The journal Science has published a map of aging of 40 human hippocampi: with age, microglia, astrocytes, and DNA layout change. On July 23, a peer-reviewed article by Nathan Sestan's team was published in Science. The authors studied post-mortem tissues of 40 people from 20 to 100 years old and simultaneously examined gene function, chemical DNA marks, and how chromosomes fold inside the cell nucleus. The hippocampus helps to remember events and navigate in space. Usually, age-related changes in the brain are discussed as a single general indicator, but the authors divided the material by cell type. They found that aging affects both the composition of cells and the way these cells manage genes. In samples of people 50-75 years old, the proportion of embryonically derived microglia decreased. Microglia are immune cells of the brain: they clean up cellular debris, respond to damage, and participate in tuning nerve connections. At the same time, cells with a profile similar to microglia from peripheral blood monocytes became more noticeable. There were also fewer astrocytes, which support signal transmission in synapses. This result is consistent with the SuperAgers map: in people over 80 years old with preserved memory, support programs were highlighted in astrocytes and CA1 neurons. The new work looks at the same cellular environment across the age scale and records a decrease in the proportion of astrocytes in the hippocampus. The most unusual observation concerns the three-dimensional layout of DNA. The chromosome in the nucleus is not stretched into a straight thread: distant DNA segments can be located nearby and together influence gene function. In many cell types, this spatial organization blurred with age. The authors' open version also describes the transition of microglia from a calm state to a state prepared for inflammation. In one human sample, the authors linked age-related changes in microglia and astrocytes with the rearrangement of gene regulation and DNA layout. The map shows the aging of the hippocampus as a set of specific cellular shifts, rather than as a single indicator for the entire brain.

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A 67% reduction in valine extended the lifespan of male mice by 23%. On July 24, a study on the lifelong diet of C57BL/6J mice was published in Nature Aging. Researchers reduced only valine in the diet, preserving calorie, fat, and carbohydrate content; median lifespan increased in males, and several health indicators improved in both sexes. Valine is an essential amino acid obtained from food, part of the BCAA group along with leucine and isoleucine. The Nature Aging article reported that the C57BL/6J mouse diet, starting at four weeks of age, contained 67% less valine; the deficient amount was replaced with amino acids that the body can synthesize itself. This single shift changed several indicators: mice of both sexes gained less fat, better controlled glucose, and received lower frailty index scores - a set of tests for age-related disorders. Median lifespan increased by 23% in males. In females, health indicators improved, but lifespan did not change. The authors measured different tissue responses: mice with valine restriction consumed more calories per unit of body mass and expended more energy at 18 months. In males, mitochondrial respiration intensified in the liver: mitochondria more actively converted food energy into molecules that cells use to fuel their work. In females, the proportion of neuroinflammatory glial cells - cells that support neuron function - decreased more strongly. A 2021 experiment with lifelong restriction of all three BCAAs extended the lifespan of male mice by approximately 30%. The new study separates valine from leucine and isoleucine: a single change in the diet was enough to improve health indicators in both sexes and extend the lifespan of males. This allows researchers to compare the response of individual tissues to each amino acid, rather than reducing all proteins at once.

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AcroCyte announced funding for ARPA-H kidney organoid growth technology from patient cells on July 23. AcroCyte Therapeutics reported that ARPA-H is supporting its R3CE technology. The company grows small three-dimensional tissue fragments - kidney organoid modules - from a patient's kidney cells. The company describes R3CE as a method for multiplying rare human cells in three-dimensional culture. In a July 23 release, AcroCyte writes that kidney cells are obtained through a minimally invasive procedure, expanded in culture over weeks, and grown into organoid modules. The company is attempting to make the transition from a small cell sample to organoid material repeatable. The organoid has several engineering challenges. Two weeks ago, a USC team showed how the WNT signal gives nephrons in a kidney organoid direction for growth. AcroCyte's application relates to a different stage: obtaining the cellular material from which tissue modules are then grown. AcroCyte also named project partners: University of Chicago Medicine, National Taiwan University Hospital, and the National Center for Biomodels. According to the release, they will work in the US and Taiwan. ARPA-H support is focused on R3CE - a technology that should provide comparable batches of cells for growing organoids. ARPA-H funds risky medical technologies and solutions that can be scaled up. For AcroCyte, scaling begins with reproducible growth of rare cells: it depends on whether the same growth method can provide comparable tissue modules.

