9 The German drug maker Bayer: Florian Prinz, Thomas Schlange, and Khusru Asadullah, “Believe It or Not: How Much Can We Rely on Published Data on Potential Drug Targets?,” Nature Reviews Drug Discovery 10, no. 9 (2011): 712, doi:10.1038/nrd3439-c1.
10 When the journal Nature published: C. Glenn Begley and Lee M. Ellis, “Drug Development: Raise Standards for Preclinical Cancer Research,” Nature 483, no. 7391 (2012): 531–533, doi:10.1038/483531a.
11 In 2005, John Ioannidis published: John P. A. Ioannidis, “Why Most Published Research Findings Are False,” PLOS Medicine 2, no. 8 (2005), doi:10.1371/journal.pmed.0020124.
14 He went on to calculate: Leonard P. Freedman, Iain M. Cockburn, and Timothy S. Simcoe, “The Economics of Reproducibility in Preclinical Research,” PLOS Biology 13, no. 6 (2015): e1002165, doi:10.1371/journal.pbio.1002165.
15 Two-thirds of the senior investigators: Aaron Mobley et al., “A Survey on Data Reproducibility in Cancer Research Provides Insights into Our Limited Ability to Translate Findings from the Laboratory to the Clinic,” PLOS ONE 8, no. 5 (2013): 3–6, doi:10.1371/journal.pone.0063221.
16 The American Society for Cell Biology (ASCB): “ASCB Member Survey on Reproducibility,” ACSB, 2015, http://www.ascb.org/wp-content/uploads/2015/11/final-survey-results-without-Q11.pdf.
16 From the director’s office in Building 1: Francis S. Collins and Lawrence A. Tabak, “Policy: NIH Plans to Enhance Reproducibility,” Nature 505, no. 7485 (2014): 612–613, doi:10.1038/505612a.
18 In 2012, Jack Scannell and his colleagues: Jack W. Scannell et al., “Diagnosing the Decline in Pharmaceutical R&D Efficiency,” Nature Reviews Drug Discovery 11, no. 3 (2012): 191–200, doi:10.1038/nrd3681.
23 In 1999 and 2000, several scientists made a startling claim: Timothy R. Brazelton et al., “From Marrow to Brain: Expression of Neuronal Phenotypes in Adult Mice,” Science 290, no. 5497 (December 1, 2000): 1775–1779, http://science.sciencemag.org/content/290/5497/1775.abstract; E. Gussoni et al., “Dystrophin Expression in the Mdx Mouse Restored by Stem Cell Transplantation,” Nature 401, no. 6751 (1999): 390–394, doi:10.1038/43919.
24 In 2002, Wagers concluded with typical scientific: A. J. Wagers et al., “Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells,” Science 297, no. 5590 (2002): 2256–2259, doi:10.1126/science.1074807.
24 “Most of these studies turned out”: Sean J. Morrison, “Time to Do Something About Reproducibility,” eLife 3 (2014): 1–4, doi:10.7554/eLife.03981.
27 His solution was to write a follow-up: C. Glenn Begley, “Six Red Flags for Suspect Work,” Nature 497 (2013): 433–434, doi:10.1038/497433a.
29 In the words of the brilliant physicist: Richard P. Feynman, “Cargo Cult Science,” Caltech, 1974, http://calteches.library.caltech.edu/51/2/CargoCult.htm.
30 A natural scientist realized he could test: David Wootton, The Invention of Science: A New History of the Scientific Revolution (New York: HarperCollins, 2015).
32 “We might think of an experiment”: Martin A. Schwartz, “The Importance of Indifference in Scientific Research,” Journal of Cell Science 128, no. 15 (2015): 2745–2746, doi:10.1242/jcs.174946. Quoted with author’s permission.
35 Her former mentor Elizabeth Blackburn: Tonya L. Jacobs et al., “Intensive Meditation Training, Immune Cell Telomerase Activity, and Psychological Mediators,” Psychoneuroendocrinology 36, no. 5 (2011): 664–681, doi:10.1016/j.psyneuen.2010.09.010.
35 Steven Artandi and colleagues at Stanford University: Jae-Il Park et al., “Telomerase Modulates Wnt Signalling by Association with Target Gene Chromatin,” Nature 460, no. 7251 (2009): 66–72, doi:10.1038/nature08137.
36 Based on that observation: Margaret A. Strong et al., “Phenotypes in mTERT+/− and mTERT−/− Mice Are Due to Short Telomeres, not Telomere-Independent Functions of Telomerase Reverse Transcriptase,” Molecular and Cellular Biology 31, no. 12 (2011): 2369–2379, doi:10.1128/MCB.05312-11.
36 For example, his team discovered: Linghe Xi and Thomas R. Cech, “Inventory of Telomerase Components in Human Cells Reveals Multiple Subpopulations of hTR and hTERT,” Nucleic Acids Research 42, no. 13 (2014): 8565–8577, doi:10.1093/nar/gku560.
