James' World 2

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In the 1600s, fishers in Peru saw that every few years around Christmastime, the waters there warmed, and they caught fewer anchovies. They called this “El Niño” – the boy – after the Christ child.

In the early 20th century, the physicist Gilbert Walker noticed that the prevailing low atmospheric pressure and rainy weather over the western Pacific and dry, high pressure over the eastern Pacific periodically flipped. But it wasn’t until 1969 that meteorologist Jacob Bjerknes linked the two, showing that swells of warm water in the Pacific Ocean end up wreaking havoc on weather across the globe.

Under normal conditions, the sun’s heat and Earth’s spin fuel east-to-west trade winds around the tropics, which blow water into a “warm pool” near Indonesia. As this warm pool grows, it builds up energy. “It could be a bit like a coiled spring waiting to emerge,” says Richard Allan at the University of Reading, UK.

Every two to seven years, natural chaotic disturbances release that spring. Bursts of westerly winds can blow against and slow the easterly trade winds, allowing swells of warm water to roll across the Pacific Ocean, raising sea levels along the coasts of Peru, Colombia and Ecuador. These so-called Kelvin waves indicate that El Niño is coming.

A self-reinforcing cycle called the Bjerknes feedback kicks in. The blob of warm water suppresses the upwelling of cold, nutrient-rich deep water that normally makes Peru’s anchovy fishery so rich, further warming the surface water. The warm sea heats the air above it and causes it to expand. The resulting fall in atmospheric pressure slows the trade winds down even more, since winds flow from high to low pressure. This allows still more warm water to slosh back into the eastern Pacific.

The swathe of warm water stretching across the tropical Pacific releases trillions of joules of heat energy into the atmosphere, raising worldwide temperatures on top of global warming. This is why scientists expect 2027 to be the hottest year on record. But it also drastically alters weather patterns, bringing drought and wildfires to some areas and storms and flooding to others.

Normally, warm air rises over the warm pool, carrying moisture that falls out in thunderstorms, which is why rainforests flourish in places like Indonesia. Denuded of moisture, this warm, dry air then reaches the top of the troposphere and spreads out to the east and west. It descends over the eastern Pacific and the Horn of Africa, fuelling a belt of such air loops around the tropics called the Walker circulation.

During El Niño, however, the warming of the eastern Pacific moves this upward convection eastward, shifting the entire Walker circulation. Now dry, warm air that was sinking over the Horn of Africa and the eastern Pacific is sinking over Indonesia and the Amazon, encouraging drought and wildfires there. Over eastern Africa, warm air is rising, increasing rainfall and the risk of flooding.

Meanwhile, the warming waters also create a stronger temperature contrast between the tropical and northern Pacific, strengthening the jet stream and bringing more storms and wet weather to the southern US. It can bring storms and rain to the UK as well, in certain circumstances.

“If this deep convection in the atmosphere moves around, it changes things locally, but it also then starts to change the whole circulation of the atmosphere,” says Tim Stockdale at the European Centre for Medium-Range Weather Forecasts. “That’s why El Niño is a big deal, not just some local process.”

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Meta and Fourier developed Max in just three months before starting work on its successor, Max 2, in September (representational age).Fourier/YouTube

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Like a lot of Americans, I’ve grown accustomed to Supreme Court justices speaking out much more frequently and informally than they once did. Yet still there was more than one moment in a public conversation Elena Kagan had at Catholic University last month when I almost couldn’t believe what I was hearing.

The justices like to say that their opinions speak for themselves. In the old days, they nurtured the mystique of their delicate yet elevated position in government, rarely if ever revealing their own feelings about the law, American politics or life in general. Anyone who wanted to know what a justice really thought, they claimed, would do best simply to read their rulings.

That is no longer true. Today’s bench is among the most voluble in the court’s history — the justices seem constantly to be writing books, giving speeches, engaging with interviewers and, increasingly, complaining about the institution they serve and (sometimes) the colleagues they serve with.

