Nature Biomedical Engineering, Published online: 05 October 2026; doi:10.1038/s41551-026-01798-1

A positron emission tomography tracer that directly targets bacterial metabolism by exploiting the phosphotransferase system, a carbohydrate transport pathway absent in mammalian cells, enables selective detection of living bacteria in vivo.

scBaseCount is presently the largest public single-cell RNA-seq repository, containing over 502 million cells across 27 organisms and 75 tissues. An AI agent autonomously discovers, annotates, and uniformly reprocesses all 10× Genomics datasets in the SRA, creating a harmonized, continually updated resource for studying the diversity of cell biology and training AI models.

LongevityBench, Longevity-LLMs, and Longevity Claw evaluate the readiness of the state-of-the-art AI systems for spearheading aging research.

Nature Medicine, Published online: 16 September 2026; doi:10.1038/s41591-026-04625-x

In a prospective study involving 1,785 individuals from four countries, the PANXEON exosome-based biomarker, combined with carbohydrate antigen 19-9 levels, achieves high sensitivity for the detection of early-stage pancreatic cancer.

Nature Medicine, Published online: 16 September 2026; doi:10.1038/s41591-026-04662-6

Sex-specific biological aging clocks across multiple organs and molecular systems show that female and male aging patterns can differ in organ-specific, disease-relevant ways.

Cell Death Discovery, Published online: 16 September 2026; doi:10.1038/s41420-026-03345-y

rhNGF shows neuroprotective efficacy by counteracting oxidative stress and neuroinflammation in a glaucoma mouse model

When Jessica Wachter, a finance professor at the University of Pennsylvania’s Wharton School, wanted to assess AI’s impact on the economy over the next few years, she faced a long list of business and technical uncertainties. So she started with what she calls a “remarkable fact” that is not in question: A handful of so-called hyperscalers are investing huge amounts of money to build AI data centers.

Instead of trying to predict how useful and widely deployed AI models will be, she simply asked how fast the hyperscalers’ earnings will need to grow to justify their spending through 2027, when—she and her collaborator estimate—expenditures will reach nearly $1.1 trillion. It’s a no-nonsense accounting approach to making sense of today’s historical AI buildout.

The results are eye-opening: The AI companies will need to increase their own productivity by a factor of 2.7 to break even by 2030, accounting for the cost of capital and a 15% return, and depreciation of the assets. Not impossible, says Wachter. The result would lead to the kind of economic growth that we saw during the US IT boom over a period of about 10 years starting in the mid-1990s. But, she says, for it to happen by 2030 “that’s a lot of growth compressed into a few years.” And if the hyperscalers cannot meet such profit goals?

“Then they will fall behind on their interest payments, and that risks bankruptcy,” says Wachter, who was previously the SEC’s chief economist and director of its division of economic and risk analysis. If a productivity boom “fails to materialize,” she and her coauthor conclude in their research paper, “the current buildout will be the largest misallocation of capital in history.”  

It doesn’t take superintelligence to realize that today’s large investments in the infrastructure for artificial intelligence come with huge risks. The hyperscalers will spend about $750 billion this year, building massive data centers scattered across the country. And the spending spree shows no signs of slowing. According to some projections, total AI capital investments from the hyperscaler companies—Alphabet, Microsoft, Amazon, Meta, and Oracle (which partners with OpenAI)—could be more than $5 trillion over the next four years.

It’s one of the largest capital investments by any industry in history. But there’s a problem that’s obvious to anyone paying attention.

While the hyperscalers plan to spend trillions, total AI revenues will be around $150 billion to $200 billion this year, says Gary Gensler, who ran the SEC during the Biden administration and is now a professor at MIT’s Sloan School. “The challenge is that the spending does not have commensurate revenues yet. That’s a fact,” he says. “And then the question is, is that an investment that will be paid off in the future?”

At stake in that trillion-dollar question is the financial health of the giant AI companies and the overall US economy—the investments could soon balloon to around 3% of GDP. The answer could also determine the fate of the hugely expensive data centers themselves. 

No one really knows how profitable and useful these multibillion-dollar behemoths will be down the road. Though AI models have made dazzling progress over the last few years, it’s anyone’s guess how much compute capacity we will need. The technology could become more efficient and therefore less dependent on raw computational power. Or demand for AI products could slow, or customers could turn to cheaper models.

The risks, both to investors and to the economy, have become even greater this year, as these AI companies have begun borrowing large amounts of money to build more and more data centers. Free cash flow—operating cash flow minus capital expenditures—is expected to soon dip into negative territory for the group. Even Alphabet, known for generating and hoarding huge amounts of cash, reports in the latest quarter that its impressive revenues of nearly $120 billion were devoured by AI infrastructure spending, leaving it with a free cash deficit of some $5.9 billion—its first shortfall since Google went public in 2004.

