“Know then thyself, presume not God to scan;
The proper study of Mankind is Man.”[1]
Kristen Ranges recently earned her law degree from the University of Miami School of Law, and her doctorate in Environmental Science and Policy, from the University of Miami Rosenstiel School of Marine, Atmospheric, and Earth Science. Ranges’ dissertation was titled Animals Aiding Justice: The Deepwater Horizon Oil Spill and Ensuing Neurobehavioral Impacts as a Case Study for Using Animal Models in Toxic Tort Litigation – A Dissertation.[2] At first blush, Ranges would seem to be a credible interlocutor in the never-ending dispute over the role of whole animal toxicology (and in vitro toxicology) in determining human causation in tort litigation. Her dissertation title is, however, as Martin Short would say, a bit of a tell. Zebrafish become sad when exposed to oil spills, as do we all.
Ranges recently published a spin-off of her dissertation as a law review article with one of her professors. “Vermin of Proof: Arguments for the Admissibility of Animal Model Studies as Proof of Causation in Toxic Tort Litigation.”[3] Arguments for; no arguments against. We can thus understand this is an advocacy piece, which is fair enough. The paper was not designed or titled to mislead anyone into thinking it would be a consideration of arguments for and against extrapolation from (non-human) animal studies to human beings. Perhaps you will think it churlish of me to point out that animal studies will rarely be admissible as evidence. They come into consideration in legal cases only through expert witnesses’ reliance upon them. So the issue is not whether animal studies are admissible, but rather whether expert witness opinion testimony that relies solely or excessively on animal studies for purposes of inferring causation is admissible under the relevant evidentiary rules. Talking about the admissibility of animal model studies signals, if nothing else, a serious lack of familiarity with the relevant evidentiary rules.
Ranges’ law review is clearly, and without subtlety, an advocacy piece. She argues:
“However, judges, scholars, and other legal professionals are skeptical of the use of animal studies because of scientific and legal concerns, which range from interspecies disparities to prejudice of juries. These concerns are either unfounded or exaggerated. Animal model studies can be both reliable and relevant in toxic tort cases. Given the Federal Rules of Evidence, case law relevant to scientific evidence, and one of the goals of tort law-justice-judges should more readily admit these types of studies as evidence to help plaintiffs meet the burden of proof in toxic tort litigation.”[4]
For those of you who labor in this vineyard, I would suggest you read Ranges’ article and judge for yourself. What I see is a serious lack of scientific evidence for her claims, and a serious misunderstanding of the relevant law. One might, for starters, putting aside the Agency’s epistemic dilution, ask whether there are any I.A.R.C. category I (“known”) carcinogens based solely upon animal evidence. Or has the U.S. Food & Drug Administration ever approved a medication as reasonably safe and effective based upon only animal studies?
Every dog owner and lover has likely been told by a veterinarian, or the Humane Society, that we should resist their lupine entreaties and withhold chocolate, raisins, walnuts, avocados, and certain other human foods. Despite their obvious intelligence, capacity for affection, when it comes to toxicology, dogs are not people, although some people act like the less reputable varieties of dogs.