39 “This has been characterized as”: Stuart Firestein, Failure: Why Science Is So Successful (Oxford: Oxford University Press, 2016), 159.
41 Surveying papers from biomedical science: David Chavalarias and John P. A. Ioannidis, “Science Mapping Analysis Characterizes 235 Biases in Biomedical Research,” Journal of Clinical Epidemiology 63, no. 11 (2010): 1205–1215, doi:10.1016/j.jclinepi.2009.12.011.
41 Only many years later did they appreciate: J. A. Layton and F. S. Collins, “Policy: NIH to Balance Sex in Cell and Animal Studies,” Nature 509, no. 7500 (2014): 282–283, doi:10.1038/509282a.
43 The boys with the cash incentive: L. N. Alfano et al., “T.P.1,” Neuromuscular Disorders 24, no. 9–10 (2014): 860, doi:10.1016/j.nmd.2014.06.224.
47 They published their tale: William C. Hines et al., “Sorting Out the FACS: A Devil in the Details,” Cell Reports 6, no. 5 (2014): 779–781, doi:10.1016/j.celrep.2014.02.021.
48 “They just came to opposite conclusions”: Daniel H. Madsen and Thomas H. Bugge, “The Source of Matrix-Degrading Enzymes in Human Cancer: Problems of Research Reproducibility and Possible Solutions,” Journal of Cell Biology 209, no. 2 (2015): 195–198, doi:10.1083/jcb.201501034.
49 In the 1990s, pharmaceutical companies had spent: Lisa M. Coussens, Barbara Fingleton, and Lynn M. Matrisian, “Matrix Metalloproteinase Inhibitors and Cancer: Trials and Tribulations,” Science 295, no. 5564 (2002): 2387–2392, doi:10.1126/science.1067100.
56 His 2008 study shocked: Sean Scott et al., “Design, Power, and Interpretation of Studies in the Standard Murine Model of ALS,” Amyotrophic Lateral Sclerosis: Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 9, no. 1 (2008): 4–15, doi:10.1080/17482960701856300.
57 The results: fail, fail, fail: Steve Perrin, “Make Mouse Studies Work,” Nature 507 (2014): 423, doi:10.1038/507423a.
59 She started writing and talking: Story C. Landis et al., “A Call for Transparent Reporting to Optimize the Predictive Value of Preclinical Research,” Nature 490, no. 7419 (2012): 187–191, doi:10.1038/nature11556.
59 “This is a great concern”: “Departments of Labor, Health and Human Services, and Education, and Related Agencies Appropriations for Fiscal Year 2013,” US Government Publishing Office, https://www.gpo.gov/fdsys/pkg/CHRG-112shrg29104500/html/CHRG-112shrg29104500.htm.
60 The two acknowledged the issue: Francis S. Collins and Lawrence A. Tabak, “Policy: NIH Plans to Enhance Reproducibility,” Nature 505, no. 7485 (2014): 612–613, doi:10.1038/505612a.
60 And scientists must show: “Rigor and Reproducibility,” NIH, http://grants.nih.gov/reproducibility/index.htm.
68 In fact, they’ve developed: Jacqueline G. O’Rourke et al., “C9orf72 BAC Transgenic Mice Display Typical Pathologic Features of ALS/FTD,” Neuron 88, no. 5 (2015): 892–901, doi:10.1016/j.neuron.2015.10.027; Owen M. Peters et al., “Human C9ORF72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but not Neurodegeneration in BAC Transgenic Mice,” Neuron 88, no. 5 (2015): 902–909, doi:10.1016/j.neuron.2015.11.018.
72 Five people eventually died: Institute of Medicine (US) Committee to Review the Fialuridine (FIAU/FIAC) Clinical Trials, Review of the Fialuridine (FIAU) Clinical Trials, ed. F. J. Manning and M. Swartz (Washington, DC: National Academies Press, 1995).
72 He asked a colleague: Akira Endo, “A Historical Perspective on the Discovery of Statins,” Proceedings of the Japan Academy. Series B, Physical and Biological Sciences 86, no. 5 (2010): 484–493, doi:10.2183/pjab.86.484.
72 For instance, certain drug-toxicity tests: Thomas Hartung, “Food for Thought; Look Back in Anger—What Clinical Studies Tell Us About Preclinical Work,” Altex 30, no. 3 (2013): 275–291, doi:10.1016/j.biotechadv.2011.08.021.
74 Neurologists started calling this long string: Ulrich Dirnagl and Malcolm R. Macleod, “Stroke Research at a Road Block: The Streets from Adversity Should Be Paved with Meta-analysis and Good Laboratory Practice,” British Journal of Pharmacology 157, no. 7 (2009): 1154–1156, doi:10.1111/j.1476-5381.2009.00211.
