell/CC BY 4.0