Papers that triumphed over their rejections

/ Nikolai Slavov

Most of us know of very significant foundational scientific results that were rejected by the major journals and magazines but have nonetheless stood the test of time and proven of exceptional importance to science. The goal of this post (work in progress) is to compile a list of such papers. I have limited the list below only to papers that proved to be exceptionally influential and for which there are reliable and traceable accounts of their rejections. Although the discoveries described by most of these rejected papers have been awarded the Nobel Prize, this has not been a criterion in compiling this list nor will it be as I expand it. Suggestions are most welcomed!

Bose–Einstein statistics and condensate, 1924

Bose, S (1924). Plancks Gesetz und Lichtquantenhypothese. Z. Physik 26: 178. doi:10.1007/BF01327326

Late in 1923 [Bose] submitted a paper to the subject to the Philosophical magazine. Six months later the editors of the magazine informed him that (regrettably) the referee’s reports on his paper were negative. Undeterred, he sent the rejected manuscript to Einstein …

[Bose, S., & Wali, KC., 2009, page 523]

The weak interaction (beta decay), 1933

Fermi, E (1934). An attempt of a theory of beta radiation. Z. phys, 88(161), 10.

Nature Editors: It contained speculations too remote from reality to be of interest to the reader

[Rajasekaran, 2014, page 20], Wikipedia

The Krebs cycle, 1937

Krebs, H, Johnson, WA (1937) The role of citric acid in intermediate metabolism in animal tissues. Enzymologia, 4, 148-156.

Hans Krebs: The paper was returned [from Nature] to me five days later accompanied by a letter of rejection written in the formal style of those days. This was the first time in my career, after having published more than fifty papers, that I had rejection or semi-rejection

[Krebs, 1981, page 98]

A year before Enzymologia published Kreb’s work, Nature published a welcome for Enzymologia that is remarkably relevant to our current concerns!

Laser, 1960

Maiman TH (1960). Stimulated Optical Radiation in Ruby. Nature 187: 493–494.

Charles H. Townes: He [Theodore Maiman] promptly submitted a short report of the work [report of the first laser] to the journal Physical Review Letters, but the editors turned it down.

[Townes, 2003]

The Higgs model, 1966

Higgs, PW (1966). Spontaneous symmetry breakdown without massless bosons. Physical Review, 145(4), 1156.

Peter Higgs: Higgs wrote a second short paper describing what came to be called “the Higgs model” and submitted it to Physics Letters, but it was rejected on the grounds that it did not warrant rapid publication.

[Higgs, 2013]

FT NMR, 1966

Ernst, RR, Anderson WA (1966) Application of Fourier transform spectroscopy to magnetic resonance. Review of Scientific Instruments, 37, 93-102.

Richard Ernst: The paper that described our achievements [awarded the 1991 Nobel Prize in Chemistry] was rejected twice by the Journal of Chemical Physics to be finally accepted and published in the Review of Scientific Instruments.

[Ernst, 1991]

Endosymbiotic theory, 1967

Sagan/Margulis, L. (1967). On the origin of mitosing cells. Journal of Theoretical Biology 14 (3): 225–274. PMID 11541392

Lynn Margulis: In 1966, I wrote a paper on symbiogenesis called “The Origin of Mitosing [Eukaryotic] Cells,” dealing with the origin of all cells except bacteria. (The origin of bacterial cells is the origin of life itself.) The paper was rejected by about fifteen scientific journals, because it was flawed; also, it was too new and nobody could evaluate it. Finally, James F. Danielli, the editor of The Journal of Theoretical Biology, accepted it and encouraged me. At the time, I was an absolute nobody, and, what was unheard of, this paper received eight hundred reprint requests.

[Brockman, 1995], Wikipedia

Magnetic Resonance Imaging (MRI), 1973

Lauterbur, PC (1973). Image formation by induced local interactions: examples employing nuclear magnetic resonance. Nature, 242(5394), 190-191.

Paul Lauterbur: You could write the entire history of science in the last 50 years in terms of papers rejected by Science or Nature.

[Wade, 2003], Wikipedia

The Cell Division Cycle, 1974

Hartwell LH, Culotti J, Pringle JR, Reid BJ (1974) Genetic control of the cell division cycle in yeast. Science 183:46–51.

John Pringle: Hartwell et al. (1974) was rejected without review by Nature, leaving a bad taste that has lasted…

[Pringle, 2013]

Missing data, 1976

Rubin DB (1976) Inference and missing data. Biometrika, 63, 581-592

Molenberghs (2007) wrote: … it is fair to say that the advent of missing data methodology as a genuine field within statistics, with its proper terminology, taxonomy, notation and body of results, was initiated by Rubin’s (1976) landmark paper. DB Rubin wrote …But was this a bear to get published! It was rejected, I think twice, from both sides of JASA; also from JRSS B and I believe JRSS A. … But I did not give up even though all the comments I received were very negative; but to me, these comments were also very confused and very wrong.