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Scribe has set the price for its IPO: 8.58 million shares at $15 for the development of CRISPR programs. On July 23, Scribe set the price for its increased IPO: 8.58 million shares at $15. The company estimates gross proceeds, before expenses, to be $128.7 million; trading of SCTX on Nasdaq and the deal closure are scheduled for July 24 and 27. Scribe's main program is already undergoing its first human trial. Scribe Therapeutics has set the price for its increased IPO: 8.58 million common shares at $15. The company expects gross proceeds of $128.7 million, before expenses related to the offering; the deal closure is scheduled for July 27, subject to customary conditions. In Scribe's preliminary filing on July 2, the price and volume had not yet been specified. In its S-1 filing, the company indicated that it plans to use the net proceeds, together with its existing funds, for STX-1150, two other programs, and ELXR/XE technologies. STX-1150 is being developed for the long-term reduction of LDL-C, "bad" cholesterol. The liver produces the PCSK9 protein; it removes receptors that capture LDL-C from the blood from the cell surface. If PCSK9 is suppressed, more receptors remain, and they remove more LDL-C. STX-1150 is delivered to the liver in lipid nanoparticles, i.e., fatty shells for the drug payload. The ELXR system places chemical marks on the PCSK9 gene and reduces its activity without changing the DNA sequence. Thus, Scribe is trying to suppress PCSK9 for a long time by regulating gene function. The company's prospectus describes the first trial in Australia: it may include up to 64 adults with elevated LDL-C and a risk of atherosclerotic cardiovascular disease. In the first half of 2027, Scribe expects to receive data on safety, tolerability, and LDL-C reduction. The prototype in a non-human primate experiment showed that a single dose maintained a reduction in LDL-C of more than 50% for two years. BioPharma Dive calls Scribe the first gene-editing drug developer to go public in more than two years. The set price ties the development of the clinical STX-1150 program and early CRISPR programs to the public offering, which the company plans to close on July 27.

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On July 13, the Sakana AI, IT University of Copenhagen, and Autodesk Research team published an experiment in Nature Communications with four assemblies of 26–197 identical modules. A plane, guitar, boat, and round table in all three repeats came to the correct answer about their shape in 23 cycles, approximately 70 seconds. Each module is a printed circuit board in a cube enclosure. A microcontroller runs the same small neural network, an LED displays its current answer, and connectors on six faces transmit messages to neighbors. The cube has no coordinates and no overall map of the assembly: it knows only its internal state and what the attached cubes send it. The authors trained a neural cellular automaton — a network where each cube applies the same update rule. The cube changes its internal state, receives new messages from neighbors, and counts again. Signals spread through the assembly until different parts come to one label: plane, guitar, boat, or table. The network first learned in simulation on seven classes of objects, and then the same rule was transferred to physical modules. In its hidden channels, the authors saw stable spatial gradients: the state of the cube changed depending on its place in the assembly. Such a signal gives the cube a relative landmark, although no one reports coordinates to it. In simulation, the authors assigned the network another task: to simultaneously name the shape and indicate one of the six directions to a missing cube. The network found the direction with an average accuracy of 94.8%, while maintaining 98.9% accuracy of shape recognition. Then the program added a virtual cube in the indicated direction and repeated the calculation. An assembly that needs to find a place of failure must first agree on what object it forms. The team demonstrated this computational step on almost two hundred cubes connected only with nearest neighbors.