Even by that new standard, Justice Kagan’s comments, which came during an hour-plus sit-down interview at Catholic University’s law school, broke the judicial omertà, both in what she said explicitly about her conservative counterparts’ blasé attitude toward American democracy and in what she appeared to say about the dangerously compromised state of the court in 2026.

The Catholic University law professor J. Joel Alicea, who interviewed Justice Kagan, started the conversation by asking her about rulings involving partisan gerrymandering, voting rights and money in politics, all of which were decided on party-line votes with her and the other Democratic appointees in the minority.

“The court got it wrong” in each of these cases, Justice Kagan said, because of a “lack of appropriate concern or understanding of the consequences of their decisions.” She pointed to the Republican-appointed majority’s evisceration of the Voting Rights Act in April, which was followed almost immediately by a mad scramble in states across the South to pass new, more partisan gerrymanders aimed at erasing Black lawmakers’ districts.

Protecting Black political participation and representation was precisely what the Voting Rights Act was enacted to do, she noted. By eliminating the last meaningful tool of that landmark law, she explained, “the court kind of said, ‘Oh, well.’” Whether that was meant in the sense of “we don’t care if Black political representation plummets” or in the sense of “it won’t plummet,” Justice Kagan concluded, “the court has kind of blinded itself to the very deleterious effects of their rulings on how the political system works, and has created a democracy that does not work as well as it should.”

This wasn’t the first time she has leveled such sweeping criticisms; you can find similar charges in her dissenting opinions in that and other democracy-related cases, in which she skewered her right-wing colleagues for misunderstanding the law and disregarding Americans’ democratic rights.

But Justice Kagan was offering this critique off the bench, in public — where the justices know their words carry a special significance, particularly before the midterms. Even more surprising, of all the Democratic appointees, if not all nine justices, Justice Kagan has a reputation as the most restrained and institutionalist.

At a judicial conference in July, Justice Kagan took pains to defend her conservative counterparts against accusations that they were acting as a rubber stamp for the Trump administration. So it was that much more remarkable to hear her admit, just a few months later, such wide-ranging frustrations with her fellow justices.

And she wasn’t done: “This court is deeply conservative, and in that way very different from the court I joined 16 years ago.” That court, she added, “was by no means liberal” — it still had a 5-4 conservative majority and had only months earlier decided Citizens United v. F.E.C., which transformed the role of money in politics (and in which Justice Kagan, then serving as President Obama’s solicitor general, had argued the losing side). Still, as recently as 2017, “nobody in America thought the court was in the pocket of any one group or any one party or any one anything,” she said. “The court had a kind of legitimacy. And when the court has a kind of legitimacy of that kind, it helps to create a stable country.”

Her implication, of course, is that today’s court, dominated by a right-wing supermajority that rules consistently in favor of a longstanding conservative agenda, lacks that “kind of legitimacy” — about as serious a charge as a sitting justice can make.

Justice Kagan had one more dig, which verged on the personal. Reflecting on the role of originalism in the court’s jurisprudence, she said, “I’ve never thought originalism really works,” adding that the “cartwheels” originalists perform to reach their preferred outcomes are “almost embarrassing.” In sum, she said, “the whole project is kind of misconceived, and it’s not a very good match with the Constitution we have.”

Originalism has been the coin of the conservative judicial realm for decades and is currently ascendant at the Supreme Court; as Justice Kagan said ruefully at her own confirmation hearings, “We are all originalists.” Calling it “misconceived” and its practitioners “embarrassing” may sound relatively mild to ears accustomed to the crude invective of the Trump era, but it suggests that the interpersonal conflicts on the bench aren’t getting resolved anytime soon.

I would go so far as to infer a deeper message in Justice Kagan’s remarks: When taken together, her critiques of her colleagues — their disregard for democratic rights, their undermining of the court’s legitimacy and their “misconceived” commitment to originalism — offer a coherent case for reforming the court.