In the near term, it’s not a big financial worry for most of the companies. They make a lot of money and have very deep pockets. But debt is expensive, and some investors are losing patience. If future demand for the data centers’ computation power drops, the companies will still be on the hook to pay back the borrowed money. What’s more, the risks are spreading to the rest of the economy as the loans get passed along via various financial mechanisms. 

It won’t be enough to simply cover the enormous price tags of the new data centers. Hyperscalers will also have to pay for the rising costs of capital as they borrow more money. They will need returns that are impressive enough to justify all their spending to investors and creditors. And to add to those concerns, they will have to make up for the depreciation of billions of dollars in chips housed within the facilities—a ticking time bomb buried in the investments.

Performance of the expensive GPU chips at the core of the data centers—such compute electronics represent some 60% of costs—is roughly doubling every two years or so. The pace of progress helps explain the increasing wizardry of the AI models, but it comes with a cost. Owners of AI data centers that come online this year and next will need to spend billions more on the next generation of chips by the end of the decade if they want to stay competitive. Without the investments, says Mihir Kshirsagar at Princeton’s Center for Information Technology Policy, the data centers risk becoming “hulks,” stranded assets “scattered all over the place.”

To put it bluntly: The AI companies need to start making a lot more money. And they need to do it fast. But juicing their earnings alone still won’t be enough to sustain their data-center investments for the long term.

Productivity is everything

At some point, AI is also going to have to create broad economic growth to justify continuing the hyperscalers’ spending spree.

Sloan’s Gensler describes today’s large investments into AI infrastructure as “a parlay bet by the capital markets and the economy.” That means success will require winning three related but independent wagers: Hyperscalers must generate massive revenues, AI must boost widespread economic growth, and both must happen while the powerful but expensive so-called frontier models that rely on the data centers fend off cheaper versions, which many businesses might find good enough.

What makes this so tricky is that each wager depends on the other two but also poses its own challenges.

If the hyperscalers continue to spend huge amounts of money on data centers into the next decade, revenues will need to skyrocket into the trillions. Stijn Van Nieuwerburgh, a finance professor at Columbia Business School, bases his estimates on a scenario in which about 183 gigawatts of planned AI compute capacity is built between 2025 and 2032; he calculates that each gigawatt costs about $41 billion. Assuming a 10% return—the minimum that would be acceptable to most investors—“required” annual revenues will be roughly $3.7 trillion by 2032, he says.

Others get a similar number.

Winning the second part of the bet—productivity growth across the economy—will be crucial to achieving such numbers.

For a few years, AI companies could likely boost their revenues by simply selling subscriptions and tokens to all the businesses clamoring to get into AI. But eventually—and this might be happening already—those paying customers will need to justify their expenses by seeing bottom-line benefits from the technology. AI will need to fulfill its promise of making workers more productive and making businesses more efficient and profitable while expanding their products and services.

In economic jargon, that means customers will need to see productivity growth. Taken together, these results will mean the country is prospering and growing.

“If you don’t get the productivity gains, at some point people are going to sour on AI, and that will bring down investments and it would also limit revenue growth,” says Daron Acemoglu, an MIT economist and 2024 Nobel laureate. For the investments to be sustainable over, say, the next five to 10 years, we definitely “need to see productivity gains,” he says.

Most economists who watch the numbers closely agree that, for now, the economy-wide statistics show little or no productivity growth from AI. There are some hopeful signs it’s on the way, though. In a recent survey of some 6,000 senior business executives in the US, the UK, Germany, and Australia, the vast majority—around 90%—report no increase in productivity over the last three years. But they expect a boost of around 1.45% in total over the next three years; US executives anticipate a 2.25% bump over that time. 

In a follow-up survey, the respondents also reported plans for their businesses to spend more on AI, leading the authors to anticipate some $280 billion in private-sector AI expenditures by the end of 2026.

That’s good news for the hyperscalers. But it comes with a dose of bad news for those worried about AI’s impact on jobs. The executives expect to increase the productivity of their companies by increasing their sales while significantly cutting the number of employees.

If AI improves productivity by destroying jobs, public backlash to the technology—the kind we have seen around data centers, for example—will likely get worse. Perhaps it’s worth adding one more wager to the parlay bet described by Gensler: The public and local communities must feel that they are also benefiting from the massive investments in AI.

And let’s not forget how interdependent these wagers are; if productivity growth comes from companies running models like DeepSeek, then the hyperscalers’ revenues could collapse. If productivity comes from cutting jobs, a public backlash could block many of the planned investments—and stunt anticipated revenues. We will need to win all the wagers for the hyperscalers’ bet to pay off. 