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A map of 86,000 cell nuclei from 16 tissues linked DNA layout to methylation. On July 23, a study on 86,689 human cell nuclei was published in Science. The authors simultaneously measured DNA methylation and three-dimensional chromatin contacts in each nucleus - how the long DNA molecule folds and which parts of it end up nearby. Nerve, muscle, and immune cells have almost the same DNA sequence. Different roles are assigned to them by chemical marks on DNA and its layout in the nucleus: methylation marks individual sites, and spatial contacts can bring a regulatory site closer to a gene. Previous maps usually measured these two layers separately or in separate organs. Here, they were read in the same nuclei across 16 tissues. Two measurements in one nucleus allow distinguishing a stable cell type from a transitional state. In skeletal muscle, the authors found fibers whose three-dimensional layout already resembles mature muscle, while methylation retains signs of a muscle stem cell. The GEN breakdown links this discrepancy to the different update rates of the two epigenetic layers. One cell can look mature in terms of DNA layout and retain a trace of its previous state in methylation. The same map helps link a risk variant to the cell in which it can change gene function. Many variants associated with diseases lie in non-coding DNA regions: they do not create protein, but can regulate gene activity. By linear sequence, it is difficult to understand which gene such a region affects. Three-dimensional contacts show possible connections, and methylation indicates the cell type. When comparing known risk variants to the atlas, variants associated with atrial fibrillation fell on heart muscle cells, and variants of bipolar disorder and schizophrenia - on excitatory and inhibitory neurons. Thus, researchers obtain specific cellular hypotheses for experiments on disease mechanisms.

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Tomorrow Bio has launched Pets of Tomorrow, a pre-arrangement program for animal cryopreservation. On July 22, the company introduced a service where pet owners can pre-fill out their personal file, sign a contract, and choose a payment method. For vitrification, the animal must arrive at Ralfc within ten hours of being cooled to 4 °C. After a pet's death, the family must simultaneously arrange for transportation, pay for the procedure, and meet a short time window. Tomorrow Bio's Pets of Tomorrow page allows owners to do this in advance: fill out their personal file, receive a contract with a digital signature, choose financing and storage route. The service shifts organizational decisions to when the animal is still alive. This is the change compared to the previous cryopreservation service: the contract, payment, and logistics are gathered into a public procedure, rather than remaining a subject of urgent correspondence after the pet's death. The company calls the fee a lifetime membership costing €500 and credits it towards the procedure price. Preservation costs range from €30,000 to €150,000: the price depends on the species, size of the animal, and chosen option. Payment can be made by bank transfer, card, cryptocurrency, or monthly in Switzerland. Tomorrow Bio states that it stores animals in Ralfc at a temperature of liquid nitrogen, around −196 °C. There are two options: standard cryopreservation and vitrification. With vitrification, tissues are treated with cryoprotectants and rapidly cooled to reduce ice formation. For this option, the route to Ralfc is limited to ten hours. The standard option gives transportation more time. A pre-arranged case leaves only one practical step after death: to initiate the chosen transportation and procedure.

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On July 21, an article about the Generative Cognitive Map Learner, or GCML, was published in Nature Machine Intelligence. The authors tested this computational model on graphs and in a task where a silhouette needs to be broken down into blocks. To create a plan, the system first needs to learn the environment. It takes a step to the right and sees a new position; removes a block and gets a different figure. When a goal appears, the model iterates through the next steps, relying on this experience. GCML binds observations and actions into one map. It learns which action usually translates the system from one state to a neighboring one. Having received a goal, the model matches it with the current state, selects an imaginary next step, predicts a new state, and repeats this cycle. Thus, the model takes on a new goal without re-exploring all branches. Randomness in step selection gives not one route, but several. With weak noise, most paths on the graph have a minimal length; with stronger noise, different options appear, but their lengths remain close to minimal. From these, you can choose a path based on an additional condition, such as a reward at intermediate points. On random graphs and in the task with silhouettes, the authors checked whether the model transfers the learned knowledge to new combinations. GCML learned to break down silhouettes into five blocks, and then built a sequence of block removals for new silhouettes from eight. On graphs, it suggests paths close to the shortest, but not guaranteed to be optimal. The biological motivation for this design is specific. In rat hippocampus recordings, short sequences of place cells corresponded to future paths to a remembered goal. The authors suggest such a mechanism for this "playing forward": experience of steps forms a map, and the map generates trajectories to the goal. In simulation, the model reproduces the qualitative properties of these trajectories. For AI that works with experiments, the principle can be formulated as follows: first, collect transitions "action - measured result", and then, based on this map, suggest several next experiments instead of a complete re-exploration of combinations. The plan here arises from accumulated experience of actions, rather than from a new search from scratch.