It goes something like this: The conservative majority has been arrogating outsize power to itself over the past several years, claiming the authority to decide many of the most contested questions of American legal and political life, while Congress has stood idly by. Even when the court rules that it has no power to act, as it did in the partisan gerrymandering case, it has “deleterious effects” on democracy, as Justice Kagan pointed out. (That ruling has also disproportionately benefited Republican political interests, which goes to her point about legitimacy.)

Next, pair the court’s arrogation of political power with the fact that the right-wing justices apparently consider themselves accountable to no one. As Justice Samuel Alito wrongly claimed about Congress in 2023, “No provision in the Constitution gives them the authority to regulate the Supreme Court — period.”

Finally, consider this in the broader context of judicial life tenure, a functionally impossible-to-amend Constitution and — to Justice Kagan’s point about originalism — a majority in thrall to a theory of constitutional interpretation that privileges the supposed consensus of people living more than two centuries ago over the values and wishes of those alive today.

Put it all together, and the American people have no way to push the Constitution in a more democratic direction. No way to stop six justices from deciding that protecting democratic rights like voting — “just about the most important thing that the court does,” as Justice Kagan described it at Catholic University — is no longer necessary.

The court’s profoundly antidemocratic attitude was summed up neatly by Chief Justice John Roberts, who said in a 2009 interview: “The most important thing for the public to understand is that we are not a political branch of government. They don’t elect us. If they don’t like what we’re doing, it’s more or less just too bad.”

The chief justice offered one remedy: impeachment followed by conviction in the Senate. However, as he also noted, that has never happened in American history. Impeaching even a single justice would be an enormous lift.

There is a better and easier solution, and Justice Kagan’s critiques last month point directly to it: major court reform imposed by Congress.

Structural failures demand structural repairs. Whether these repairs take the form of term limits, an expanded bench, binding ethics rules, restrictions of the court’s jurisdiction or other measures, they are the only way for the American people, through their elected representatives, to reclaim power over a court gone rogue.

Is this what Justice Kagan was saying, implicitly, in her talk at Catholic University? I can’t be certain, but I’m comfortable speculating.

In this moment of rock-bottom public confidence in the court, Justice Kagan was not unaware that she was speaking outside of the formal boundaries of court decisions, and thus challenging the public appearance of judicial comity. Indeed this may be Kagan’s restraint showing up after all: With her comments, she is ringing alarm bells about the seriousness of problems at the court.

And while the justices may have concluded that they are the final word in interpreting the Constitution, no one gave them power over how we interpret their own words.

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Illustration by Sam Whitney/The New York Times

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“When a clown moves into a palace, he doesn’t become a king, the palace instead becomes a circus. — Turkish proverb,”

 

Hmmmmm…History is repeating itself yet again!

 

Isaiah 59:14

New Living Translation

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You might find these videos enlightening!

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A. R. Bernard: one of many

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How handy would it be if you could make your tattoos invisible for a job interview in the morning, and reveal them again for a party in the evening? This sounds like science fiction, but it may soon be reality.

Researchers at the University of Colorado Boulder have developed invisible tattoo ink than can be revealed with a UV torch and stays visible until switched off with white light. They have published their research in the journal Matter & Light.

They created different motifs with this ink ranging from a lantern that reveals its light when activated, to multicolored scales like those in the much-loved children’s book The Rainbow Fish.

The pigments used in these inks are so-called photochromic dyes(from the Greek “photos”, which means “light” and “chroma”, which means “color”). In other words, they are compounds that change colour when exposed to light. These dyes have been used for years in color-changing sunglasses.

Light carries energy, and photochromic compounds are designed in such a way that this energy is enough to cause a chemical change that alters the shape and therefore the properties of the molecule.