75 It was a dramatic failure: A. Shuaib et al., “NXY-059 for the Treatment of Acute Ischemic Stroke,” New England Journal of Medicine 357, no. 6 (2007): 562–571, http://www.nejm.org/doi/full/10.1056/NEJMoa070240#t=article.
75 Macleod dissected that study: Dirnagl and Macleod, British Journal of Pharmacology (2009).
75 “It is sobering”: Malcolm R. Macleod et al., “Risk of Bias in Reports of In Vivo Research: A Focus for Improvement,” PLOS Biology 13, no. 10 (2015): 1–12, doi:10.1371/journal.pbio.1002273.
78 The biology of inflammation: Junhee Seok et al., “Genomic Responses in Mouse Models Poorly Mimic Human Inflammatory Diseases,” Proceedings of the National Academy of Sciences of the United States of America 110, no. 9 (2013): 3507–3512, doi:10.1073/pnas.1222878110.
78 “You can suppress things”: Keizo Takao and Tsuyoshi Miyakawa, “Genomic Responses in Mouse Models Greatly Mimic Human Inflammatory Diseases,” Proceedings of the National Academy of Sciences of the United States of America 112, no. 4 (January 27, 2015): 1167–1172, doi:10.1073/pnas.1401965111.
78 David Masopust at the University of Minnesota: Lalit K. Beura et al., “Normalizing the Environment Recapitulates Adult Human Immune Traits in Laboratory Mice,” Nature 532, no. 7600 (April 28, 2016): 512–516, http://dx.doi.org/10.1038/nature17655.
80 Even so, these “identical” tests: S. H. Richter et al., “Effect of Population Heterogenization on the Reproducibility of Mouse Behavior: A Multi-laboratory Study,” PLOS ONE 6, no. 1 (2011), doi:10.1371/journal.pone.0016461.
80 Even a man’s sweaty T-shirt: Robert E. Sorge et al., “Olfactory Exposure to Males, Including Men, Causes Stress and Related Analgesia in Rodents,” Nature Methods 11, no. 6 (2014): 629–632, doi:10.1038/nmeth.2935.
81 Garner goes even further in his thinking: Joseph P. Garner, “The Significance of Meaning: Why Do over 90% of Behavioral Neuroscience Results Fail to Translate to Humans, and What Can We Do to Fix It?,” ILAR Journal 55, no. 3 (2014): 438–456, doi:10.1093/ilar/ilu047.
84 And Hartung has private money: Shraddha Chakradhar, “New Company Aims to Broaden Researchers’ Access to Organoids,” Nature Medicine 22, no. 4 (April 2016): 338, http://dx.doi.org/10.1038/nm0416-338.
86 She showed me a video: Kambez H. Benam et al., “Small Airway-on-a-Chip Enables Analysis of Human Lung Inflammation and Drug Responses in Vitro,” Nature Methods 13, no. 2 (February 2016): 151–157, http://dx.doi.org/10.1038/nmeth.3697.
91 Second, it’s important to remember: Jack W. Scannell and Jim Bosley, “When Quality Beats Quantity: Decision Theory, Drug Discovery, and the Reproducibility Crisis,” PLOS ONE 11, no. 2 (2016), doi:10.1371/journal.pone.0147215.
93 The team said it had isolated: N. N. Desai et al., “Novel Human Endometrial Cell Line Promotes Blastocyst Development,” Fertility and Sterility 61, no. 4 (1994): 760–766, http://www.ncbi.nlm.nih.gov/pubmed/7512055.
93 As she described in a 2008 paper: Nina Desai et al., “Live Births in Poor Prognosis IVF Patients Using a Novel Non-contact Human Endometrial Co-culture System,” Reproductive Biomedicine Online 16, no. 6 (2008): 869–874, doi:10.1016/S1472-6483(10)60154-X.
96 Even so, more than 7,000 published studies: Jill Neimark, “Line of Attack,” Science 347, no. 6225 (2015): 938–940, doi:10.1126/science.347.6225.938.
96 A 2007 study estimated: Peyton Hughes et al., “The Costs of Using Unauthenticated, Over-Passaged Cell Lines: How Much More Data Do We Need?,” BioTechniques 43, no. 5 (2007): 575–586, doi:10.2144/000112598.
96 “Have the Marx Brothers taken over”: Roland M. Nardone, “Curbing Rampant Cross-Contamination and Misidentification of Cell Lines,” BioTechniques 45, no. 3 (2008): 221–227, doi:10.2144/000112925.
98 Their list of contaminated cell lines: Amanda Capes-Davis et al., “Check Your Cultures! A List of Cross-Contaminated or Misidentified Cell Lines,” International Journal of Cancer 127, no. 1 (2010): 1–8, doi:10.1002/ijc.25242.