[Lin, 2014]

Descriptive versus normative economic theory, 1980

Thaler, R. (1980). Toward a positive theory of consumer choice. Journal of Economic Behavior & Organization, 1(1), 39-60.

Richard Thaler: Toward a Positive Theory of Consumer Choice was rejected by six or seven major journals

[Thaler, 2015]

Quasicrystals, 1984

Shechtman, D., Blech, I., Gratias, D., & Cahn, J. W. (1984). Metallic phase with long-range orientational order and no translational symmetry. Physical Review Letters, 53(20), 1951.

Dan Shechtman: It was rejected on the grounds that it will not interest physicists

[Shechtman, 2011]

Site-directed mutagenesis, 1987

Hutchison, C.A., Phillips S., Edgell M.H., Gillam S., Jahnke P., and Smith, M. Mutagenesis at a specific position in a DNA sequence. Journal of Biological Chemistry 253, no. 18 (1978): 6551-6560.

Michael Smith: When Michael Smith submitted his first article on site-directed mutagenesis for publication in Cell, a leading academic journal, it was rejected; the editors said it was not of general interest.

[Smith, 1993, 2011]

Interpreting mass-spectra, 1994

Eng, Jimmy K., Ashley L. McCormack, and John R. Yates. “An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.” Journal of the American Society for Mass Spectrometry 5.11 (1994): 976-989.

John Yates: Fred McLafferty sent it back out to Biemann and whoever else and they rejected it again.

[Yates, 2018]

Cluster analysis and display, 1998

Eisen, MB, Spellman, PT, Brown, PO, & Botstein, D (1998). Cluster analysis and display of genome-wide expression patterns. Proceedings of the National Academy of Sciences, 95(25), 14863-14868.

David Botstein: The only thing I remember telling her [the science editor] was that it was my thought that this would someday be a citation classic, and in this case I was right

[Botstein, 2009]

Please suggest other papers that belong to this list !

References

Botstein D. (2009), Personal communication. See also Riding Out Rejection that followed up this post and interviewed David.

Brockman J. (1995), The Third Culture, New York: Touchstone, 144.

Ernst R. (1991) Biographical, http://www.nobelprize.org/

Higgs P. (2013) Biographical, http://www.nobelprize.org/, Brief History

Krebs, H. (1981), Reminiscences and Reflections, Clarendon Press, Oxford.

Lin, X., Genest, C., Banks, D. L., Scott, D. W., Molenberghs, G., & Wang, J. L. (2014). Past, present, and future of statistical science. Taylor and Francis.

Mullis, K. (1998), Dancing Naked in the Mind Field, Vintage Books, New York

Pringle, J. R. (2013). An enduring enthusiasm for academic science, but with concerns. Molecular biology of the cell, 24(21), 3281-3284.

Rajasekaran, G. (2014). Fermi and the theory of weak interactions.Resonance, 19(1), 18-44.

Bose, S., & Wali, K. C. (2009). Satyendra Nath Bose: his life and times: selected works (with commentary). World Scientific. link

Shechtman D. (2011) Nobel Lecture, http://www.nobelprize.org/

Smith, M. (2011) Science.ca

Smith, M. (1993) Biographical, http://www.nobelprize.org/

Thaler, R. H. (2015). Misbehaving: The Making of Behavioral Economics. WW Norton & Company.

Townes CH. (2003) A Century of Nature: Twenty-One Discoveries that Changed Science and the World, University of Chicago Press, Link

Wade N. (2003) American and Briton Win Nobel for Using Chemists’ Test for M.R.I.’s, The New York Times, Link

Yates, JR, The Invention of SEQUEST, SCP2018, Northeastern University

62 thoughts on “Papers that triumphed over their rejections”

  1. A few colleagues wrote to me in response to this post suggesting that journal editors failed to appreciate these foundational discoveries because perhaps the discoveries were initially not articulated clearly by the authors. I find this unlikely for two reasons:

    I have read the papers, including the ones outside of my area of expertise, and as far as I can judge the papers are as clearly written as possible. Read, for example, perhaps the most technical article, the introduction of FT NMR by Ernst and Anderson, 1966. It is brilliantly simple and crystal clear!

    Another fact supporting the claim that these papers were clearly written and the discoveries well articulated is that some of the papers, such as (Mullis and Faloona, 1987; Eisen et al., 1998), became immediately highly cited and used by the broader scientific community.