In the case of the “invisible” tattoo ink, two or three seconds of bright ultraviolet (UV) light is enough to form a new ring in the dye molecule, which switches a colorless pigment to a colored one. A variety of colors are available depending on the exact structure of the molecule.

A blast of bright white light reverses the reaction, breaking the ring and turning the colour off again. For a long time, the challenge with this chemistry was that the colored form of the dye was relatively unstable and quickly reverted to the more stable, colorless form—especially at higher temperatures.

Another issue was fatigue: after a certain number of on-off cycles, the dyes degraded and took on a permanent coloured hue. Have you ever bought transition lens sunglasses and noticed that they became less effective over time? This is due to the same deterioration of photochromic compounds in the lenses. But thanks to recent research efforts, remarkably stable dyes have been designed that reliably hold their colour for months and can undergo over 10,000 activation and deactivation cycles without degrading.

Carson Bruns’ team at the University of Colorado Boulder showed that these pigments could be formulated into tattoo inks by encapsulating them in poly(methyl methacrylate) (PMMA), a polymer approved for medical use in bone cement, dentures and intraocular lenses. This family of inks is known as PhotoTat.

Time to market

So, when will you be able to get one of these switchable tattoos? A red pigment was already launched in 2024 under the name Magic Ink by Colorado-based biotech company Hyprskn. A 2 millilitre (ml) vial will set you back £77, which is about 100 times more expensive than regular tattoo ink due to the specialised dyes and formulation process required. The ink is fully compliant with the EU’s Reach (Registration, Evaluation, Authorisation and Restriction of Chemicals) safety regulations.

Now, Bruns’ research team has developed three more PhotoTat inks – blue, magenta and yellow – that can combine into 16 other colours. “So far,” Bruns says, “the only person who’s tested this ink is me. I actually have hundreds of these tattoos on my legs now and they’ve all gone really well.”

Some challenges remain though: direct sunlight contains enough UV radiation to activate the tattoos unless they are protected by sunscreen. Indoor light will slowly switch them off over a period of several days.

In addition, the blue ink currently degrades after only 10–100 activations, leaving a permanent, purple-coloured mark. Most importantly, the inks need to undergo thorough toxicity and safety testing before they can be rolled out to tattoo shops for general use, which will likely take several years. Don’t get your hopes up just yet about your new “business during the day, party at night” look.

When Hyprskn launched Magic Ink, the reception in the tattoo community was mixed. While some tattoo enthusiasts viewed it as a revolutionary creative tool, others thought it was an overpriced gimmick. Bruns does not only see his photochromic tattoo inks as fashion accessories, however.

He also envisages medical applications, for example for patients who need permanent skin markings to guide radiation therapy or identify sites for biopsies. Bruns argues that these markings “become a permanent reminder of a traumatic experience” which can be mitigated by making the tattoo invisible once it is no longer needed in a clinical setting.

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Take Aways

• MIT researchers engineered M13 bacteriophage particles to control how densely they display antigens, strengthening targeted immune responses in mice.
• Higher-density vaccines improved protection in melanoma and colorectal tumor-cell challenge experiments, with a roughly sevenfold higher fraction of neoantigen-specific T cells in the colorectal model.
• The platform could support personalized cancer vaccines, but this study vaccinated mice before tumor-cell injections and did not establish effectiveness in people.

 

Packing more cancer targets onto a tiny viral scaffold helped mice mount a stronger defense against injected tumor cells. The finding points to a controllable feature of vaccine design: how densely a delivery particle displays the molecular markers that immune cells learn to recognize. It could help researchers refine personalized cancer vaccines.

The MIT study, published in Advanced Healthcare Materials, uses an engineered bacteriophage called M13. Shengnan Huang, a research scientist at the Koch Institute for Integrative Cancer Research, led the work. Senior author Angela Belcher is MIT’s James Mason Crafts Professor of Biological Engineering and Materials Science and Engineering.