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On July 1, in Nature Biotechnology, a team led by Sami Nurreddin published a study in which they mapped the consequences of suppressing 11,692 genes in human iPSCs: in the KOLF2.1J human iPSC line, scientists suppressed 11,692 expressed genes and read RNA from more than 2.5 million individual cells. The browser atlas, processed data, and code are open access. Induced pluripotent stem cells are derived from adult cells and returned to a state from which different tissue types can be grown. Researchers who want to derive cells from them for therapy need to maintain iPSCs in this state and guide them towards the desired tissue. The RNA activity map shows which genes work together in an already formed cell. The authors of the article intervened in this process. CRISPRi uses a guide RNA: it brings the dCas9 protein with a repressive domain to the chosen gene, which reduces gene reading. In a common culture, each cell receives its own guide, and single-cell RNA sequencing records how the work of the remaining genes changes after intervention. The atlas links the suppression of each gene to the measured cell response. When the suppression of two genes leaves a similar trace in RNA, researchers obtain candidates for separate verification of a common cellular function. In this work, the authors checked the role of ZBTB41 in cellular metabolism, RNF7 in maintaining pluripotency, and DBR1 in RNA editing, where adenosine is converted to inosine. Now the next experiment can start with a gene and an observed cell response. In the open browser atlas, other groups can search for such responses, compare iPSC lines, and reprogramming variants. The processed data and code give them material to test genetic interventions when creating and controlling cells that replace damaged tissues.

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The protein CTCF at nuclear speckles changes RNA processing in aging cells. On July 21, Spiros Paliouras and his colleagues published an article on how human cells establish senescence - a stable cessation of division. In cell cultures, clusters of the CTCF protein assembled near nuclear speckles; their disruption altered the set of RNAs and delayed the cessation of division. A senescent cell stops dividing, but continues to change gene function. One gene can give several versions of messenger RNA - instructions for assembling a protein. Splicing cuts and connects sections of the original RNA, determining which version is produced. A senescent cell has its own stable set of such versions. The nucleus has nuclear speckles - areas where RNAs and proteins involved in splicing assemble. CTCF helps DNA fold into loops and separates neighboring chromosome regions. The authors found that upon entering senescence, CTCF forms clusters near speckles. The experiments were conducted on human lung fibroblasts IMR90; the researchers compared chemically induced senescence with cells that had aged after normal divisions. Previously, this same line of work had linked the onset of senescence to the departure of the HMGB2 protein from the nucleus and the clustering of CTCF. The new work adds BANF1, which is involved in chromosome organization, and SRRM2 - a component of nuclear speckles - to this chain. In a cellular model, the loss of HMGB2 changes DNA layout; CTCF and BANF1 reorganize it near speckles, and SRRM2 links this reorganization to RNA processing. When the researchers disrupted CTCF clusters, the characteristic senescent set of RNA variants almost returned to the state of dividing cells, and the cells stopped dividing later. In skin fibroblasts from donors of different ages and in whole blood data, the authors also saw age-related changes in this program.

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Brian Johnson is shifting Immortals from telemedicine to cellular models and personal therapies. On July 24, Johnson reported that two weeks earlier, he had changed the focus of his longevity company. Immortals retains its current medical services and adds work with an individual's cells to seek out therapeutic hypotheses for them. In a July 24 post, Johnson wrote that he had focused Immortals on creating an infrastructure that would allow people to explore and solve their own health problems. He and Kate named themselves as the first clients: both are dealing with recent diagnoses. "Two weeks ago, I focused my company Immortals on creating an infrastructure that would allow people to find and fix their own health problems. We are adding induced pluripotent stem cells, organoids, deep cell characterization, and the development of personal therapies." Currently, Immortals sells prescription assignments, biomarker tests, telemedicine, and doctor accompaniment. In June, Immortals Medicine formalized this set into a service with a questionnaire, a doctor, a pharmacy, and delivery. Now, Johnson wants to add cellular models of the client themselves to the analysis and data from wearable devices. Induced pluripotent stem cells are obtained from adult cells and returned to a state from which different tissue types are grown. An organoid is a three-dimensional cell culture that reproduces a part of a tissue device. A review of brain organoids describes how such cultures preserve the genetic background of the donor: they are used to study disease manifestations in human cells and test drug candidates. The declared Immortals chain looks like this: a person's data and diagnosis give rise to a question, their cells help gather a model, and then a suitable therapy is sought on it. Johnson is adding research work with individual biomaterial to consumer medicine.

