Famous Scientific Papers Rejected Before Publication: 5 That Changed Science

Every researcher who's been desk rejected thinks, even if just for a second, "maybe my work just isn't good enough."

So here are five papers that were desk rejected. Then went on to win Nobel Prizes.

The Krebs cycle paper

In June 1937, Hans Krebs submitted a short manuscript to Nature describing the citric acid cycle, the metabolic pathway that converts food into energy in virtually every living cell. Four days later, he got a rejection letter. The editor said the journal had "already sufficient letters to fill correspondence columns for seven or eight weeks" and suggested he try somewhere else.

Krebs sent the paper to Enzymologia, where it was published that same year. In 1953, he won the Nobel Prize in Physiology or Medicine for the discovery. In 1988, seven years after Krebs died, an anonymous Nature editor published a letter calling the original rejection an "egregious error."

The rejection wasn't even about the science. The editor never read the paper. They just didn't have room.

The Higgs boson paper

In 1964, Peter Higgs submitted a two-page paper to the journal Physics Letters predicting the existence of the particle that would later bear his name. The paper was rejected. No review. Just a note that it didn't warrant publication.

Higgs added a paragraph, sent it to Physical Review Letters instead, and it was accepted. Forty-eight years later, the particle was experimentally confirmed at CERN. Higgs won the Nobel Prize in 2013.

The paper the first journal didn't want has been cited over 4,000 times.

The quasicrystal discovery

Dan Shechtman discovered quasicrystals in 1982. His lab director told him to go read a textbook. He was asked to leave his research group. When he tried to publish, the paper was rejected from Journal of Applied Physics.

He got it published in Physical Review Letters in 1984. For years, the response ranged from skepticism to open mockery. Linus Pauling said "there is no such thing as quasicrystals, only quasi-scientists." Shechtman won the Nobel Prize in Chemistry in 2011.

The CRISPR mechanism paper

Before CRISPR became the most talked-about technology in biology, Virginijus Šikšnys submitted a paper in 2012 demonstrating that Cas9 could be programmed to cut specific DNA sequences, a finding that would help launch the gene-editing revolution. Cell rejected it. The paper was ultimately published in PNAS months later, by which time Doudna and Charpentier had published their landmark paper in Science. Doudna and Charpentier won the 2020 Nobel Prize in Chemistry. Many scientists believe Šikšnys would have shared the prize if Cell hadn't delayed his work by months.

The mRNA vaccine paper

In the mid-2000s, Katalin Karikó and Drew Weissman submitted a paper to Nature showing that chemically modified mRNA could avoid triggering the body's immune defenses, a finding that would become the foundation of the Pfizer and Moderna COVID-19 vaccines. Nature desk rejected it, calling it an "incremental contribution."

The paper was published in Immunity in 2005. For years, almost nobody cited it. Karikó was demoted from her faculty position at Penn because her mRNA research was considered unproductive. Then a pandemic hit. In 2023, Karikó and Weissman won the Nobel Prize in Physiology or Medicine for the work Nature had called incremental.

Two more worth knowing

The radioimmunoassay paper

In 1955, Rosalyn Yalow and Solomon Berson submitted a paper to the Journal of Clinical Investigation showing that the body produces antibodies against insulin: a finding that implied insulin was immunogenic, which contradicted accepted immunology. The journal's reviewers rejected this framing outright. Yalow and Berson were required to remove every instance of the word "antibody" from the paper before it would be published. The term "insulin-binding protein" was substituted throughout. Their data was unchanged.

The technique they developed to prove the finding: radioimmunoassay, the ability to measure vanishingly small concentrations of biological molecules using radioactive tracers: became one of the most widely used tools in medicine. In 1977, Rosalyn Yalow won the Nobel Prize in Physiology or Medicine (Berson had died in 1972 and could not be awarded posthumously). The word "antibody" now appears routinely in the published literature they helped create.

The H. pylori paper

Barry Marshall and Robin Warren spent years trying to publish the evidence that peptic ulcers are caused by bacterial infection: specifically by a bacterium now called Helicobacter pylori. The scientific consensus at the time was that the stomach's acid environment was sterile. Bacteria simply could not survive there.

Their initial abstract, submitted to a Gastroenterological Society meeting in 1983, was rejected as one of the bottom-ranked submissions. When they managed to present, their data were met with disbelief. Marshall was so frustrated that in 1984 he drank a solution containing H. pylori, developed gastritis, documented it, and treated himself with antibiotics. The paper eventually appeared in The Lancet in 1984. In 2005, Marshall and Warren won the Nobel Prize in Physiology or Medicine. Standard treatment for peptic ulcers shifted from lifelong acid suppression to a one-week antibiotic course.

What these stories actually tell you

It's tempting to read these as "don't worry, rejection doesn't matter." That's not quite right. What they tell you is something more specific:

Desk rejection reflects journal fit, not scientific quality. The Higgs paper was rejected because it didn't match what that journal wanted at that moment. Not because the physics was wrong. Not because the evidence was weak. The Krebs cycle paper wasn't even read. Nature just had a full queue.

The same work can be perfect for one venue and wrong for another. Higgs added one paragraph and published elsewhere. Karikó's paper went from "incremental" at Nature to foundational in Immunity. The science didn't change. The targeting did.

Persistence matters, but blind persistence doesn't. None of these researchers just resubmitted the same paper to the same journal. They found a different home, one that was actually looking for what they had.

Timing isn't always in your control. Šikšnys's delay at Cell may have cost him a Nobel Prize. Karikó's work sat mostly uncited for over a decade before a pandemic proved its importance. Sometimes the world catches up to you.

If you just got desk rejected, you're in good company. The question isn't whether your work is good. It's whether you sent it to the right place at the right time. Figure that out, and try again.

What these stories actually tell us about desk rejection

The papers above share one thing: they were eventually published, and they changed their fields. But that outcome required the authors to keep submitting, often for years, to journals that recognised the work.

The lesson is not that desk rejection doesn't matter. It's that desk rejection from the wrong journal is survivable: and that the right journal for a paper is sometimes not the most obvious one.

But there is a harder lesson embedded in these stories too. Most of the time, papers that get desk rejected from high-tier journals do not become classics. They get revised, submitted to lower-tier journals, and published quietly. The authors who got desk rejected and eventually had landmark papers were working on landmark science. The method and the finding were genuinely extraordinary. The journals that rejected them were wrong.

For most researchers, the more useful question is not "could my paper be the next PCR story?" but "is my paper actually ready for the journal I am targeting, and if not, what would it take to get there?"

Desk rejection at a target journal is most useful as a signal when you understand what specifically triggered it. Scope mismatch is fixable: resubmit elsewhere. Novelty concerns are harder: they require either reframing or new experiments. Methods critiques are usually somewhere in between.

If you are not sure which category your desk rejection falls into, or you want to know whether your manuscript would face the same issue before you submit, a pre-submission review can answer that specifically.

See how Manusights pre-submission review works →

Got desk rejected and not sure what to do next? Read our full guide: Desk Rejected? Here's Why (And What to Do Now). Or learn how to choose the right journal so it doesn't happen again.

The Bottom Line

The takeaway from these rejections isn't that editors are wrong , it's that journal fit and manuscript framing matter as much as the science. Most of these papers found the right home once the framing matched the audience. That's a fixable problem.

Sources

• Journal editor interviews and published editorials on desk rejection criteria
• Rejection rate data from journal annual reports and editor statements
• Pre-Submission Checklist , 25-point audit before you submit
• Desk rejection reasons , the full breakdown

See also

• What to do after a desk rejection
• Desk rejection red flags

• How to avoid desk rejection