Back in 1985, in connection with Agent Orange litigation, the late Judge Jack Weinstein wrote what was correct then, and even more so today, that “laboratory animal studies are generally viewed with more suspicion than epidemiological studies, because they require making the assumption that chemicals behave similarly in different species.”[5] Judge Weinstein was no push-over for strident defense counsel or expert witnesses, but the legal consequences were nonetheless obvious to him, when he looked carefully at the animal studies plaintiffs’ expert witnesses were claiming to support their opinions. “[A]nimal studies are of so little probative value as to be inadmissible. They cannot be a predicate for an opinion under Rule 703.”[6] One of the several disconnects between the plaintiffs’ expert witnesses’ animal studies and the human diseases claimed was the disparity of dose and duration between the relied upon studies and the service men claimants. Judge Weinstein observed that when the hand waving stopped, “[t]here is no evidence that plaintiffs were exposed to the far higher concentrations involved in both animal and industrial exposure studies.”[7]
Ranges and Oakley unfairly deprecate the Supreme Court’s treatment of animal evidence in the 1997 Joiner opinion.[8] Mr. Joiner had been an electrician by a small city in Georgia, where he experienced dermal exposure, over several years, to polychlorinated biphenyls (PCB’s), a chemical found in electrical transformer coolant. He alleged that he had developed small-cell lung cancer from his occasional occupational exposure. In the district court, a careful judge excluded the plaintiffs’ expert witnesses, who relied heavily upon animal studies and who cherry picked and distorted the available epidemiology.[9] The Court of Appeals reversed, in an unsigned, non-substantive opinion that interjected an asymmetric standard of review.[10]
After granting review, the Supreme Court engaged with the substantive validity issues passed over by the intermediate appellate court. In addressing the plaintiff’s expert witnesses’s reliance upon animal studies, the Court was struck by an extrapolation from a different species, different route of administration, different dose, different duration of exposure, and different disease.[11] Joiner was an adult human whose alleged exposure to PCBs was far less than the exposure in the baby mice that received injections of PCBs in a high concentration. The mice developed alveologenic adenomas, a rare tumor that is usually benign, not malignant.[12] The Joiner Court recognized that these multiple extrapolations were a bridge to nowhere, and reversed the Court of Appeals, and reinstated the judgment of the district court. What is particular salient about the Joiner decision, and about which you will find no discussion in the law review paper by Ranges and Oakley, is how well the Joiner opinion has held up over quarter of a century that passed. Today, in the waning moments of 2023, there is still no valid, scientifically sound support for the claim that the sort of exposure Mr. Joiner had can cause small-cell lung cancer.[13]
Perhaps the most egregious lapses in scholarship occur when Ranges, a newly minted scientist, and her co-author, a full professor of law, write:
“For example, Bendectin, an antinausea medication prescribed to pregnant women, caused a slew of birth defects (hence its nickname ‘The Second Thalidomide’).49”[14]
I had to re-read this sentence many times to make sure I was not hallucinating. Ranges’ and Oakley’s statement is, of course, demonstrably false. A double whooper, at least, and a jarring deviation from the standard of scholarly care.
But their statement is footnoted you say. Here is what the cited article, footnote 40 in “Vermin of Proof,” says:
“RESULTS: The temporal trends in prevalence rates for specific birth defects examined from 1970 through 1992 did not show changes that reflected the cessation of Bendectin use over the 1980–84 period. Further, the NVP hospitalization rate doubled when Bendectin use ceased.
CONCLUSIONS: The population results of the ecological analyses complement the person-specific results of the epidemiological analyses in finding no evidence of a teratogenic effect from the use of Bendectin.”[15]
So the cited source actually says the exact opposite of what the authors assert. Apparently, students on law review at Georgetown University Law Center do not check citations for accuracy. Not only was the statement wrong in 1993, when the Supreme Court decided the famous Daubert case, it was wrong 20 years later, in 2013, when the United States Food and Drug Administration (FDA) approved Diclegis, a combination of doxylamine succinate and pyridoxine hydrochloride, the essential ingredients in Bendectin, for sale in the United States, for pregnant women experiencing nausea and vomiting.[16] The return of Bendectin to the market, although under a different name, was nothing less than a triumph of science over the will of the lawsuit industry.[17]
Channeling the likes of plaintiffs’ expert witness Carl Cranor (whom they cite liberally and credulously), Ranges and Oakley argue for a vague “weight of the evidence” (WOE) methodology, in which several inconclusive and lighter-than-air pieces of evidence somehow magically combine in cold fusion to warrant a conclusion of causation. Others have gone down this dubious path before, but these authors’ embrace of the plaintiffs’ expert witnesses’ opinion in Bendectin litigation reveals the insubstantiality and the invalidity of their method.[18] As Professor Ronald Allen put the matter:
“Given the weight of evidence in favor of Bendectin’s safety, it seems peculiar to argue for mosaic evidence [WOE] from a case in which it would have plainly been misleading.”[19]
It surely seems like a reduction ad absurdum of the proposed methodology.