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Victor Dzau has joined the board of United Therapeutics, which develops organs for transplantation and their substitutes. On July 23, United Therapeutics announced that on July 22, it had appointed physician and researcher Victor Dzau to its board of directors. Dzau had completed 12 years as the head of the US National Academy of Medicine, returned to Duke University, and joined a company seeking ways to increase the number of organs available for transplantation. A patient with terminal organ failure needs a compatible organ, but there is a shortage of donor organs. United Therapeutics claims to be developing transplantable organs and their substitutes for such patients. In early July, it acquired Thymmune, which is developing thymus cells. The thymus is involved in the immune system, so this deal relates to one of the problems of transplantation: the body may reject the new organ. The path from laboratory development to transplantation goes through the clinic and hospital, and it is this path that Dzau's biography helps to illuminate. He studied cardiovascular diseases, managed hospital systems and medical departments of universities. Dzau headed the healthcare system at Duke University, the medical departments at Harvard and Stanford, and then spent twelve years as the president of the US National Academy of Medicine. His early work helped create ACE inhibitors, which are used to treat hypertension and heart failure; he is now researching heart regeneration. In the announcement of his appointment, Dzau explained why he joined the board: "I am pleased to join the board and look forward to supporting United Therapeutics in developing treatments for rare diseases and bio-medical and bio-engineering solutions that should help overcome the serious shortage of organs for transplantation." United Therapeutics has added a physician to its board who has worked with research, hospitals, and medical institutions. For a company building organ substitutes, this experience relates to the same route that the technology must take to reach the patient.

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After the death of a 27-year-old patient in the Bronx, the owner of a wellness center was charged on July 19. Elizabeth Baron had come to the Bereshit Lifestyle Center on Riverdale Avenue in the Bronx for a procedure that police described as a rejuvenating injection. She became ill during the procedure and was pronounced dead at NewYork-Presbyterian Allen Hospital. On July 20, ABC7 reported that the center's owner, Luis Rohas Cabrer, had been charged with reckless endangerment and unauthorized practice of a profession. According to authorities, he has a license in the Dominican Republic but not in the US. Under the guise of rejuvenation, a patient buys one service, although several different solutions are behind it. This substance, its production and quality control, dose preparation, method of administration, and the person monitoring the patient are all part of the process. For the person on the couch, these links merge into one IV drip or injection. Lifespan writes that Baron received an intravenous procedure with NAD⁺, a coenzyme involved in cellular energy metabolism and DNA repair. NAD⁺ is sold to the longevity market in supplements, nasal sprays, and IV drips. The simple promise to "boost NAD⁺ levels" easily obscures the fact that intravenous administration remains a medical procedure. Aging researcher Matt Kaeberlein, in conversation with Lifespan, listed possible sources of risk: the biology of the intervention, production and quality control, preparation and administration. He separately named unlicensed practitioners and unregulated channels as hazards. The name of the procedure does not answer the patient's main question: who is administering the drug, how was it prepared, and who is responsible for safety.