99 The cells from this young woman: R. Cailleau, M. Olive, and Q. V. Cruciger, “Long-Term Human Breast Carcinoma Cell Lines of Metastatic Origin: Preliminary Characterization,” In Vitro 14, no. 11 (1978): 911–915, http://www.ncbi.nlm.nih.gov/pubmed/730202.
100 In March 2000, Ross and his colleagues: D. T. Ross et al., “Systematic Variation in Gene Expression Patterns in Human Cancer Cell Lines,” Nature Genetics 24, no. 3 (2000): 227–235, doi:10.1038/73432.
101 The NCI put up a note: “MDA-MB-435, and Its Derivation MDA-N, Are Melanoma Cell Lines, Not Breast Cancer Cell Lines,” Developmental Therapeutics Program, last updated May 8, 2015, https://dtp.cancer.gov/discovery_development/nci-60/mda-mb-435.htm.
106 For example, a study in Belgium: Caroline Piette et al., “The Dexamethasone-Induced Inhibition of Proliferation, Migration, and Invasion in Glioma Cell Lines Is Antagonized by Macrophage Migration Inhibitory Factor (MIF) and Can Be Enhanced by Specific MIF Inhibitors,” Journal of Biological Chemistry 284, no. 47 (2009): 32483–32492, doi:10.1074/jbc.M109.014589.
107 The result? Scientists continue to publish: Anja Torsvik et al., “U-251 Revisited: Genetic Drift and Phenotypic Consequences of Long-Term Cultures of Glioblastoma Cells,” Cancer Medicine 3, no. 4 (2014): 812–824, doi:10.1002/cam4.219.
107 Biologists in Uppsala, Sweden, isolated it: Elie Dolgin, “Venerable Brain-Cancer Cell Line Faces Identity Crisis,” Nature, August 31, 2016, doi:10.1038/nature.2016.20515.
107 In 2016, scientists from Sweden decided: Marie Allen et al., “Origin of the U87MG Glioma Cell Line: Good News and Bad News,” Science Translational Medicine 8, no. 354 (August 31, 2016): 354re3–354re3, http://stm.sciencemag.org/content/8/354/354re3.abstract.
109 “It basically didn’t pan out”: Jean-Pierre Gillet, Sudhir Varma, and Michael M. Gottesman, “The Clinical Relevance of Cancer Cell Lines,” Journal of the National Cancer Institute 105, no. 7 (2013): 452–458, doi:10.1093/jnci/djt007.
115 After many years of increasingly excited effort: Monya Baker, “Blame It on the Antibodies,” Nature 521 (2015): 274–275, doi:10.1038/521274a.
116 “Irisin,” discovered in 2012: Pontus Boström et al., “A PGC1-α-Dependent Myokine That Drives Brown-Fat-Like Development of White Fat and Thermogenesis,” Nature 481, no. 7382 (2012): 463–468, doi:10.1038/nature10777.
117 He published a paper: Elke Albrecht et al., “Irisin—a Myth Rather Than an Exercise-Inducible Myokine,” Scientific Reports 5 (2015): 8889, doi:10.1038/srep08889.
117 They published a follow-up paper: Mark P. Jedrychowski et al., “Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry,” Cell Metabolism 22, no. 4 (2015): 734–740, doi:10.1016/j.cmet.2015.08.001.
118 But David Rimm decided to call attention: Jennifer Bordeaux et al., “Antibody Validation,” BioTechniques 48, no. 3 (March 2010): 197–209, doi:10.2144/000113382.
120 “As a result several thousand antibodies”: “1st International Antibody Validation Forum 2014: John Mountzouris,” posted to YouTube by St John’s Laboratory Ltd., October 30, 2014, https://www.youtube.com/watch?v=tnPUujPw2yY.
122 Assuming scientists do step up: Leonard P. Freedman, Iain M. Cockburn, and Timothy S. Simcoe, “The Economics of Reproducibility in Preclinical Research,” PLOS Biology 13, no. 6 (2015): e1002165, doi:10.1371/journal.pbio.1002165.
123 But Congress did just that: “H.Con.Res.385—Expressing the Sense of the Congress That the Secretary of Health and Human Services Should Conduct or Support Research on Certain Tests to Screen for Ovarian Cancer, and Federal Health Care Programs and Group and Individual Health Plans Should Cover the Tests If Demonstrated to Be Effective, and for Other Purposes,” Congress.gov, https://www.congress.gov/bill/107th-congress/house-concurrent-resolution/385.
123 News of this putative new test: Andrew Pollack, “New Cancer Test Stirs Hope and Concern,” New York Times, February 3, 2004, http://www.nytimes.com/2004/02/03/science/new-cancer-test-stirs-hope-and-concern.html.
124 Other scientists started raising doubts as well: Mark Elwood, “Proteomic Patterns in Serum and Identification of Ovarian Cancer,” Lancet 360, no. 9327 (July 13, 2002): 170, doi:http://dx.doi.org/10.1016/S0140-6736(02)09389-3.
