Lucretius in De Rerum Natura in 50 BCE seemed to have a few that were just a bit ahead of everyone else.

Survival of the fittest (book 5):

"In the beginning, there were many freaks. Earth undertook Experiments - bizarrely put together, weird of look Hermaphrodites, partaking of both sexes, but neither; some Bereft of feet, or orphaned of their hands, and others dumb, Being devoid of mouth; and others yet, with no eyes, blind. Some had their limbs stuck to the body, tightly in a bind, And couldn't do anything, or move, and so could not evade Harm, or forage for bare necessities. And the Earth made Other kinds of monsters too, but in vain, since with each, Nature frowned upon their growth; they were not able to reach The flowering of adulthood, nor find food on which to feed, Nor be joined in the act of Venus.

For all creatures need Many different things, we realize, to multiply And to forge out the links of generations: a supply Of food, first, and a means for the engendering seed to flow Throughout the body and out of the lax limbs; and also so The female and the male can mate, a means they can employ In order to impart and to receive their mutual joy.

Then, many kinds of creatures must have vanished with no trace Because they could not reproduce or hammer out their race. For any beast you look upon that drinks life-giving air, Has either wits, or bravery, or fleetness of foot to spare, Ensuring its survival from its genesis to now."

Trait inheritance from both parents that could skip generations (book 4):

"Sometimes children take after their grandparents instead, Or great-grandparents, bringing back the features of the dead. This is since parents carry elemental seeds inside – Many and various, mingled many ways – their bodies hide Seeds that are handed, parent to child, all down the family tree. Venus draws features from these out of her shifting lottery – Bringing back an ancestor’s look or voice or hair. Indeed These characteristics are just as much the result of certain seed As are our faces, limbs and bodies. Females can arise From the paternal seed, just as the male offspring, likewise, Can be created from the mother’s flesh. For to comprise A child requires a doubled seed – from father and from mother. And if the child resembles one more closely than the other, That parent gave the greater share – which you can plainly see Whichever gender – male or female – that the child may be."

Objects of different weights will fall at the same rate in a vacuum (book 2):

“Whatever falls through water or thin air, the rate Of speed at which it falls must be related to its weight, Because the substance of water and the nature of thin air Do not resist all objects equally, but give way faster To heavier objects, overcome, while on the other hand Empty void cannot at any part or time withstand Any object, but it must continually heed Its nature and give way, so all things fall at equal speed, Even though of differing weights, through the still void.”

Often I see people dismiss the things the Epicureans got right with an appeal to their lack of the scientific method, which has always seemed a bit backwards to me. In hindsight, they nailed so many huge topics that didn't end up emerging again for millennia that it was surely not mere chance, and the fact that they successfully hit so many nails on the head without the hammer we use today indicates (at least to me) that there's value to looking closer at their methodology.

Which was also super simple:

Step 1: Entertain all possible explanations for things, not prematurely discounting false negatives or embracing false positives.

Step 2: Look for where single explanations can explain multiple phenomena.

While we have a great methodology for testable hypotheses, the scientific method isn't very useful for untestable fields or topics. And in those cases, I suspect better understanding and appreciation for the Epicurean methodology might yield quite successful 'counterfactual' results (it's served me very well throughout the years, especially coupled with the identification of emerging research trends in things that can be evaluated with the scientific method).

A singleton is hard to verify unless there was a long period of time after its discovery during which it was neglected, as in the case of Mendel.

Yet if your discovery is neglected in this way, the context in which it is eventually rediscovered matters as well. In Mendel's case, his laws were rediscovered by several other scientists decades later. Mendel got priority, but it still doesn't seem like his accomplishment had much of a counterfactual impact.

In the case of Shannon, Einstein, etc, it's possible their fields were "ripe and ready" for what they accomplished - as perhaps evidenced by the fact that their discoveries were accepted - and that they were simply plugged in enough to their research communities during a period of faster global dissemination of knowledge that any hot-on-heels competitors never quite got a chance to publish. But I don't know enough about these cases to be confident.