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In Navarre, 60 people aged 100 and over will be divided between a usual routine and 12 weeks of home exercises. On July 23, the BIOANCIENT_EX record appeared on ClinicalTrials.gov. The team will compare the physical function of participants before the program and after 12 weeks, when one group maintains their usual routine and the other exercises at home. When a centenarian walks and gets up better, observation alone does not separate the effect of movement from initial health: a stronger person more often preserves both function and the ability to train. BIOANCIENT_EX will test this by comparing two groups created by random distribution before the start of training. This will allow researchers to compare changes in physical function with the usual routine of participants. The trial plans to include 60 residents of Navarre who are 100 years old and can stand up and sit down on their own or with minimal assistance. One group will maintain their usual routine. The other will perform strength exercises, static and dynamic balance exercises, joint mobility, flexibility, and aerobic exercise at home. The team changes the complexity every three weeks, communicates with participants by phone or video, and visits them at home if necessary. The main measurement will be the SPPB - a physical function scale from 0 to 12 points. Participants will hold balance, walk a short distance, and stand up from a chair several times; the results of these tasks will be added up into one score. After 12 weeks, researchers will also compare hand and leg strength, autonomy in daily life, mobility, cognitive tests, and RNA profiles in plasma and extracellular vesicles. In a 2025 Spanish study, 12 participants completed 12 weeks of strength training in a nursing home: six trained under supervision, six formed a control group. In the training group, the median SPPB score increased from 2.3 to 5.0. BIOANCIENT_EX transfers the training to the home, plans to recruit 60 participants, and adds balance, flexibility, and aerobic exercise. The protocol will test the change in function in centenarians in this format of training.

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A neural network has restored an electrical model of a heart cell from a single recording. On July 23, a study was published in eLife on heart cells grown from reprogrammed stem cells. The authors recorded the response of two living cells to a specially calculated sequence of voltages and assembled a computational model from each recording. A cardiomyocyte contracts after an electrical impulse, which is created by ion channels in the membrane: some allow sodium and calcium to enter the cell, while others release potassium and return the voltage to its initial level. A typical recording shows the overall result of their work. To explain the shape of the impulse, a researcher needs the individual properties of each current. In the eLife article, the team of Pei-Chi Yang first created 1.1 million synthetic models of cardiomyocytes, modifying 52 parameters of six ionic currents and calculating how the cell would respond to different voltage commands. From this population, the authors selected a voltage clamp protocol: a device that holds a specified voltage on the membrane and measures the current in response to each command. The neural network was trained on synthetic recordings to find the parameters that generated them. Then, it was given a recording of a living cell and obtained a set of parameters for its model. From a single electrical recording, the authors determined the properties of the six ionic currents of a separate cell. In their calculations, such a model reproduced the measured electrical impulse of the cell. The authors tested this approach on two cardiomyocytes of one iPSC line, which are cells obtained by reprogramming an adult cell into a stem cell and then growing it towards heart muscle. Using the restored models, the team calculated the movement of calcium inside the cell, which triggers its contraction. The idea of modeling differences between heart cells emerged earlier. In a 2013 PNAS study, researchers matched a population of models to experiments on rabbit Purkinje fibers and compared predictions with responses to four concentrations of dofetilide. The new study automates the reverse path: from a single recording of a human iPSC cell to the parameters of its model. The authors obtain a cycle in which the cell measurement sets the model, and the model formulates a question for the next experiment. The parameters of the six currents turn the shape of the electrical impulse into a testable hypothesis about the cell's mechanism of action.

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On July 24, Norn Group and Effy Klimi published an essay "Sisyphus, MD" on the design of clinical trials. The authors write: an intervention may be calculated to affect several age-related diseases, but in a clinic, it is usually tested against one diagnosis. According to the authors' logic, a therapy that is supposed to affect several aging processes comes to the clinic through a specific disease: heart failure, Alzheimer's disease, or diabetes. The company recruits patients with this diagnosis, pre-selects a measurable outcome, and compares the treatment with standard care. A narrow group provides a clearer signal of benefit and risk, which is easier to discuss with regulators, doctors, and investors. Thus, the method of testing narrows the task of the drug to one diagnosis in advance. After the first approval, the term of market exclusivity limits the incentive to pay for trials for other diseases: they again require money, patients, and time. Therefore, a therapy designed for the general course of aging takes the form of a medicine for one disease. The authors suggest testing the treatment for two other outcomes. The first is to track the time until the first age-related disease. The second is to see if a person maintains mobility, avoids age-related frailty, and preserves their "internal potential": a combination of physical and mental abilities. Such a trial could measure not one diagnosis, but functional decline and several age-related risks. For such trials, methods are needed to reliably measure these outcomes. The ARPA-H PROSPR program is developing biochemical and physiological markers, home data collection, and protocols that should allow evaluating age-related outcomes over three years. In the Norn Group essay, this work is an example of infrastructure without which broad hypotheses about aging are difficult to test in humans.