126 Analytical errors alone account for almost: Leonard P. Freedman, Iain M. Cockburn, and Timothy S. Simcoe, “The Economics of Reproducibility in Preclinical Research,” PLOS Biology 13, no. 6 (2015): e1002165, doi:10.1371/journal.pbio.1002165.
128 “Common Genetic Variants Account for Differences”: Richard Spielman et al., “Common Genetic Variants Account for Differences in Gene Expression Among Ethnic Groups,” Nature Genetics 39, no. 2 (2007): 226–231, doi:citeulike-article-id:1043226.
129 The researchers wrote up a short analysis: Joshua M. Akey et al., “On the Design and Analysis of Gene Expression Studies in Human Populations,” Nature Genetics 39, no. 7 (July 2007): 807–808, http://dx.doi.org/10.1038/ng0707-807.
129 These case studies became central examples: Jeffrey T. Leek et al., “Tackling the Widespread and Critical Impact of Batch Effects in High-Throughput Data,” Nature Reviews Genetics 11, no. 10 (2010): 733–739, doi:10.1038/nrg2825.
132 He says only 1.2 percent: John P. A. Ioannidis, Robert Tarone, and Joseph K. McLaughlin, “The False-Positive to False-Negative Ratio in Epidemiologic Studies,” Epidemiology 22, no. 4 (2011): 450–456, doi:10.1097/EDE.0b013e31821b506e.
133 He’s found that 70 percent: John P. A. Ioannidis et al., “The Geometric Increase in Meta-analyses from China in the Genomic Era,” PLOS ONE 8, no. 6 (June 12, 2013): e65602, http://dx.doi.org/10.1371%2Fjournal.pone.0065602.
135 As the story goes: David Salsburg, The Lady Tasting Tea: How Statistics Revolutionized Science in the Twentieth Century (New York: W. H. Freeman, 2001).
136 In the winter of 2015: Michelle Schwalbe, “Statistical Challenges in Assessing and Fostering the Reproducibility of Scientific Results: Summary of a Workshop,” National Academies Press,” 2016, doi:10.17226/21915.
138 In 2016, the American Statistical Association: Ronald L. Wasserstein and Nicole A. Lazar, “The ASA’s Statement on P-Values: Context, Process, and Purpose,” American Statistician 70, no. 2 (2016), doi:10.1080/00031305.2016.1154108.
139 In a widely read 2011 paper: Joseph P. Simmons, Leif D. Nelson, and Uri Simonsohn, “False-Positive Psychology: Undisclosed Flexibility in Data Collection and Analysis Allows Presenting Anything as Significant,” Psychological Science 22, no. 11 (2011): 1359–1366, doi:10.1177/0956797611417632.
140 In science, the equivalent practice: Norbert L. Kerr, “HARKing: Hypothesizing After the Results Are Known,” Personality and Social Psychology Review 2, no. 3 (1998): 196–217, doi:10.1207/s15327957pspr0203_4.
143 The judge in the case agreed: “AIDS Healthcare Foundation, Plaintiff, vs. United States Food and Drug Administration, et al.,” AIDS Healthcare Foundation, http://www.aidshealth.org/wp-content/uploads/2013/06/Doc-60-Order-Denying-FDAs-MSJ.pdf.
146 The results made news around the world: Open Science Collaboration, “Estimating the Reproducibility of Psychological Science,” Science 349, no. 6251 (2015): aac4716–aac4716, doi:10.1126/science.aac4716.
148 He hectors journals to publish: See his website at http://www.alltrials.net.
148 Only 8 percent of the studies: Robert M. Kaplan and Veronica L. Irvin, “Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time,” PLOS ONE 10, no. 8 (2015), doi:10.1371/journal.pone.0132382.
151 The paper has been cited: E. S. Lander et al., “Initial Sequencing and Analysis of the Human Genome,” Nature 409, no. 6822 (2001): 860–921, doi:10.1038/35057062.
152 Three months later, Salzberg and his colleagues: S. L. Salzberg et al., “Microbial Genes in the Human Genome: Lateral Transfer or Gene Loss?,” Science 292, no. 5523 (2001): 1903–1906, doi:10.1126/science.1061036.
153 Salzberg was posting his data: Bjorn Nystedt et al., “The Norway Spruce Genome Sequence and Conifer Genome Evolution,” Nature 497, no. 7451 (May 30, 2013): 579–584, http://dx.doi.org/10.1038.
156 Brian Nosek paired up with: Timothy M. Errington et al., “An Open Investigation of the Reproducibility of Cancer Biology Research,” ed. Peter Rodgers, eLife 3 (2014): e04333, doi:10.7554/eLife.04333.
159 He was senior author of one: C. L. Chaffer et al., “Normal and Neoplastic Nonstem Cells Can Spontaneously Convert to a Stem-Like State,” Proceedings of the National Academy of Sciences of the United States of America 108, no. 19 (2011): 7950–7955, doi:10.1073/pnas.1102454108.
