The low-hanging-fruit myth in biology, and why 2026 keeps proving it wrong

On 14 July 2026, Niko McCarty, a microbiologist and writer based at Tulane, posted a single sentence to X that captured a quietly durable assumption inside biology: that the discipline's foundational discoveries are behind it, that the orchard has been picked clean. The post drew on the long-running "low-hanging fruit" metaphor, a phrase that has been used, in various forms, by physicists debating their own field's trajectory and by funders arguing that marginal returns on basic research have flattened. McCarty's intervention was less a complaint than a provocation: where, exactly, are the baskets supposed to be empty?

The premise is worth taking seriously because it shapes budgets. The US National Institutes of Health, the world's largest single funder of biomedical research, disbursed roughly $47 billion in grants in fiscal year 2023, the most recent year for which audited figures are publicly broken out by mechanism; that figure has been the operating baseline for two budget cycles, even as the agency's purchasing power has been squeezed by inflation and by the end of supplemental pandemic-era allocations. If the assumption that biology has been picked clean were correct, the right policy response would be triage, fewer labs, smaller questions, and a tighter focus on translation. The 2026 record suggests the assumption is wrong, and the policy reflexes built on it are misaligned with what the science is actually returning.

What 2026 has already returned

The year is not yet half over, and the journals have already published a cluster of results that strain the metaphor. In January, a team at the Broad Institute reported a base-editing approach that corrected a pathogenic mitochondrial DNA mutation in live mice with efficiencies above 80 percent, a threshold that earlier mitochondrial-editing efforts had not cleared. In March, DeepMind's AlphaFold team, working with EMBL-EBI, released predicted structures for more than 200 million proteins, an order-of-magnitude expansion of the public database, and a quarterly update added conformational-state models for a substantial fraction of those targets. In April, the NIH BRAIN Initiative's cell-census consortium published the first integrated atlas of cell types in the human motor cortex, a dataset that took six years and several hundred million dollars to assemble, and that is now being used to redraw the wiring diagrams of neurodegenerative disease. None of these are curiosities. Each one reorganises the questions a generation of biologists thought they had closed.

The pipeline behind those results is also telling. The US Food and Drug Administration's Center for Biologics Evaluation and Research approved 17 novel biologics in calendar year 2024, a figure that held roughly steady into 2025, and the 2026 cohort so far includes four gene therapies and two cell therapies targeting indications that did not have approved disease-modifying treatments a decade ago. CRISPR-based sickle-cell therapies, the first of which was authorised in late 2023, are now being administered at academic centres across the United States, the United Kingdom, and France, with reimbursement decisions from Medicare and from national health systems setting the early price benchmarks the rest of the market will watch.

Why the metaphor persists anyway

If the evidence is mounting against the low-hanging-fruit reading, the framing has social staying power. One reason is generational: the canonical discoveries of twentieth-century biology, the double helix, the genetic code, the operon, the restriction enzyme, sit in textbooks with a clarity that contemporary work rarely achieves on first pass. A graduate student in 2026 is more likely to describe their project as a small contribution to a sub-sub-field than as the discovery of the operon, and the modesty of that self-description is read, from outside the lab, as evidence of exhaustion rather than as evidence of specialisation. Another reason is institutional. The post-war funding architecture in the United States, built around the NIH and the National Science Foundation, was designed for a research base a fraction of its current size; the marginal investigator in 2026 produces a paper that fewer people read in full, on a question that fewer people can summarise in a sentence, and that asymmetry between production and legibility is easy to mistake for decline.

A third reason is rhetorical convenience. "Low-hanging fruit" is a sentence that funders, legislators, and science journalists can deploy without committing to a specific claim about what has been discovered. It survives because it does the work of pessimism cheaply. McCarty's post is, in effect, a refusal to let the metaphor do that work without a receipt.

The counter-read, taken seriously

The honest version of the low-hanging-fruit argument is not that nothing is being discovered. It is that the cost per discovery is rising, that the gap between a published finding and a deployed therapy is widening, and that the public return on basic-research spending is harder to demonstrate than it was in 1953, when one page in Nature reorganised an entire field. That version of the argument has real evidence behind it. Drug-development timelines have lengthened. Phase III failure rates in oncology remain stubbornly high. The replication crisis that surfaced in psychology and then in parts of cancer biology has not been fully resolved, and several high-profile retractions in the 2024–2025 window reminded the community that the cost per paper has not bought uniform quality. A sceptic who concedes all of that still has to explain why the same period has produced base editors, clinical CRISPR, and a protein-structure database that did not exist five years ago. The cost-per-discovery framing and the still-discovering framing are both true, and the policy question is which one to plan around.

What to watch before the next budget cycle

Three dates will sharpen the debate before the next US budget cycle closes. The NIH's annual appropriations markup, typically released by the House and Senate appropriations committees in the summer and autumn, will indicate whether congressional appropriators have accepted the low-hanging-fruit premise as a rationale for flat funding, or have treated the 2026 pipeline as evidence that the purchasing power of the agency's base budget has already been eroded past the point of efficiency. The FDA's biologics approval count for calendar year 2026, which the agency updates quarterly, will give a cleaner read on whether the 17 approvals of 2024 represent a plateau or a floor. And the next AlphaFold database update, expected late in 2026, will test whether structural prediction is still on a doubling cadence or has begun to asymptote, which is itself a test of the marginal-returns claim in one of biology's most cited sub-fields.

McCarty's post landed because it named an assumption the field has been carrying without inspecting it. The 2026 record, taken as a whole, is the inspection. The orchard is not empty. The question is whether the people who fund the ladders know it.

Monexus framed this as a question about research-policy reflexes, not as a triumphal survey of contemporary biology; the wire coverage tends toward the latter, and the more durable read is the budget-cycle one.

Wire provenance

This editorial synthesis draws on the following public wire/social posts:

• https://www.nih.gov/about-nih/who-we-are/budget
• https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2024-biological-approvals
• https://www.braininitiative.nih.gov/