I can think of a couple cases in which I might be convinced of this sort of counterfactual impact from a scientific singleton:

• All peers in a small, tight-knit research community explicitly stated none of them were even close (though even this is hard to trust - are they being gracious? how do they know their own students wouldn't have figured it out in another year's time?). Do we have any such testimonials for Shannon, Einstein, etc?
• The discovery was actually lost, then discovered and immediately appreciated for its significance. Imagine a math proof written in a mathematician's papers, lost on their death, rediscovered in an antique shop 40 years later, and immediately heralded as a major advance - like if we'd found a proof by Fermat of Fermat's Last Theorem in an attic in 1950.
• Money was the bottleneck. There are many places a billion dollars can be put into research. If somebody launches a billion-dollar research institute in an underfunded subject that's been languishing for decades and the institute they founded starts coming up with major technical advances, that's evidence it was a game-changer. Of course it's possible that billionaire put their money into the field because they had information that the research was coming to fruition and they wanted to get in on something hot, but I probably have more trouble believing they could make such a prediction so accurately than that their money made a counterfactual impact.

A discovery can also be "counterfactually important" even if it only speeds up science a bit and is only slightly a singleton. Let's say that every year, there's one important scientific discovery and a million unimportant ones, and the important ones must be discovered in sequence. If you discover 2025's important discovery in 2024, all the future important discoveries in the sequence also arrive a year earlier. If each discovery is worth $1 billion/year, then you've now created $1 billion counterfactual dollars per year every year as long as this model holds.

Possibly Wantanabe's singular learning theory. The math is recent for math, but I think only like '70s recent, which is long given you're impressed by a 20-year math gap for Einstein. The first book was published in 2010, and the second in 2019, so possibly attributable to the deep learning revolution, but I don't know of anyone making the same math--except empirical stuff like the "neuron theory" of neural network learning which I was told about by you, empirical results like those here, and high-dimensional probability (which I haven't read, but whose cover alone indicates similar content).

• Scott Garrabrant's discovery of Logical Inductors. 

I remembered hearing about the paper from a friend and thinking it couldn't possibly be true in a non-trivial sense. To someone with even a modicum of experience in logic -  a computable procedure assigning probabilities to arbitrary logical statements in a natural way is surely to hit a no-go diagonalization barrier. 

Logical Inductors get around the diagonalization barrier in a very clever way.  I won't spoil how it does here. I recommend the interested reader to watch Andrew's Critch talk on Logical Induction. 

It was the main reason convincing that MIRI != clowns but were doing substantial research.  

The Logical Induction paper has a fairly thorough discussion of previous work.  Relevant previous work to mention is de Finetti's on betting and probability,  previous work by MIRI & associates (Herreshof, Taylor, Christiano, Yudkowsky...), the work of Shafer-Vovk on financial interpretations of probability & Shafer's work on aggregation of experts.  There is also a field which doesn't have a clear name that studies various forms of expert aggregation. Overall, my best judgement is that nobody else was close before Garrabrant. 

• The Antikythera artifact: a Hellenistic Computer.  
  • You probably learned heliocentrism= good, geocentrism=bad, Copernicus-Kepler-Newton=good epicycles=bad. But geocentric models and heliocentric models are equivalent, it's just that Kepler & Newton's laws are best expressed in a heliocentric frame. However, the raw data of observations is actually made in a geocentric frame. Geocentric models stay closer to the data in some sense. 
  • Epicyclic theory is now considered bad, an example of people refusing to see the light of scientific revolution. But actually, it was an enormous innovation. Using high-precision gearing epicycles could be actually implemented on a (Hellenistic) computer  implicitly doing Fourier analysis to predict the motion of the planets. Astounding. 
  • A Roman author (Pliny the Elder?) describes a similar device in posession of Archimedes of Rhodes. It seems likely that Archimedes or a close contemporary (s) designed the artifact and that several were made in Rhodes. 