170 “I rather hate the idea”: Francis Darwin, ed., The Life and Letters of Charles Darwin (London: D. Appleton and Co., 1898), 427. Accessed via Google Books.
171 Hearing the hoofbeats of competition: Kathleen Collins, Ryuji Kobayashi, and Carol W. Greider, “Purification of Tetrahymena Telomerase and Cloning of Genes Encoding the Two Protein Components of the Enzyme,” Cell 81, no. 5 (1995): 677–686, doi:10.1016/0092-8674(95)90529-4.
171 Soon thereafter, Lingner and his mentor: J. Lingner and T. R. Cech, “Purification of Telomerase from Euplotes Aediculatus: Requirement of a Primer 3' Overhang,” Proceedings of the National Academy of Sciences of the United States of America 93, no. 20 (1996): 10712–10717, http://www.pnas.org/content/93/20/10712.short. Stephan, now at Stanford, came to a similar conclusion.
171 She wrote another paper: Chantal Autexier, D. X. Mason, and C. W. Greider, “Tetrahymena Proteins p80 and p95 Are Not Core Telomerase Components,” Proceedings of the National Academy of Sciences of the United States of America 98, no. 22 (2001): 12368–12373, doi:10.1073/pnas.221456398.
173 A study by the National Institutes of Health: “Biomedical Research Workforce Working Group Report,” NIH, June 14, 2012, http://acd.od.nih.gov/Biomedical_research_wgreport.pdf, p. 81.
177 On the December day in 2013: Randy Schekman, “How Journals like Nature, Cell and Science Are Damaging Science,” Guardian, December 9, 2013, http://www.theguardian.com/commentisfree/2013/dec/09/how-journals-nature-science-cell-damage-science.
179 Researchers in Japan claimed to have: Haruko Obokata et al., “Stimulus-Triggered Fate Conversion of Somatic Cells into Pluripotency,” Nature 505, no. 7485 (January 30, 2014): 641–647, http://dx.doi.org/10.1038/nature12968.
179 The paper was reportedly rejected: Gretchen Vogel and Dennis Normile, “Exclusive: Nature Reviewers Not Persuaded by Initial STAP Stem Cell Papers,” Science, September 11, 2014, http://www.sciencemag.org/news/2014/09/exclusive-nature-reviewers-not-persuaded-initial-stap-stem-cell-papers.
180 Investigators said she falsified dozens: “Case Summary: Forbes, Meredyth M.,” Office of Research Integrity, https://ori.hhs.gov/content/case-summary-forbes-meredyth-m.
180 Investigators found that he “duplicated images”: “Case Summary: Pastorino, John G.,” Office of Research Integrity, https://ori.hhs.gov/content/case-summary-pastorino-john-g.
181 Robert Weinberg at the Massachusetts Institute of Technology: “Cancer Research Retraction Is Fifth for Robert Weinberg; Fourth for His Former Student,” Retraction Watch, http://retractionwatch.com/2015/07/06/cancer-research-retraction-is-fifth-for-robert-weinberg-fourth-for-his-former-student.
182 Arturo Casadevall at Johns Hopkins University and colleague: Ferric C. Fang, R. Grant Steen, and Arturo Cadadevall, “Misconduct Accounts for the Majority of Retracted Scientific Publications,” Proceedings of the National Academy of Sciences of the United States of America 109, no. 42 (2012): 17028–17033, doi:10.1073/pnas.1220833110.
182 They were flabbergasted to find: David B. Allison et al., “Reproducibility: A Tragedy of Errors,” Nature 530 (February 3, 2016): 27–29, http://www.nature.com/news/reproducibility-a-tragedy-of-errors-1.19264.
184 The original authors were given a chance: Richard S. Spielman and Vivian G. Cheung, “Reply to ‘On the Design and Analysis of Gene Expression Studies in Human Populations,’” Nature Genetics 39, no. 7 (2007): 808–809, doi:10.1038/ng0707-808.
186 He has documented some of this behavior: Brian C. Martinson, Melissa S. Anderson, and Raymond de Vries, “Scientists Behaving Badly,” Nature 435, no. 7043 (2005): 737–738, doi:10.1038/435737a.
186 Daniele Fanelli, now at Stanford: Daniele Fanelli, “How Many Scientists Fabricate and Falsify Research? A Systematic Review and Meta-analysis of Survey Data,” PLOS ONE 4, no. 5 (2009), doi:10.1371/journal.pone.0005738.
187 “But if you feel the principles”: Brian C. Martinson et al., “The Importance of Organizational Justice in Ensuring Research Integrity,” Journal of Empirical Research on Human Research Ethics: JERHRE 5, no. 3 (2010): 67–83, doi:10.1525/jer.2010.5.3.67.