The results come from laboratory experiments and small mouse studies, not clinical trials. The work focused on improving the design of a vaccine formulation. Mice received vaccines before researchers injected tumor cells, testing protection against a later challenge. Whether the same density adjustments improve treatment of established tumors requires further testing.

Turning a bacterial virus into a vaccine carrier

M13 is a bacteriophage, a virus that infects bacteria rather than human cells. Its single-stranded DNA sits inside a long protein shell, or capsid. The engineered particles in this study measured approximately 200 nanometers in length.

The researchers attached antigens, molecular targets recognized by immune cells, to a major capsid protein called pVIII. Each particle contained a mixture of ordinary pVIII and antigen-bearing versions. Altering that mixture changed the density of antigen displayed along the particle’s surface.

The viral DNA also supplies an immune-stimulating signal through Toll-like receptor 9, or TLR9. That gives M13 its own adjuvant activity, helping amplify the response to its antigen cargo. Combining the target and this immune activation signal within one scaffold is part of the platform’s appeal.

Making antigen density adjustable

Huang first worked with SIINFEKL, a short peptide commonly used as a model antigen in mouse immunology. Adding negatively charged amino acids alongside it helped antigen-bearing proteins assemble into the capsid. Changing where the proteins were produced in the genetic system further altered their relative abundance.

The team also introduced a regulatory mutation that reduced production of the antigen-bearing protein. Together, these methods adjusted its proportion from about 6% to 70.4% of the major coat proteins. That corresponds to roughly 36 to 420 antigen-bearing copies per 200-nanometer particle.

The highest density came with a manufacturing drawback: particle yield fell substantially. A mutation lowered display to approximately 34.7% while improving production. The work therefore identified a trade-off between maximizing antigen display and producing enough stable particles for further development.

“The antigen is the specific target we want to initiate the immune response against, which means we have to ensure the right dose of antigen to make sure that we can have a strong immune response,” Huang says. Her explanation highlights why the team investigated both particle design and the resulting immune activity.

How immune cells handled the particles

The researchers compared particles carrying approximately 6% and 34.7% antigen-bearing coat proteins. In laboratory tests, dendritic cells took up the higher-density particles about 2.8 times more efficiently. These antigen-presenting cells help teach T cells which molecular targets to recognize.

Higher-density particles also improved antigen presentation, the display of processed peptide fragments on the immune cell’s surface. Comparable presentation required roughly half as much particle uptake with the denser version. This suggests that changing surface display affected more than the number of particles reaching a cell.

Not every immune measurement increased. The two versions produced similar results for a dendritic-cell activation marker and TLR9 activation, consistent with their identical DNA cargo. The precise reasons for the uptake and presentation differences remain unresolved, including possible effects on surface charge and intracellular processing.

The particles also remained structurally stable in the reported tests. Blood measurements in mice showed little induction of two inflammatory signals, IL-6 and TNF-alpha. Those limited findings support further development but cannot establish a vaccine’s safety in people or rule out other adverse effects.

Testing protection against later tumor challenges

Mice received equal numbers of the two particle types on days zero and seven. On day 15, researchers injected melanoma cells engineered to express SIINFEKL. The higher-density vaccine produced stronger protection, slower tumor progression and a larger fraction of antigen-specific CD8 T cells, which can attack matching tumor cells.

That T-cell fraction rose from approximately 7.4% to 17.5%. The reported melanoma experiments included five to six mice per group for key immune and tumor measurements. These findings add to research investigating how nanoparticle vaccines can prepare an immune response before tumor exposure.

The researchers then switched to a mutated ADPGK peptide found in the mouse colorectal cancer model MC-38. Such tumor-specific targets are called neoantigens. Increasing their display raised the neoantigen-specific CD8 T-cell fraction from approximately 1.1% to 7.4%, a roughly sevenfold increase.