Actually, since we're on the subject of scientific discoveries 

• Discovery & description of the complete Antikythera mechanism.  The actual artifact that was found is just a rusty piece of bronze. Nobody knew how it worked.  There were several sequential discoveries over multiple decades that eventually led to the complete solution of the mechanism.The final pieces were found just a few years ago. An astounding scientific achievement. Here is an amazing documentary on the subject: 

Antonie van Leeuwenhoek, known as the Father of Microbiology, made the first microscopes capable of seeing microorganisms and is credited as the person who discovered them. He kept his lensmaking techniques secret, however, and microscopes capable of the same magnification didn't become generally available until many, many years later.

If you'll allow linguistics, Pāṇini was two and a half thousand years ahead of modern descriptive linguists.

Maybe Galois with group theory? He died in 1832, but his work was only published in 1846, upon which it kicked off the development of group theory, e.g. with Cayley's 1854 paper defining a group. Claude writes that there was not much progress in the intervening years:

The period between Galois' death in 1832 and the publication of his manuscripts in 1846 did see some developments in the theory of permutations and algebraic equations, which were important precursors to group theory. However, there wasn't much direct progress on what we would now recognize as group theory.

Some notable developments in this period:

1. Cauchy's work on permutations in the 1840s further developed the idea of permutation groups, which he had first explored in the 1820s. However, Cauchy did not develop the abstract group concept.

2. Plücker's 1835 work on geometric transformations and his introduction of homogeneous coordinates laid some groundwork for the later application of group theory to geometry.

3. Eisenstein's work on cyclotomy and cubic reciprocity in the 1840s involved ideas related to permutations and roots of unity, which would later be interpreted in terms of group theory.

4. Abel's work on elliptic functions and the insolubility of the quintic equation, while published earlier, continued to be influential in this period and provided important context for Galois' ideas.

However, none of these developments directly anticipated Galois' fundamental insights about the structure of solutions to polynomial equations and the corresponding groups of permutations. The abstract concept of a group and the idea of studying groups in their own right, independent of their application to equations, did not really emerge until after Galois' work became known.

So while the 1832-1846 period saw some important algebraic developments, it seems fair to say that Galois' ideas on group theory were not significantly advanced or paralleled during this time. The relative lack of progress in these 14 years supports the view of Galois' work as a singular and ahead-of-its-time discovery.

That the earth is a sphere:

Today, we have lost sight of how counter-intuitive it is to believe the earth is not flat. Its spherical shape has been discovered just once, in Athens in the fourth century BC. The earliest extant reference to it being a globe is found in Plato’s Phaedo, while Aristotle’s On the Heavens contains the first examination of the evidence. Everyone who has ever known the earth is round learnt it indirectly from Aristotle.

Thus begins "The Clash Between the Jesuits and Traditional Chinese Square-Earth Cosmology". The article tells the dramatic story of how some Jesuits tried to establish the spherical-Earth theory in 16th century China, where it was still unknown, partly by creating an elaborate world map to gain the trust of the emperor.

They were ultimately not successful, and the spherical-Earth theory only gained influence in China when Western texts were increasingly translated into Chinese more than two thousand years after the theory was originally invented.

Which makes it a good candidate for one of the most non-obvious / counterfactual theories in history.

I sometimes had this feeling from Conway's work, in particular, combinatorial game theory and surreal numbers to me feel closer to mathematical invention than mathematical discovery. This kind of things are also often "leaf nodes" on the tree of knowledge, not leading to many followup discoveries, so you could say their counterfactual impact is low for that reason.

In engineering, the best example I know is vulcanization of rubber. It has had a huge impact on today's world, but Goodyear developed it by working alone for decades, when nobody else was looking in that direction.

Wegener’s theory of continental drift was decades ahead of its time. He published in the 1920s, but plate tectonics didn’t take over until the 1960s.  His theory was wrong in important ways, but still.

Pasteur had (also highly "counterfactual") help I think! Ignaz Semmelweis worked in this maternity ward where the women & babies kept dying.  The hospital had opened up some investigations over the years as to the cause of death but kept closing them with garbage explanations. He went somewhere else for a while and when he got back he noticed that the death numbers were down in his absence. Then he noticed his hands smelled like death after one of his routine autopsies and he was about to go plunge them in some poor mother! He had washed them but just with regular soap. If he put some bleach in the washwater then his hands didn't stink. He connected the dots. He had killed hundreds of mothers & babies but wrote a book about it anyway and thereby popularized disinfection (and strongly suggested the root cause of disease).