One thing these authors get right is that most courts disparage and exclude expert witness opinion that relies exclusively or excessively upon animal toxicology.[20] They wrongly chastise these courts, however, for ignoring scientific opinion. In 2005, the Teratology Society issued a position paper on causation in teratology-related litigation,[21] in which the Society specifically addressed the authors’ claims:
“6. Human data are required for conclusions that there is a causal relationship between an exposure and an outcome in humans. Experimental animal data are commonly and appropriately used in establishing regulatory exposure limits and are useful in addressing biologic plausibility and mechanism questions, but are not by themselves sufficient to establish causation in a lawsuit. In vitro data may be helpful in exploring mechanisms of toxicity but are not by themselves evidence of causation.”[22]
Ranges and Oakley are flummoxed that courts exclude expert witnesses who have relied upon animal studies when regulatory agencies use such studies with abandon. The case law on the distinction between precautionary standards in regulation and causation standards in tort law is clear, and explains the difference in approach, but these authors are determined to ignore the obvious difference.[23] The Teratology Society emphasized what should be hornbook law; namely, regulatory standards for testing and warnings are not particularly germane to tort law standards for causation:
“2. The determination of causation in a lawsuit is not the same as a regulatory determination of a protective level of exposure. If a government agency has determined a regulatory exposure level for a chemical, the existence of that level is not evidence that the chemical produces toxicity in humans at that level or any other level. Regulatory levels use default assumptions that are improper in lawsuits. One such assumption is that humans will be as sensitive to the toxicity of a chemical as is the most sensitive experimental animal species. This assumption may be very useful in regulation but is not evidence that exposure to that chemical caused an adverse outcome in an individual plaintiff. Regulatory levels often incorporate uncertainty factors or margins of exposure. These factors may result in a regulatory level much lower than an exposure level shown to be harmful in any organism and are an additional reason for the lack of utility of regulatory levels in causation considerations.”[24]
The suggestion from Ranges and Oakley that the judicial treatment of reliance upon animal studies is based upon ossified, ancient precedent, prejudice, and uncritical acceptance of defense counsel’s unsupported argument is simply wrong. There are numerous discussions of the difficulty of extrapolating teratogenicity from animal data to humans,[25] and ample basis for criticism of the glib extension of rodent carcinogenicity to humans.[26]
Ranges and Oakley ignore the extensive scientific literature questioning extrapolation from high exposure rodent models to much lower exposures in humans.[27] The invalidity of extrapolation can result in both false positives and false negatives. Indeed the thalidomide case is a compelling example of the failure of animal testing. Thalidomide was tested on pregnant rats and rabbits without detecting teratogenicity; indeed most animal species do not metabolize thalidomide or exhibit teratogenicity as seen in humans. Animal models simply do not have a sufficient positive predictive value to justify a conclusion of causation in humans, even if we accept a precautionary principle recognition of such animal testing for regulatory purposes.[28]
As improvident as Ranges’ pronouncements may be, finding her message amplified by Professor Ed Cheng on his podcast series, Excited Utterances, was even more disturbing. In November 2023, Cheng interviewed Kristen Ranges in an episode of his podcast, Vermin of Proof, in which he gave Ranges a chance to reprise her complaints about the judiciary’s handling of animal evidence, without much in the way of specificity, and with some credulous cheerleading to aid and abet. In his epilogue, Cheng wondered why toxicologic evidence is disfavored when such evidence is routinely used by scientists and regulators. What Cheng misses is that regulators use toxicologic evidence for regulation, not for assessments of human causation, and that the two enterprises are quite different. The regulatory exercise goes something like asking about the stall speed of a pig. It does not matter that pigs cannot fly; we skip that fact and press on to ask what the pig’s take off and stall speeds are.