We’re all part of the AI gamble now

It was one thing when the AI companies were spending cash they had accumulated over the years to build their own data centers. Then the risk was largely limited to their own balance sheets and shareholders. But it’s a higher-stakes game when much of the money is borrowed. Morgan Stanley, for one, calculates that more than half of the $2.9 trillion that hyperscalers will spend between 2025 and 2028 to build AI data centers will be financed with “external capital.”

The borrowing is leading some of the companies to engineer complex webs of financing that are becoming intertwined with much of the rest of the economy. “A lot of financial institutions, directly or indirectly, are exposed to these data centers either as lenders, or as guarantors of some of the debt, or as backers of the private credit funds who are funding these data centers,” says Columbia’s Van Nieuwerburgh. “People don’t even know they’re holding this stuff. It’s somewhere deep inside their pension fund. Ultimately, it’s backing their life insurance policies. And that risk is getting distributed everywhere in places that are invisible.”

As the investments in data centers have spiked, the financial engineering has become more byzantine.

Take, for example, Meta’s so-called Hyperion data center under construction in Richland, Louisiana. When the company announced the two gigawatts of compute capacity at a price tag of some $10 billion in late 2024 it was Meta’s largest planned data center. Greeted with much enthusiasm by state and local politicians, the project, located in the rural northeast corner of the state, was seen as a boon to the community. Entergy Louisiana, the state’s largest utility, rushed forward with proposals to build three large natural-gas power plants to service the massive data center.

Then last fall—the projected cost was now $30 billion—the financing got a lot more complex and, to some in the community, a lot more disconcerting. Meta transferred an 80% stake to the large (and troubled) private-credit firm Blue Owl Capital, forming a joint venture called Beignet (like the famed New Orleans pastry) to raise financing for the data center. Meta then signed a series of four-year leases with the joint venture, an arrangement that the company says gives it “long-term strategic flexibility.” To backstop the agreement, Meta provides the venture with what is called a residual value guarantee, in which it will make a cash payment to cover the value of the facility “following any non-renewal or termination of a lease.” Got all that? 

I hope so. The financial wheeling and dealing is actually even more convoluted, with a cast of wholly owned subsidiaries and LLCs. Beignet has set up Laidley LLC, which owns and operates the site as the landlord. In turn, Laidley leases the facilities to Meta’s wholly owned subsidiary Pelican Leap LLC, which is the tenant. And there is a series of four-year leases that cover the different buildings that make up the data center campus. 

It’s not a coincidence, says Van Nieuwerburgh, that the length of the leases matches the expected lifetime of the data center’s GPUs. While Meta has to pay off its loan if it terminates the leases early, that will still leave its investors “with an empty building and no cash flow,” he says. “And then they need to find a new tenant for a huge data center, and good luck with that.”

Meanwhile, Meta is doubling down on its bet. In July, the company announced it was expanding the data center to five gigawatts of compute capacity. The total price tag is now $50 billion (so far, Meta hasn’t said whether Blue Owl will be involved in financing the expansion). Meanwhile, Entergy is now planning to build seven more gas-fired power plants, bringing the total capacity of the facilities to around 7.5  gigawatts—some six times the amount of electricity used by New Orleans.

If the complex financing is a puzzle to many investors and even financial experts, it is even more baffling to those directly affected by the construction of the data center. The main worry concerns how Entergy’s spending on the natural-gas power plants will affect electricity prices, and who will be left paying the bill for the power if Meta walks away.

Entergy says it has a 20-year guarantee from Meta that the company will purchase electricity over that period to cover the costs of the power plants and related infrastructure.  But there are skeptics, especially given how fast the fortunes of the AI industry are changing. “In four years, is Mark Zuckerberg still going to be interested in this? Or is he going to throw in the towel?” asks Paul Arbaje, a senior analyst at the Union of Concerned Scientists, which has been advocating, largely unsuccessfully, for the Louisiana Public Service Commission to provide more transparency around the data center and its financing.

Even if the 20-year deal holds, consumer advocates are worried that Meta or its partners won’t fully cover all the costs, including those associated with operating and maintaining the power plants—and those additional costs that could be passed on to residential ratepayers. What’s more, says Logan Burke, the executive director of the Alliance for Affordable Energy, if Meta doesn’t end up needing as much power as Entergy planned (these projections are not public), consumers could be left paying for the surplus produced by the plants.

And if Meta terminates its leases early? “It gets complicated very quickly,” says Burke, who questions whether the shifting roster of financial entities will honor existing agreements. “That everybody is going to do what they’re saying they’re going to do over the next 20 years is just hard to believe.”