Probably the main reason that germ theory took so long to work out is that the people with the right evidence were too guilty and ashamed to share it. 

Set theory is the prototypical example I usually hear about. From Wikipedia:

Mathematical topics typically emerge and evolve through interactions among many researchers. Set theory, however, was founded by a single paper in 1874 by Georg Cantor: "On a Property of the Collection of All Real Algebraic Numbers".

Peter J. Bowler suggests that evolution by natural selection is this in his book "Darwin Deleted" - given that in real life, there was an "eclipse of Darwinism", he suggests that without Darwin, various non-Darwinian theories of evolution would have been developed further, and evolution by natural selection would have come rather late

An example that's probably * not* a highly counterfactual discovery is the discovery of DNA as the inheritance particle by Watson & Crick [? Wilkins, Franklin, Gosling, Pauling...].

I had great fun reading Watson's scientific-literary fiction the Double Helix. Watson and Crick are very clear that competitors were hot on their heels, a matter of months, a year perhaps.

EDIT: thank you nitpickers. I should have said structure of DNA, not its role as the carrier of inheritance.

Here are some candidates from Claude and Gemini (Claude Opus seemed considerably better than Gemini Pro for this task). Unfortunately they are quite unreliable: I've already removed many examples from this list which I already knew to have multiple independent discoverers (like e.g. CRISPR and general relativity). If you're familiar with the history of any of these enough to say that they clearly were/weren't very counterfactual, please leave a comment.

• Noether's Theorem
• Mendel's Laws of Inheritance
• Godel's First Incompleteness Theorem (Claude mentions Von Neumann as an independent discoverer for the Second Incompleteness Theorem)
• Feynman's path integral formulation of quantum mechanics
• Onnes' discovery of superconductivity
• Pauling's discovery of the alpha helix structure in proteins
• McClintock's work on transposons
• Observation of the cosmic microwave background
• Lorentz's work on deterministic chaos
• Prusiner's discovery of prions
• Yamanaka factors for inducing pluripotency
• Langmuir's adsorption isotherm (I have no idea what this is)

Fun question!

IMO Edison and Shannon are both strong candidates for quite different reasons.

Edison solved a bunch of necessary problems in one go when building a working, commercializable lighting system. He did this in an area where many others had only chipped away at corners of the problem. He was not the first to the area...but I don't think there are any strong claims that the area would have come along nearly as quickly if not for him/his team. I talk about this in-depth in a Works in Progress piece on Edison as an exception technical entrepreneur.

As far as Shannon goes, I'm not saying he initially published on his two major discoveries much earlier than others would have initially published...but Shannon had a sort of uncanny ability to open and largely close a sub-field all in one go. This is rare in scientific branch creation. Usually a process likes this takes something like 5-10 people something like 5-20 years to do. My FreakTakes piece on the early years of molecular biology give a sort of blow-by-blow of what this often looks like. Shannon's excellence helped circumvent a lot of that. So IMO the thoroughness of his thinking was a huge time-saver.

Maybe Hanson et al.'s Grabby aliens model? @Anders_Sandberg  said that some N years before that (I think more or less at the time of working on Dissolving the Fermi Paradox), he "had all of the components [of the model] on the table" and it just didn't occur to him that they can be composed in this way. (personal communication, so I may be misremembering some details). Although it's less than 10 years, so...

Speaking of Hanson, prediction markets seem like a more central example. I don't think the idea was [inconceivable in principle] 100 years ago.

ETA: I think Dissolving the Fermi Paradox may actually be a good example. Nothing in principle prohibited people puzzling about "the great silence" from using probability distributions instead of point estimates in the Drake equation. Maybe it was infeasible to compute this back in the 1950s/60s, but I guess it should be doable in 2000s and still, the paper was published only in 2017.

Green fluorescent protein (GFP). A curiosity-driven marine biology project (how do jellyfish produce light?), that was later adapted into an important and widely used tool in cell biology. You splice the GFP gene onto another gene, and you've effectively got a fluorescent tag so you can see where the protein product is in the cell.