Seventy years ago, no less than Sir Austin Bradford Hill, observed that:
“We may subject mice, or other laboratory animals, to such an atmosphere of tobacco smoke that they can — like the old man in the fairy story — neither sleep nor slumber; they can neither breed nor eat. And lung cancers may or may not develop to a significant degree. What then? We may have thus strengthened the evidence, we may even have narrowed the search, but we must, I believe, invariably return to man for the final proof or proofs.”[29]
[1] Alexander Pope, “An Essay on Man” (1733), in Robin Sowerby, ed., Alexander Pope: Selected Poetry and Prose at 153 (1988).
[2] Kristen Ranges, Animals Aiding Justice: The Deepwater Horizon Oil Spill and Ensuing Neurobehavioral Impacts as a Case Study for Using Animal Models in Toxic Tort Litigation – A Dissertation (2023).
[3] Kristen Ranges & Jessica Owley, “Vermin of Proof: Arguments for the Admissibility of Animal Model Studies as Proof of Causation in Toxic Tort Litigation,” 34 Georgetown Envt’l L. Rev. 303 (2022) [Vermin]
[4] Vermin at 303.
[5] In re Agent Orange Prod. Liab. Litig., 611 F. Supp. 1223, 1241 (E.D.N.Y. 1985), aff’d, 818 F.2d 187 (2d Cir. 1987), cert. denied, 487 U.S. 1234 (1988).
[6] Id.
[7] Id.
[8] General Elec. Co. v. Joiner, 522 U.S. 136, 144 (1997) [Joiner]
[9] Joiner v. General Electric Co., 864 F. Supp. 1310 (N.D. Ga. 1994).
[10] Joiner v. General Electric Co., 134 F.3d 1457 (11th Cir. 1998) (per curiam).
[11] Joiner, 522 U.S. at 144-45.
[12] See Leonid Roshkovan, Jeffrey C. Thompson, Sharyn I. Katz, Charuhas Deshpande, Taylor Jenkins, Anna K. Nowak, Rosyln Francis, Carole Dennie, Dominique Fabre, Sunil Singhal, and Maya Galperin-Aizenberg, “Alveolar adenoma of the lung: multidisciplinary case discussion and review of the literature,” 12 J. Thoracic Dis. 6847 (2020).
[13] See “How Have Important Rule 702 Holdings Held Up With Time?” (Mar. 20, 2015); “The Joiner Finale” (Mar. 23, 2015).
[14] Vermain at 312.
[15] Jeffrey S Kutcher, Arnold Engle, Jacqueline Firth & Steven H. Lamm, “Bendectin and Birth Defects II: Ecological Analyses, 67 Birth Defects Research Part A: Clinical and Molecular Teratology 88, 88 (2003).
[16] See FDA News Release, “FDA approves Diclegis for pregnant women experiencing nausea and vomiting,” (April 8, 2013).
[17] See Gideon Koren, “The Return to the USA of the Doxylamine-Pyridoxine Delayed Release Combination (Diclegis®) for Morning Sickness — A New Morning for American Women,” 20 J. Popul. Ther. Clin. Pharmacol. e161 (2013).
[18] Michael D. Green, “Pessimism About Milward,” 3 Wake Forest J. Law & Policy41, 62-63 (2013); Susan Haack, “Irreconcilable Differences? The Troubled Marriage of Science and Law,” 72 Law & Contemporary Problems 1, 17 (2009); Susan Haack, “Proving Causation: The Holism of Warrant and the Atomism of Daubertm” 4 J. Health & Biomedical Law 273, 274-78 (2008).
[19] Ronald J. Allen & Esfand Nafisi, “Daubert and its Discontents,” 76 Brooklyn L. Rev. 132, 148 (2010).