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Artist’s illustration of antigen-coated M13 particles interacting with an immune cell. MIT researchers found that denser antigen displays strengthened targeted immune responses and improved tumor protection in mice vaccinated before exposure to cancer cells. (CREDIT: The Brighter Side of News)

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A federal judge in Alaska has dismissed the Trump administration’s lawsuit that pre-emptively challenged the results in a U.S. Senate race featuring two candidates with the same name — a Republican incumbent and another man who could be a spoiler.

The ruling is the latest in a series of court defeats for the Trump administration, which has been seeking to intervene in state-administered elections.

On Friday, the U.S. District Court in California blocked the administration from threatening to prosecute state and local election officials who do not comply with the department’s directives on handling ballots.

Also on Friday, a federal appeals court panel denied a request to order California officials to set aside about 20,000 mail-in ballots that the administration claimed had been sent to possible noncitizens.

In Alaska, the Justice Department filed its lawsuit last month at President Trump’s direction, asking the judge to block certification of the state’s U.S. Senate election results if Senator Daniel S. Sullivan loses but would have won had votes cast for Daniel J. Sullivan, a retired teacher, gone to the incumbent instead.

In that scenario, the suit also demands an investigation into whether voters who selected the retired teacher actually intended to vote for the senator.

Federal officials have not made clear how an investigation into anonymous ballots would be conducted.

In her Sunday ruling, Chief Judge Sharon Gleason of U.S. District Court in Alaska wrote that she did not see how the federal government’s proposed solution to any confusion would solve the problem if it even existed — or how the approach could work given the right to a secret ballot is a core principle of American democracy.

The federal government, she wrote, “offers no rebuttal to the concerns regarding preservation of the secrecy of voting and provides no explanation of how its request for ballot segregation and a court-ordered investigation by law enforcement officers into certain voters’ intent could be implemented while preserving the secrecy of the ballot.”

Kiersten Pels, a spokeswoman for the Department of Justice, said the administration plans to appeal the dismissal and noted that the judge didn’t not address “the argument of the United States that Daniel J. Sullivan (a/k/a Decoy Dan) entered the race as a frivolous candidate to confuse voters.”

The administration’s lawsuit accuses Daniel J. Sulivan of trying to “dupe Alaska’s voters into believing that he is Senator Sullivan.” Daniel J. Sullivan has said he voted for Democrats in the last three presidential races and for Mary Peltola, the current Democratic Senate nominee on the ballot, in her 2022 and 2024 campaigns for Congress.

The suit also notes that he switched his party affiliation from Independent to Republican only when he filed to run, and that his campaign website uses the same dark blue and yellow color scheme as the incumbent’s.

A New York Times investigation revealed that a Democratic operative connected to Ms. Peltola’s campaign and the Democratic Senatorial Campaign Committee enlisted Daniel J. Sullivan to run as part of a broader effort to recruit independent and third-party candidates who might peel votes away from the incumbent.

Gov. Mike Dunleavy, a Republican, has ordered a criminal investigation into the Peltola campaign even as the state elections division, overseen by his lieutenant governor, also a Republican, fought the Trump administration’s civil lawsuit.

Ms. Peltola and national Democrats have denied any connection to Daniel J. Sullivan’s candidacy, and they joined the civil case as additional defendants along with national Democrats, the League of Women Voters and Common Cause, a self-described nonpartisan government watchdog organization.

Daniel S. Sullivan, the incumbent senator, promised in an interview with CNN Sunday to support any election results but also suggested, without offering explanation or details, that the election could be “stolen.”

In its defense in the Justice Department’s lawsuit, lawyers with the state of Alaska noted that state courts had already rejected an attempt by the state’s elections agency to take Daniel J. Sullivan off the ballot and that the final ballot was designed to differentiate between the two men: It lists the senator as “Dan S. Sullivan” and notes his party affiliation and incumbency, and the other man is “Daniel J. Sullivan Jr.” with no party affiliation included.