Jellyfish luminescence wasn't exactly a hot field, I don't know of any near-independent discoveries of GFP. However, when people were looking for protein markers visible under a microscope, multiple labs tried GFP simultaneously, so it was determined by that point. If GFP hadn't been discovered, would they have done marine biology as a subtask, or just used their next best option?

Fun fact: The guy who discovered GFP was living near Nagasaki when it was bombed. So we can consider the hypothetical where he was visiting the city that day.

The Buddha with dependent origination. I think it says somewhere that most of the stuff in Buddhism was from before the Buddha's time. These are things such as breath-based practices and loving kindness, among others. He had one revelation that made the entire enlightenment thing basically which is called dependent origination.*

*At least according to my meditation teacher, I believe him since he was a neuroscientist and astrophysics masters at Berkeley before he left for India though so he's got some pretty good epistemics.

It basically states that any system is only true based on another system being true. It has some really cool parallels to Gödel's Incompleteness Theorem but on a metaphysical level. Emptiness of emptiness and stuff. (On a side note I can recommend TMI + Seeing That Frees if you want to experience som radical shit there.)

My immediate thought is McClintock's transposable elements. AFAICT, this has only been mentioned by AI-generated lists in this thread, so to fill in a bit more for anyone who doesn't know the story: in the 1940s, McClintock observed genetic and cytological evidence from crosses of corn plants, which she argued could best be explained by assuming certain genetic elements routinely change their position in the genetic map, often breaking other genes when they insert, and restoring those genes again when they excise. For context, the discovery that genes had fixed positions on linear genetic maps that were collinear with chromosomes was still relatively new (1913), and the field of genetics was largely consumed by the job of determining these maps. Her interpretation was therefore very much against the current, and it was mostly dismissed and derided. But she was right. It wasn't until molecular biology confirmed their existence in the 60s-70s that transposable elements ("jumping genes") became widely accepted. She got the Nobel Prize for her discovery over four decades after she made it. 

I take it the reason for asking for such case studies is that singular discoveries can be exceptionally impactful, so it would be good to enrich for them. Therefore it's of interest to ask what happened to McClintock in the intervening decades. My understanding is that she was able to continue her work the entire time, despite the skepticism of the field, due entirely to the Carnegie Institute. Carnegie Institute created a permanent position at Cold Spring Harbor Lab specifically for her, freeing her from teaching and administrative obligations, but more importantly, shielding her from the need for peer acceptance of her ideas (peer-reviewed grants, peer-reviewed papers). Importantly they backed her permanently and unconditionally, so that she was completely free to pursue whatever drove her curiosity, regardless of anyone else's opinion, even theirs. 

This highlights the huge impact a private benefactor (individual or institution) can have by backing individual innovators. The trick is how to figure out who is worth backing. It's only impactful if one ignores or even actively anti-correlates with the usual metrics that academia rewards; but some or even most marginalized mavericks are in fact crackpots, so anticorrelating isn't enough. One has to be confident in positively judging people or ideas to be worthwhile, without relying on evaluations by leaders and experts.

Grothendiek seems to have been an extremely singular researcher, various of his discoveries would have likely been significantly delayed without him. His work on sheafs is mind bending the first time you see it and was seemingly ahead of its time.

I have previously used special relativity as an example to the opposite. It seems to me that the Michelson-Morley experiment laid the groundwork and all alternatives were  more or less rejected by the time special relativity was formulated. This could be hindsight bias though.

If nobel prizes are any indicator, then the photoelectric effect is probably more counterfactually impactful than special relativity.

I think it's worth noting that small delays in discovering new things would, in aggregate, be very impactful. On average, how far apart are the duplicate discoveries? If we pushed all the important discoveries back a couple of years by eliminating whoever was in fact historically first, then the result is a world that is perpetually several years behind our own in everything. This world is plausibly 5-10% poorer for centuries, maybe more if a few key hard steps have longer delays, or if the most critical delays happened a long time ago and were measured in decades or centuries instead.