For UCS’s Arbaje the bottom line is this: “They’re making huge bets that these data centers will be worth it. Bet with your own money, not with ratepayer money.”

After the bubble

Predicting when the AI investment bubble will burst is a fool’s errand. But there is little doubt a day of reckoning is coming, given the irrational exuberance that has overtaken the hyperscalers and their investors. Of course, you might argue that this time is different, and that the rules of accounting and lessons of economic history don’t apply—that AI is too transformative. Maybe, but don’t count on it.

“History tells us that at some point you get a retrenchment, and it’s just a question of when and how severe,” says Sloan’s Gensler. It could be that today’s $750 billion spending rate “goes flat” or decreases next year. Or, he suggests, “we’re now in 2028 or 2029, and then all of sudden they’re retrenching because they’ve got enough capacity.” But, he adds, “you can be pretty assured there’ll be a retrenchment.” 

Though a so-called retrenchment might be inevitable, it’s worth keeping in mind that the fates of the financial bubble and the underlying AI technology revolution could be very different. Already, some Silicon Valley insiders are rooting for a crash; in a recent blog post the longtime venture capitalist Vijay Pande wrote that “the coming crash would be the best thing that happens to this technology.” The argument makes some sense. A crash could make AI investments more rational, calm the impulse to build billion-dollar data centers on every vacant field that CEOs fly over, and refocus investors on how to use the technology to create sustainable value.

But we should probably be careful what we wish for. After the bursting of the dot-com bubble at the beginning of the 2000s, hundreds of thousands lost their jobs, large and small companies alike went bankrupt, the economy of Silicon Valley and San Francisco was decimated (at least for a while), and the shocks sent the US into a mild recession in 2001. For the financial community and many tech workers, it was no fun.

Even more devastating for the economy and the average American was the great recession that began in late 2007. Comparing the financial engineering leading up to it and the methods deployed by hyperscalers today is sobering. So-called special purpose vehicles (SPVs) are back! If Columbia’s Van Nieuwerburgh is right about the dangers of letting investments from the hyperscalers get entangled throughout the economy, the fallout could be severe.

But technologies survived and even prospered in the aftermath of both downturns. The early 2000s, even in the face of the dot-com fiasco, were a time of great innovation and tech optimism. The froth came off the spending on silly technologies, helping to focus investments on more promising ones. It’s no coincidence that each of the hyperscalers rose out of the ashes of the crash or started up shortly after. The fiber-optic infrastructure built during the feverish telecom bubble that ran parallel to the dot-com one is still the backbone of much of today’s communication infrastructure; we wouldn’t have Facebook or Amazon or Google without it.

This time, however, we’re facing a unique risk: The huge financial investments by the hyperscalers have ensnared the future of AI itself with the fortunes of the massive data centers spreading around the country. The logic is founded on a deeply held belief about the power of scaling in AI; the bigger you build it, the smarter it gets. That might be true, but it’s unproven and a risky bet.

There are already plenty of red flags, from strong public opposition to the construction of new data centers to the competitive threat from cheaper, good-enough AI models to the rapid improvement of small, local AI models. None of these trends point toward a future dominated by frontier models housed in massive, billion-dollar data centers.

The financial bubble around the colossal spending by the hyperscalers will likely burst eventually—or maybe soon. It might be financially painful, but we’ll survive. Wall Street will survive. AI itself will survive, though it may look different and lose some of today’s hubris. The financial fate and future utility of the massive data centers fueled by trillions of dollars of spending, on the other hand, are far less certain.

Nature Medicine, Published online: 15 September 2026; doi:10.1038/s41591-026-04644-8

In the phase 2 RIO trial, there was delayed viral rebound and resistance to broadly neutralizing antibodies 3BNC117-LS and 10-1074-LS in adult males living with HIV undergoing analytical treatment interruption, and initial reservoir sensitivity to autologous antibodies was associated with a longer time to rebound.

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Spatial multi-omics reveals macrophage states that constrain adaptive immunity in immunosuppressed non-melanoma skin cancer.

Arginine availability regulates arginyl tRNA levels and codon-dependent translation of MHC class I, tuning antigen presentation and shaping anti-viral and anti-tumor immunity.

Sprox-seq enables spatial profiling of protein complexes, surface proteins, and mRNAs in intact tissues by combining proximity ligation with spatial transcriptomics. In human tonsils, Sprox-seq maps germinal center interaction networks, links CD21-CD35 complexes to proliferative programs, reveals interaction-based B cell state transitions, and directly captures B cell-follicular dendritic cell communication.