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  5. Pingback: Research papers – reviewing and being reviewed — db's Medical Rants

    • Thank you Patrícia, this NY Times article confirms that Leigh Van Valen’s paper [van Valen, L. (1973). A new evolutionary law. Evolutionary Theory, 1, 1-30] was rejected and he started a journal to publish it.

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      • Whow! This is a major concept in host-parasite (and other) co-evolutionary dynamics. Super cool that you confirmed and super cool that you are keeping this list. I shared it on twitter and it has been spreading like wild fire. Thanks for putting it together and making it available.

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    • This van Valen’s paper is undoubdtedly one of the most fascinating pieces of science published over the last century. One can freely download it at: https://dl.dropboxusercontent.com/u/18310184/about-leigh-van-valen/Piglet%20Papers/1973%20new%20evol%20law.pdf. Enjoy!
      You may also be interested in: http://leighvanvalen.com/. Incidentally, another related theme (research funding) is treated in van Valen’s (1973) RQ paper, in the Acknowledgement section: “I thank the National Science Foundation for regularly rejecting my (honest) grant applications for work on real organisms (cf. Szent-Györgyi, L972), thus forcing me into theoretical work.”
      Tony Hallam in his book “Catastrophies and lesser calamities” indicates, p. 168: “the paper was rejected by both this illustrious journals [Science and Nature].” Actually, van Valen created his own journal, Evolutionary theory, in order to publish this paper. In the justification of this journal, one can read: “Originality of work is elsewhere inversely related to its acceptability.” For sure! As far as I know, van Valen himself wrote on that point, but I cannot find where at this time.
      As the editor-in-chief of a peer-reviewed paleontological journal, namely Geobios, I can say that abusive/erroneous rejection is indeed my deepest fear. Definitely, peer-review is the worst system with the exception of all others in order to evaluate the scientific interest of a research paper…

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  9. Louis Ignarro told us that his first NO paper was rejected by nature and then published in Pnas. He said he sent a copy of the rejection letter and his Nobel prize medal to Nature once he was given the prize. 🙂

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  17. Price 1970 Nature, a foundational paper in evolutionary theory, was rejected initially by Nature. George Price and Bill Hamilton had anticipated this, and put into action a cheeky plan to get Nature to reconsider the decision. See here: http://linguafranca.mirror.theinfo.org/0007/altruist.html

    This one may be different than what you’re looking for: Joe Felsenstein developed a hugely popular piece of software (PHYLIP) for inferring evolutionary trees. It was the first widely-used software for doing this, as far as I know. It was repeatedly rejected for grant funding, before and after it was developed, despite great reviews. Felsenstein memorializes this by maintaining a “no thanks to” list in PHYLIP. See http://evol-eco.blogspot.ca/2013/05/holding-fast-to-good-idea.html

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    • Thanks Jeremy !

      Below I am including a quote from this article for the strategy used for publishing the rejected paper in Nature:

      Although Price’s equation was strikingly original, its publication, which would be Price’s first in his new field, was by no means assured. Hamilton, who had felt isolated and unappreciated while working out his theory of nepotistic altruism, was anxious to help his friend avoid a similar fate. Together they devised a clever strategy to break into Nature, one of the premier science journals. Price would submit his paper on the mathematics of natural selection first. One week later, Hamilton would submit a paper that depended on Price’s formula to re-derive his theory of inclusive fitness.

      It came as no surprise when Price’s paper was returned immediately. The editors had not seen fit to send it out for review. No less surprising, the paper by Hamilton, a well-established name, was accepted without delay. According to plan, Hamilton wrote Nature to withdraw his paper. He explained that he had made use of a “powerful new method,” and he could not in good conscience publish his results until the method he used was published. The plan went off without a hitch; Nature promptly reconsidered. Price’s “Selection and Covariance” was received on November 12, 1969, and published on August 1, 1970. Befitting its entirely original approach, the paper appeared without citations.

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  19. “What the Frog’s Eye Tells the Frog’s Brain” was rejected by everyone. As explained in Wikipedia, bribery (not money) got it published. It may be the most cited scientific paper ever.

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      • Here’s some of the details regarding the “bribe” … from …

        http://www.technologyreview.com/article/508376/in-a-frogs-eye/

        These important results were initially dismissed. “We had the utmost trouble. We were laughed off the stage, literally, at the American Physiology Society in Atlantic City, where we tried to present it,” ­Lettvin told his collaborator Luis ­Amador in 1986. The NIH even threatened to withdraw his grant if he didn’t “start behaving,” he recalled. Then he got his break. “IRE [the Institute of Radio Engineers] was after me to write a paper on electrodes,” he told Amador. “I made a trade with them—I’d write the paper on electrodes if they would publish the paper on the frog’s eye.” The editor’s response? “All right, but we want a good paper on electrodes.”