Alaska also uses ranked choice voting in state and federal general elections, meaning voters are familiar with the system. Any voter confused by the existence of two Dan Sullivans could simply rank both candidates.

Judge Gleason had already expressed skepticism of the Trump administration’s case in a ruling last month agreeing to a speedy hearing. In that order, she pointed out that the federal lawsuit came after Alaskans had already begun casting ballots for November and nearly four months after the Alaska Supreme Court directed the state Division of Elections to include Daniel J. Sullivan on the ballot.

In Sunday’s dismissal ruling, she noted that federal lawyers, in their filings, said they were not attempting to interfere in the time, place and manner of Alaskan elections — matters the U.S. Constitution leaves in the hands of states.

But, Judge Gleason said, the federal government’s proposed answers to any voter confusion were “a court order preventing the State from certifying the election if certain circumstances occur; a court order requiring the State to segregate and preserve certain ballots; and a court order permitting the United States to conduct an investigation into the intent of those voters who cast ballots for Daniel J. Sullivan.

“These requests certainly involve the time, place, and manner of Alaska’s election,” she wrote.

If anything, the judge added, such federal intervention amid an ongoing election would cause the precise sort of voter confusion the administration says it is trying to prevent.

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Sullivan, left, a candidate in Alaska’s U.S. Senate race, and incumbent U.S. Senator Dan S. Sullivan, right.Becky Bohrer/Associated Press, Doug Mills/The New York Times

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For seven years, molecular biologist Ionut Dumitru and his colleagues played what felt like the world’s most exhausting game of hide-and-seek.

Yet instead of peeking around doors or under beds, they were examining brain tissue in a lab at the Karolinska Institute in Sweden, looking for something that had long evaded neuroscientists: concrete proof that the adult brain can form new neurons via a process called neurogenesis. Scientists have spent decades debating whether this is possible. As soon as one paper turned up positive clues, another would yield nothing at all.

But it seems the search may finally be over. A slew of new findings, including those from Dumitru and his team, have revealed near-certain evidence that adult neurogenesis occurs in the human hippocampus, part of the brain central to learning and memory. The discovery is forcing us to rethink long-held assumptions about our most indispensable organ, from how it functions to how it changes with age.

Even more exciting is the potential neurogenesis holds for brain regeneration. Some of our most devastating medical conditions, including Alzheimer’s, stroke and amyotrophic lateral sclerosis (ALS), involve neurons dying at massive scale. If the brain is capable of replacing some of those lost neurons, we may be able to harness and enhance that ability, stimulating neurogenesis to help treat neurological conditions that are currently incurable.

“To many of us, we think the question is no longer whether it exists or not,” says neuroscientist Hongjun Song at the University of Pennsylvania. “It’s, how can we take advantage of that?”

Neurons are the brain’s key messengers, transmitting the signals that underpin our most basic functions, from moving and talking to thinking and dreaming. They form when a stem cell – which can morph into other cell types – transforms into a “parent” progenitor cell, which then births an immature neuron that eventually matures.

Scientists long believed this process played out only during development in the womb and, to a lesser degree, during childhood and adolescence. In other words, humans were born with essentially all the neurons they would ever have. The brain would change in many ways over one’s lifetime – forming new connections between neurons and pruning away those that were no longer necessary – but it wasn’t going to get a windfall of new neurons. Or at least, so we thought.

In the early 1960s, Joseph Altman, a biologist at the Massachusetts Institute of Technology, went against the grain by looking for signs of neurogenesis in adult rats. He injected the animals with a radioactive tracer used to track cell division, then identified cells bearing it in the rodents’ brains, revealing what appeared to be freshly generated neurons.

But the finding was widely panned by the neuroscience community. The idea that adult neurogenesis was impossible “had really been embedded within the scientific literature”, says Fred “Rusty” Gage, a neuroscientist at the Salk Institute for Biological Studies in California.