[20] See In re Zoloft (Sertraline Hydrochloride) Prods. Liab. Litig., 26 F. Supp. 3d 466, 475 (E.D. Pa. 2014) (noting that “causation opinions based primarily upon in vitro and live animal studies are unreliable and do not meet the Daubert standard.”), aff’d, 858 F.3d 787 (3rd Cir. 2017); Chapman v. Procter & Gamble Distrib., LLC, 766 F.3d 1296, 1308 (11th Cir. 2014) (affirming exclusion of testimony based on “secondary methodologies,” including animal studies, which offer “insufficient proof of general causation.”); The Sugar Ass’n v. McNeil-PPC, Inc., 2008 WL 11338092, *3 (C.D. Calif. July 21, 2008) (finding that plaintiffs’ expert witnesses, including Dr. Abou-Donia, failed to provide the requisite analytical support for the extrapolation of their Five Opinions from rats to humans”); In re Silicone Gel Breast Implants Prods. Liab. Litig., 318 F. Supp. 2d 879, 891 (C.D. Cal. 2004) (observing that failure to compare similarities and differences across animals and humans could lead to the exclusion of opinion evidence); Cagle v. The Cooper Companies, 318 F. Supp. 2d 879, 891 (C.D. Calif. 2004) (citing Joiner, for observation that animal studies are not generally admissible when contrary epidemiologic studies are available; and detailing significant disadvantages in relying upon animal studies, such as (1) differences in absorption, distribution, and metabolism; (2) the unrealistic, non-physiological exposures used in animal studies; and (3) the use of unverified assumptions about dose-response); Wills v. Amerada Hess Corp., No. 98 CIV. 7126(RPP), 2002 WL 140542, at *12 (S.D.N.Y. Jan. 31, 2002) (faulting expert’s reliance on animal studies because there was no evidence plaintiff had injected suspected carcinogen in same manner as studied animals, or at same dosage levels), aff’d, 379 F.3d 32 (2nd Cir. 2004) (Sotomayor, J.); Bourne v. E.I. du Pont de Nemours & Co., 189 F. Supp. 2d 482, 501 (S.D. W.Va. 2002) (benlate and birth defects), aff’d, 85 F. App’x 964 (4th Cir.), cert. denied, 543 U.S. 917 (2004); Magistrini v. One Hour Martinizing Dry Cleaning noted that “[a]nimal bioassays are of limited use in determining whether a particular chemical causes a particular disease, or type of cancer, in humans.”190 180 F. Supp. 2d 584, 593 (D.N.J. 2002); Soutiere v. BetzDearborn, Inc., No. 2:99-CV-299, 2002 WL 34381147, at *4 (D. Vt. July 24, 2002) (holding expert’s evidence inadmissible when “[a]t best there are animal studies that suggest a link between massive doses of [the substance in question] and the development of certain kinds of cancers, such that [the substance in question] is listed as a ‘suspected’ or ‘probable’ human carcinogen”); Glastetter v. Novartis Pharms. Corp., 252 F.3d 986, 991 (8th Cir. 2001); Hollander v. Sandoz Pharm. Corp., 95 F. Supp. 2d 1230, 1238 (W.D. Okla. 2000), aff’d, 289 F.3d 1193, 1209 (10th Cir. 2002) (rejecting the relevance of animal studies to causation arguments in the circumstances of the case); Allison v. McGhan Medical Corp., 184 F.3d 1300, 1313–14 (11th Cir.1999); Raynor v. Merrell Pharrns. Inc., 104 F.3d 1371, 1375-1377 (D.C. Cir.1997) (observing that animal studies are unreliable, especially when “sound epidemiological studies produce opposite results from non-epidemiological ones, the rate of error of the latter is likely to be quite high”); Lust v. Merrell Dow Pharms., Inc., 89 F.3d 594, 598 (9th Cir.1996); Barrett v. Atlantic Richfield Co., 95 F.3d 375 (5th Cir. 1996) (extrapolation from a rat study was speculation); Nat’l Bank of Comm. v. Dow Chem. Co., 965 