Special relativity is not such a good example here when compared to general relativity, which was much further ahead of its time. See, for example, this article: https://bigthink.com/starts-with-a-bang/science-einstein-never-existed/

Regarding special relativity, Einstein himself said:^[1]

There is no doubt, that the special theory of relativity, if we regard its development in retrospect, was ripe for discovery in 1905. Lorentz had already recognized that the transformations named after him are essential for the analysis of Maxwell's equations, and Poincaré deepened this insight still further. Concerning myself, I knew only Lorentz's important work of 1895 [...] but not Lorentz's later work, nor the consecutive investigations by Poincaré. In this sense my work of 1905 was independent. [..] The new feature of it was the realization of the fact that the bearing of the Lorentz transformation transcended its connection with Maxwell's equations and was concerned with the nature of space and time in general. A further new result was that the "Lorentz invariance" is a general condition for any physical theory. 

As for general relativity, the ideas and the mathematics required (Riemannian Geometry) were much more obscure and further afield. The only people who came close, Nordstrom and Hilbert, arguably did so because they were directly influenced by Einstein's ongoing work on general relativity (not just special relativity). 

https://www.quora.com/Without-Einstein-would-general-relativity-be-discovered-by-now 

1. ^{^}

   https://en.m.wikipedia.org/wiki/Relativity_priority_dispute 

Possible example: Laennec's invention of the stethoscope in 1816. Of course we would've come up with it eventually. But note that Laennec got his inspiration from kids playing with sticks and from his prudishness about putting his ear to a woman's chest.

Consider that people have been using sound in diagnosis for millenia. But even something as simple as tapping a finger on another (to e.g. feel and hear the liquid in e.g. your lungs (which you don't want)) was introduced in the mid 1700s by Auenbrugger (though some medieval guy had it too? Not going to count it since it seemed to not be advanced further) and the method also influenced Laennec. Auenbrugger was inspired by his father's wine business - you tap the barrel to see how much fluid is in it!

So, consider: anyone 'could have' come up with either of these for... literal millenia? But they didn't? And the main inspiration was stuff most medical practicioners weren't looking at? Note that Laennec had some experience in flute making that helped him make his stethoscopes.

Lastly (Corvisart)[https://en.wikipedia.org/wiki/Jean-Nicolas_Corvisart] appears to have helped keep the percussion technique of Auenbrugger alive. Laennec learned of percussion from Corvisart's translation of Auenbrugger - and Corvisart expanded on his findings of how to use the sound info. This isn't a fundamental discovery, but it looks like he did have significant impact.

I've tried pointing Deep Research at this, doing a three-turn search. Here's the result, including a GPT-4.5 summary at the end.

• Repeat mentions^[1]: Einstein, Mendel, Ignaz Semmelweis' antiseptic handwashing, Wegener's continental drift, Cantor' set theory, Emmy Noether, McClintock's transposons.
• New candidates: Charles Babbage's analytical engine, Barry Marshall and Robin Warren on Helicobacter pylori causing ulcers, Ada Lovelace's idea of a general-purpose computer, Lev Vygotsky's sociocultural cognition theory, Joseph Altman's adult neurogenesis, Dan Shechtman's quasicrystals.
• Purported common threads: Unconventional background, polymathic skillsets, working in relative isolation.

Hasn't really been insightful for me, but dropping it here in case it'd be useful for someone else.

1. ^{^}

   As in, those already mentioned by people in this post's answers.

First, your non-standard use of the term "counterfactual" is jarring, though, as I understand, it is somewhat normalized in your circles. "Counterfactual" unlike "factual" means something that could have happened, given your limited knowledge of the world, but did not. What you probably mean is "completely unexpected", "surprising" or something similar. I suspect you got this feedback before.

Sticking with physics. Galilean relativity was completely against the Aristotelian grain. More recently, the singularity theorems of Penrose and Hawking unexpectedly showed that black holes are not just a mathematical artifact, but a generic feature of the world. A whole slew of discoveries, experimental and theoretical, in Quantum mechanics were almost all against the grain. Probably the simplest and yet the hardest to conceptualize was the Bell's theorem. 

Not my field, but in economics, Adam Smith's discovery of what Scott Alexander later named Moloch was a complete surprise, as I understand it.