188 Martinson pointed to a paper: Paul E. Smaldino and Richard McElreath, “The Natural Selection of Bad Science,” Royal Society Open Science 3, no. 9 (September 21, 2016), http://rsos.royalsocietypublishing.org/content/3/9/160384.abstract.
190 Labor economist Paula Stephan at Georgia State University: Paula Stephan, “The Endless Frontier: Reaping What Bush Sowed?,” in The Changing Frontier: Rethinking Science and Innovation Policy, ed. Adam Jaffe and Benjamin Jones (Chicago: University of Chicago Press, 2015).
190 They found a dramatic increase: Christiaan H. Vinkers, Joeri K. Tijdink, and Willem M. Otte, “Use of Positive and Negative Words in Scientific PubMed Abstracts Between 1974 and 2014: Retrospective Analysis,” BMJ 351 (2015): h6467, doi: http://dx.doi.org/10.1136/bmj.h6467.
192 Maxim Shatsky and Richard Hall: Maxim Shatsky et al., “A Method for the Alignment of Heterogeneous Macromolecules from Electron Microscopy,” Journal of Structural Biology 166, no. 1 (2009): 67–78, doi:10.1016/j.jsb.2008.12.008.
192 “One must not underestimate”: R. Henderson, “Avoiding the Pitfalls of Single Particle Cryo-electron Microscopy: Einstein from Noise,” Proceedings of the National Academy of Sciences of the United States of America 110, no. 45 (2013): 18037–18041, doi:10.1073/pnas.1314449110.
193 But these young scientists seemed: K. T. Dolan, J. F. Pierre, and E. J. Heckler, “Revitalizing Biomedical Research: Recommendations from the Future of Research Chicago Symposium [version 1; referees: awaiting peer review],” F1000Research 5 (2016):1548, doi: 10.12688/f1000research.9080.1.
194 “Rescuing US Biomedical Research from Its Systemic Flaws”: Bruce Alberts et al., “Rescuing US Biomedical Research from Its Systemic Flaws,” Proceedings of the National Academy of Sciences of the United States of America 111, no. 16 (2014): 5773–5777, doi:10.1073/pnas.1404402111.
194 Attendees did agree, though, on one point: Bruce Alberts et al., “Opinion: Addressing Systemic Problems in the Biomedical Research Enterprise: Fig. 1,” Proceedings of the National Academy of Sciences of the United States of America 112, no. 7 (2015): 1912–1913, doi:10.1073/pnas.1500969112.
199 And that was enough to degrade: D. G. Hicks and L. Schiffhauer, “Standardized Assessment of the HER2 Status in Breast Cancer by Immunohistochemistry,” Laboratory Medicine 42, no. 8 (2011): 459–467, doi:10.1309/LMGZZ58CTS0DBGTW.
199 Two leading professional societies: M. Elizabeth H. Hammond et al., “American Society of Clinical Oncology/college of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer,” Journal of Clinical Oncology 28, no. 16 (2010): 2784–2795, doi:10.1200/JCO.2009.25.6529.
201 And it turned out that the hospital: Josep Villanueva et al., “Correcting Common Errors in Identifying Cancer-Specific Serum Peptide Signatures,” Journal of Proteome Research 4, no. 4 (2005): 1060–1072, doi:10.1021/pr050034b.
202 With that in mind: Francis S. Collins and Anna D. Barker, “Mapping the Cancer Genome,” Scientific American 296, no. 3 (March 2007): 50–57, doi:10.1038/scientificamerican0307-50.
204 In 2012, the group published: Mathew J. Garnett et al., “Systematic Identification of Genomic Markers of Drug Sensitivity in Cancer Cells,” Nature 483, no. 7391 (2012): 570–575, doi:10.1038/nature11005.
205 The Broad team published its first findings: Jordi Barretina et al., “The Cancer Cell Line Encyclopedia Enables Predictive Modelling of Anticancer Drug Sensitivity,” Nature 483, no. 7391 (2012): 603–607, doi:10.1038/nature11003.
205 The following year, they published: Benjamin Haibe-Kains et al., “Inconsistency in Large Pharmacogenomic Studies,” Nature 504, no. 7480 (2013): 389–393, doi:10.1038/nature12831.
206 Two years later the authors: Nicolas Stransky et al., “Pharmacogenomic Agreement Between Two Cancer Cell Line Data Sets,” Nature (2015): 84–87, doi:10.1038/nature15736.
206 The conflict spiraled: Zhaleh Safikhani et al., “Assessment of Pharmacogenomic Agreement,” F1000Research 5 (2016): 825, doi:10.12688/f1000research.8705.1.
207 But that third analysis also focused: Peter M. Haverty et al., “Reproducible Pharmacogenomic Profiling of Cancer Cell Line Panels,” Nature 533, no. 7603 (May 19, 2016): 333–337, http://dx.doi.org/10.1038/nature17987.