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A White House report proposes infrastructure for mapping brain connections; neurobiologists debate whether it will crowd out fundamental science. On July 21, the White House Office of Science and Technology Policy released a report titled "Science: A New Golden Age". On July 24, The Transmitter gathered the reaction of neurobiologists to one of its examples: the Connectome, a map of contacts between neurons. In the OSTP report, its mapping is cited as a possible task for X-Lab, a National Science Foundation program that funds independent research organizations outside the traditional academic environment. Such teams receive operational autonomy and money based on achieved milestones. The document proposes a hypothetical mission: academia, industry, and philanthropists could together scale up maps of connections in several species of small mammals. It suggests starting with chains related to reward and motivation. The authors compare the desired effect to the Human Genome Project, after which sequencing became a routine service. Maps of such chains could help study depression, addiction, and autism. The debate is about who will be able to do science before the emergence of large infrastructure. Neurobiologist Jason Shepard fears that with a finite federal budget, large programs will narrow the space for research that laboratories choose out of curiosity. Jeff Lichtman, one of the pioneers of connectome visualization, notes that the methods of this field grew in universities, not from industrial demand. Jan Vesel supports long-term funding of missions, but according to him, a lot of fundamental work is still needed for the application of neuroscience in medicine. Former director of the National Institute of Mental Health Thomas Insel formulates the dilemma more simply: the country needs both industrial teams and university science. Otherwise, the future common machine may not have the ideas that it is supposed to scale.

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Frontier Bio has passed the first stage of the NIH competition with a blood-brain barrier model. On July 21, Frontier Bio announced its victory in the first stage of the NIH Complement-ARIE competition. The company presented NeuroTraX-AI: a human cell-based model of the blood-brain barrier, the state of which an algorithm evaluates from ordinary microscopic images. The victory brought a cash prize and advanced the company to the next stages of the competition with a total fund of $7 million. For a brain drug, it's not enough to just get into the bloodstream. It needs to pass through the blood-brain barrier - a layer of cells in the walls of brain vessels. It protects the brain, allowing some substances to pass through and retaining others. Therefore, it's crucial for developers to understand before human trials whether the candidate will reach brain tissue and damage the vascular protection. Frontier Bio grows a human cell model of the neurovascular unit: a fragment of the environment around a brain vessel. An ordinary microscope captures cells without stains, and NeuroTraX-AI quantitatively evaluates the state of the barrier from these images. According to the company's description, the system shows whether the barrier retains its properties, whether intervention disrupts them, and whether the test agent passes through it. The image of the cell culture becomes a measurement of the barrier's state. Instead of manual viewing of images, the developer receives an indicator for early verification of the candidate on a human cell system. This verification answers a practical question: how a substance behaves at the border between blood and brain. The Complement-ARIE competition supports laboratory and computational methods that can replace part of animal testing. The first stage selected a pair of a human barrier model and automatic analysis of its images. For developers of brain disease treatments, this is a way to earlier determine which candidates are worth moving to the next verification stage.