Altman was apparently undeterred, replicating his findings in the brains of additional rats and then cats. Other researchers eventually joined in, finding adult neurogenesis in species such as canaries and monkeys, and discovering that it seemed to play a role in learning and memory – helping birds learn new songs, for instance.

But whether human brains also pump out new neurons remained an open question. You can’t ethically crack open a living person’s skull and dig around in their brain tissue.

Gage and his colleagues found an ingenious workaround to that problem. In the 1990s, some people being treated for cancer received injections of a chemical called BrdU, which flagged dividing cells so that doctors could monitor disease spread. When five such patients had died, Gage and his colleagues were able to autopsy their brains. Lo and behold, they found BrdU in hippocampal cells – a sign of neurogenesis.

The trouble is that BrdU can sometimes flag cells undergoing repair, not necessarily division. And subsequent studies that used different markers yielded results all over the map. Some showed next to no neurogenesis in the adult brain; others, that the adult hippocampus adds 700 new neurons every single day, on a par with that of a much younger brain.

So, Song and his colleagues pioneered a different approach. Instead of looking for immature neurons with just one or two markers, they analysed the full genetic profile of individual brain cells, searching for the genetic characteristics of freshly generated cells. They discovered immature neurons in people who had died across all stages of life, even up to age 92.

But spotting a young neuron still isn’t enough to prove the adult brain is generating new ones. Neurons can linger in an immature state for a long time, perhaps even an entire lifespan. These Peter Pans of the brain aren’t necessarily created in adulthood; they just aren’t growing up.

The real challenge in proving adult neurogenesis occurs was to capture each stage of the process – and one remained elusive. “Nobody had identified the proliferating progenitors,” says Dumitru. “They could identify immature neurons, they could identify maybe stem cells – so the cells that are at the beginning and end of the trajectory – but nobody identified the proliferating ones.”

To identify these cells, which actually birth new neurons, Dumitru and his colleagues genetically analysed roughly 400,000 brain cells from the hippocampi of people who had died between infancy and adulthood. They used a machine learning model – a type of artificial intelligence – to pinpoint genetic patterns that resembled those seen in progenitors from animals and developing infants.

The researchers almost couldn’t believe it when they spotted the first few progenitors. “It was so difficult to convince ourselves,” says team member Marta Paterlini, a molecular biologist also at the Karolinska Institute.

But after years of testing and re-testing, they finally felt confident their search was over. They found only about 350 progenitor cells – and they weren’t present in all the brains sampled. But by finding any at all, “we showed that there is active neurogenesis” in the hippocampus, says Dumitru. “That cannot be contested.”

Except that, well, some scientists still do. Developmental neurobiologist Arturo Alvarez-Buylla at the University of California, San Francisco, isn’t convinced that machine learning models can reliably categorise cell types. He says the only way to know for certain that adult neurogenesis happens would be to track a stem cell as it transforms into a neuron – a nearly impossible task to do in a living human.

But sceptics like Alvarez-Buylla are increasingly finding themselves outside a coalescing consensus. At least 38 clinical trials related to adult neurogenesis are now under way. “It’s there,” says Sandrine Thuret, a neuroscientist at King’s College London. “The new debate is, what is it for?”

One of the first clues to answering that question comes from the fact that adult neurogenesis appears almost exclusive to the hippocampus, the brain’s headquarters of learning and memory. This region is highly plastic, meaning it can easily reorganise itself and form new connections, helping us to take in and remember new information.

In a study from earlier this year, neuroscientist Orly Lazarov at the University of Illinois College of Medicine and her colleagues found that neurogenesis may play a role in this process. They examined post-mortem hippocampus samples from adults who had Alzheimer’s and adults without cognitive impairments, including “superagers” – people in their eighties or older who had outperformed younger adults on a memory test. On average, superagers had roughly twice as many immature neurons in their hippocampus as adults without cognitive impairments. People with Alzheimer’s had almost none at all.

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Joey Guidone

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