210 Sorger has been arguing: Marc Hafner et al., “Growth Rate Inhibition Metrics Correct for Confounders in Measuring Sensitivity to Cancer Drugs,” Nature Methods 13, no. 6 (2016): 521–527, doi:10.1038/nmeth.3853.
214 Barker’s glioblastoma study, called GBM Agile: “GBM AGILE,” National Biomarker Development Alliance, http://nbdabiomarkers.org/gbm-agile.
214 Researchers studying breast cancer pioneered: Malorye Allison, “Biomarker-Led Adaptive Trial Blazes a Trail in Breast Cancer,” Nature Biotechnology 28, no. 5 (2010): 383–384, doi:10.1038/nbt0510-383.
219 In one classic study: John P. A. Ioannidis, “Contradicted and Initially Stronger Effects in Highly Cited Clinical Research,” JAMA: The Journal of the American Medical Association 294, no. 2 (2005): 218–228, doi:10.1001/jama.294.2.218.
219 Years after two of the largest: Athina Tatsioni, Nikolaos G. Bonitsis, and John P. A. Ioannidis, “Persistence of Contradicted Claims in the Literature,” JAMA: The Journal of the American Medical Association 298, no. 21 (2007): 2517–2526, doi:10.1016/j.jemermed.2008.02.043.
220 “Why Most Published Research Findings Are False”: John P. A. Ioannidis, “Why Most Published Research Findings Are False,” PLOS Medicine 2, no. 8 (2005), doi:10.1371/journal.pmed.0020124.
221 “We agree with the paper’s”: Steven Goodman and Sander Greenland, “Assessing the Unreliability of the Medical Literature: A Response to ‘Why Most Published Research Findings Are False,’” PLOS Medicine 4, no. 4 (2007): 135, doi:10.1371/journal.pmed.0040168.
221 In addition to the pushback: Leah R. Jager and Jeffrey T. Leek, “An Estimate of the Science-Wise False Discovery Rate and Application to the Top Medical Literature,” Biostatistics 15, no. 1 (2014): 1–12, doi:10.1093/biostatistics/kxt007.
222 By one estimate, that corrective study triggered: Robert M. Kaplan and Veronica L. Irvin, “Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time,” PLOS ONE 10, no. 8 (2015), doi:10.1371/journal.pone.0132382.
228 He and two colleagues wrote that good: C. Glenn Begley, Alastair M. Buchan, and Ulrich Dirnagl, “Robust Research: Institutions Must Do Their Part for ility,” Nature 525, no. 7567 (2015): 25–27, doi:10.1038/525025a.
228 “If funding depended on a certified record”: Michael Rosenblatt, “An Incentive-Based Approach for Improving Data Reproducibility,” Science Translational Medicine 8, no. 336 (April 27, 2016): 336ed5, doi: 10.1126/scitranslmed.aaf5003.
229 Daniele Fanelli at METRICS has also suggested: Daniele Fanelli, “Set Up a ‘Self-Retraction’ System for Honest Errors,” Nature 531 (March 22, 2016): 415, doi:10.1038/531415a.
230 Paul Knoepfler at UC-Davis writes: The Niche (https://www.ipscell.com).
230 A British organization, the Faculty of 1000: See http://f1000research.com/channels/PRR.
231 Ahmed Alkhateeb, a postdoc at Harvard Medical School: Ahmed Alkhateeb, “Opinion: Reimagining the Paper,” Scientist, May 2, 2016, http://www.the-scientist.com/?articles.view/articleNo/46007/title/Opinion--Reimagining-the-Paper.
232 A year after the journal started posting: Mallory C. Kidwell et al., “Badges to Acknowledge Open Practices: A Simple, Low-Cost, Effective Method for Increasing Transparency,” ed. Malcolm R. Macleod, PLOS Biology 14, no. 5 (May 12, 2016): e1002456, doi:10.1371/journal.pbio.1002456.
233 The ARRIVE guidelines, for example, provide: Carol Kilkenny et al., “Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research,” PLOS Biology 8, no. 6 (January 29, 2010): e1000412, doi:10.1371/journal.pbio.1000412.
233 A survey of animal-research guidelines: Valerie C. Henderson et al., “Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments,” PLOS Medicine 10, no. 7 (2013), doi:10.1371/journal.pmed.1001489.
233 Nature, for example, requires scientists: “Enhancing Reproducibility,” Nature Methods 10, no. 5 (May 2013): 367, http://dx.doi.org/10.1038/nmeth.2471.
235 “As with every economy, you may need”: Alex John London and Jonathan Kimmelman, “Why Clinical Translation Cannot Succeed Without Failure,” eLife 4 (2015): 1–5, doi:10.7554/eLife.12844.
235 It seems extraordinarily unlikely: Daniel Sarewitz, “The Pressure to Publish Pushes Down Quality,” Nature 533, no. 7602 (2016): 147–147, doi:10.1038/533147a.