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On July 24, an article about UniPert-G2CP was published in Cell. The model teaches how a molecule changes the state of a cell by linking the results of genetic experiments with cell reactions to small molecules - chemical compounds that are often the starting point for drug discovery. A cell does not respond to a drug with a single button: a molecule binds to a target protein and then changes the work of many genes. The same drug can cause different reactions in different types of cells. Therefore, a chemical screen requires multiple separate experiments: for each molecule, researchers treat cells and measure which RNAs have changed in them. A genetic screen provides such a map of states much more widely. In a common variant, CRISPR turns off a single gene, after which researchers take a profile of the cell's RNA. The map shows what state the intervention in each gene causes. In May, TxPert predicted the transcriptomic response to new genetic interventions; UniPert-G2CP links such maps to the structure of small molecules. The Connectivity Map in the LINCS program is already collecting profiles of genetic interventions and compounds. These can be used to match the traces that genes and drugs leave in cells. UniPert-G2CP uses this map for chemical search. The model receives a target protein and the structure of a molecule, translates them into a common representation, and matches them with the measured cell profile. Genetic experiments show how a cell responds to the shutdown of a specific gene; chemical experiments link similar profiles to real molecules. The authors checked the transfer on LINCS data: 4,994 genes and 7,860 molecules in five cancer cell lines. When one-fifth of the chemical measurements were left for training, pre-training on genetic screens increased the average correlation of the predicted and measured transcriptome by 375.4%. This figure describes the coincidence of two RNA profiles, not the number of drugs found. To search for substances that change the age-related states of cells, the same sequence is needed: describe the cellular effect of a protein target and select molecules that can cause the desired profile. UniPert-G2CP provides a way to narrow down this selection to laboratory verification of candidates.

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Asimov is creating a system at Boston University to test whether a therapeutic protein can be manufactured. On July 24, Asimov announced that it will design variants of therapeutic proteins on a computer, produce them in the DAMP laboratory at Boston University, and measure the properties of the finished product. These results will be fed back into the model, which will select the next sequence. A therapeutic protein starts with a sequence of amino acids, but that's not the end of the work. It still needs to be produced in cells, purified, and tested. Sometimes, it's at this stage that it becomes clear that a design that was successful on the computer is difficult to turn into a product. In the July 24 announcement, Asimov describes the sequence of actions: the company designs protein variants, the laboratory produces them and measures the manufacturing-related properties, and the model receives the results. The result of each experiment will become data for selecting the next batch of variants. The manufacturability of the protein will thus be taken into account in the decision on its sequence even before the next cycle of experiments. DAMP is the design, automation, manufacturing, and processes laboratory at Boston University. It already performs remotely ordered experiments with biological materials, chemicals, and liquids. Asimov will create a section there for working with therapeutic proteins and will become one of the laboratory's first users. The BU laboratory is part of the Programmable Cloud Laboratory Test Bed network. On July 22, the US National Science Foundation allocated $380 million over four years to the network for 20 laboratory nodes; the Astera Institute adds up to $20 million. BU will receive up to $20 million for its node. The network is expected to allow laboratories to use common methods and experiment results. Asimov is linking protein design to what happens during its actual production. A protein that can be produced and measured provides the model with an example for the next selection; a protein with poor manufacturing properties helps to weed out similar sequences earlier.

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The Verge: Genesis Mission has selected 278 AI projects, and laboratories and universities are to verify their hypotheses. On July 24, The Verge published an analysis of the first projects of the American Genesis Mission - a government AI program for science. Robert Hart links it to the new White House plan and asks if science has enough people and places to test machine proposals. On July 22, the US Department of Energy selected 278 Genesis Mission projects for grant negotiations. Teams from national laboratories, universities, companies, and non-profit organizations will gain access to computational power, models, and programs for research. The White House plan "Science: A New Golden Age," published on July 21, suggests relying on individual researchers, new organizations, and partnerships with companies. The grant provides the team with calculations and models; hypothesis verification remains the work of researchers and laboratories. AI can propose a molecule, material, connection in data, or experiment scheme. A researcher sets up a control experiment, a laboratory obtains a measurement, and another group repeats it on new samples. In The Verge's analysis, physicist Andreas Karth describes the risk: AI will produce many plausible options, and there will be fewer people with experience to filter them. "AI may have several big ideas buried under mountains of useless material, and there will be far fewer people with experience to distinguish one from another." In biomedicine, after laboratory experiments come clinical trials: they determine whether a person's condition changes. Each transition from model to experiment, repetition, and clinic filters out some convincingly sounding hypotheses. The debate about Genesis Mission concerns this entire chain: calculations accelerate the search for options, and universities and laboratories teach people to set up experiments, verify results, and prepare the next generation of researchers.

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