        Even after the paper was published in 1959, the findings met with considerable skepticism. One disgruntled scientist—fellow MIT researcher Walter Rosenblith—”felt we were … liars, held a meeting on perception, visual perception, and didn’t invite us,” Lettvin told ­Amador. Another colleague circumvented the snub by taking conference attendees on an unannounced visit to his lab so they could see for themselves how the experiment was done. The visiting audience was convinced, and Rosenblith soon apologized. “And that,” Lettvin concluded, “was the time that we began to be taken seriously.”

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  22. Mitchell’s chemiosmotic theory was also controversial at the time and Mitchell had great trouble to get his fellow scientists to accept it – rumours has it that he was not even welcome at conferences on bioenergetics, but I do not know of any written references to a possible rejection by a journal.

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    • Thank you Jane ! Peter Mitchell’s brilliant chemiosmotic theory did indeed encounter much resistance (there are numerous references for that) for many years. The first publication of the chemiosmotic theory that I know about appeared in Nature [Mitchell, P. (1961). Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature, 191(4784), 144-148.], and I do not know whether this or other Mitchell’s papers have been rejected by journals. This paper [Mitchell, P. (1961), Nature] was not referenced/cited much in the first 5-6 years after its publication after which its citations sharply increased. I have to research more the history of the chemiosmotic theory to find if papers were rejected by journals, which seems very likely given the resistance of the community.

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  24. Nice post Nicolai, may I call your attention to the work of Paul C. Paris and co-authors published in the International Journal of Fatigue, vol. 21 (1999) S35-S46, which gives an historical account of the publication of Paul Paris’ work on fatigue crack propagation? According to the authors, the work was rejected three times and was finaly published in Trends in Engineering of the University of Whashington. It was also rejected by the USA Federal Government and by a major aircraft producer. He may not win the Nobel prize (to my best knowledge, he is still alive), but this is the most influential work on fatigue in the second half of the XXth century and, as I jokingly state to my students, this work allows us to fly airplanes at a reasonable price (OK, it is not so reasonable, but it would be much more expensive without Paris’ discovery).

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  25. Hi,

    Nice series!
    Not sure how the Botstein paper fits in the list? contribution to PNAS is the most efficient way to scoop and screw the rest of the word in a couple of days when you’re a NAS member… and it could very well be one of these papers… BD should bring more details on what happened…

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  26. Hi Erka, the paper was rejected editorially by science magazine and then published by PNAS. Its method of data display has become among the most common, if not the most common, method for genomics data, as its citation record shows.

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  27. Oh, and there’s also one of our latest papers. I can confirm that it has been editorially rejected by both Nature and Science. What I can’t confirm is it’s groundbreaking and visionary nature… 🙂

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  30. Nikolai, I remembered an editorial in Nature about this subject some time ago: “Coping With Peer Rejection”

    Click to access 425645a.pdf

    In it they describe a Physicist (Juan Miguel Campanario) who has compiled a list of Nobel Prize winning papers that were rejected. He had a webpage listing them all and eventually published this list. It can be found here:

    Click to access JUAN-MIGUEL-CAMPANARIO-Rejecting-and-resisting-Nobel-class-discoveries-accounts-by-Nobel-Laureates.pdf

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  32. Journal of Geophysical Research when rejecting, in 1963, Lawrence Morley’s manuscript showing how magnetisation patterns in ocean crust provice evidence for plate tectonics: “Such speculation makes interesting talk at cocktail parties, but it is not the sort of thing that ought to be published under serious scientific aegis.”

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    • Just catching up on this one. In about 1950, my father was a geology doctoral candidate at Harvard. In my reply to my naive question about South America “fitting” into Africa, he replied “That idea is currently out of favor; it’s non-science.” Then, angrily he said, “We’re not allowed to discuss it!” He wasn’t mad at me, I was in the second grade; he was mad at the intellectual environment.

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      • Hi Bryan and Mark,

        Thanks for your comments. Morley’s manuscript in a sad example of milestone paper that did not triumph over its rejection. I recently wrote a post on this topic. The research did triumph, some of the early pioneers did not, at least not within their lifetimes. The scepticism towards ground-breaking, paradigm-shifting results is very healthy and to be expected and encouraged. However, I find no justification for the unwillingness to consider the data or for distorted, biased and illogical evaluation of the data supporting transformative results; these are inimical to science.

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  39. The main errs of rejection in scientific history were of course Newton’s papers that created a rift with Robert Hooke and he did not publish until Hooke’s death. But perhaps the most recent rejected paper is in 1910 by Alois Alzheimer of the eponym Alzheimer’s disease. His first paper was rejected for not being interesting enough.

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