F. Supp. 1490, 1527 (E.D. Ark. 1996) (“because of the difference in animal species, the methods and routes of administration of the suspect chemical agent, maternal metabolisms and other factors, animal studies, taken alone, are unreliable predictors of causation in humans”), aff’d, 133 F.3d 1132 (8th Cir. 1998); Hall v. Baxter Healthcare Corp., 947 F. Supp. 1387, 1410-11 (D. Or. 1996) (with the help of court-appointed technical advisors, observing that animal studies taken alone fail to predict human disease reliably); Daubert v. Merrell Dow Pharrns., Inc., 43 F.3d 1311, 1322 (9th Cir. 1995) (on remand from Supreme Court with directions to apply an epistemic standard derived from Rule 702 itself); Sorensen v. Shaklee Corp., 31 F.3d 638, 650 (8th Cir.1994) (affirming exclusion of expert witness opinions based upon animal mutagenicity data not germane to the claimed harm); Elkins v. Richardson-Merrell, Inc., 8 F.3d 1068, 1073 (6th Cir. 1993);Wade-Greaux v. Whitehall Labs., Inc., 874 F. Supp. 1441, 1482 (D.V.1. 1994), aff’d, 46 F.3d 1120 (3d Cir. 1994) (per curiam); Renaud v. Martin Marietta Corp., Inc., 972 F.2d 304, 307 (10th Cir.1992) (“The etiological evidence proffered by the plaintiff was not sufficiently reliable, being drawn from tests on non-human subjects without confirmatory epidemiological data.”) (“Dr. Jackson performed no calculations to determine whether the dose or route of administration of antidepressants to rats and monkeys in the papers that she cited in her report was equivalent to or substantially similar to human beings taking prescribed doses of Prozac.”); Bell v. Swift Adhesives, Inc., 804 F. Supp. 1577, 1579–81 (S.D. Ga. 1992) (excluding expert opinion of Dr. Janette Sherman, who opined that methylene chloride caused liver cancer, based largely upon on animal studies); Conde v. Velsicol Chem. Corp., 804 F. Supp. 972, 1025-26 (S.D. Ohio 1992) (noting that epidemiology is “the primary generally accepted methodology for demonstrating a causal relation between a chemical compound and a set of symptoms or a disease”), aff’d, 24 F.3d 809 (6th Cir. 1994); Turpin v. Merrell Dow Pharm., Inc., 959 F.2d 1349, 1360-61 (6th Cir. 1992) (“The analytical gap between the [animal study] evidence presented and the inferences to be drawn on the ultimate issue of human birth defects is too wide. Under such circumstances, a jury should not be asked to speculate on the issue of causation.”); Brock v. Merrell Dow Pharm., 874F.2d 307, 313 (5th Cir. 1989) (noting the “very limited usefulness of animal studies when confronted with questions of toxicity”); Richardson v. Richardson-Merrell, Inc., 857 F. 2d 823, 830 (D.C. Cir. 1988) (“Positive results from in vitro studies may provide a clue signaling the need for further research, but alone do not provide a satisfactory basis for opining about causation in the human context.”); Lynch v. Merrell-Nat‘l Labs., 830 F.2d 1190, 1194 (1st Cir. 1987) (“Studies of this sort [animal studies], singly or in combination, do not have the capability of proving causation in human beings in the absence of any confirmatory epidemiological data.”). See also Merrell Dow Pharrns., Inc. v. Havner, 953 S.W.2d 706, 730 (Tex. 1997); DePyper v. Navarro, No. 83-303467-NM, 1995 WL 788828, at *34 (Mich. Cir. Ct. Nov. 27, 1995), aff’d, No. 191949, 1998 WL 1988927 (Mich. Ct. App. Nov. 6, 1998); Nelson v. American Sterilizer Co., 566 N.W.2d 671 (Mich. Ct. App. 1997)(high-dose animal studies not reliable). But see Ambrosini v. Labarraque, 101 F.3d 129, 137-140 (D.C. Cir.1996); Dyson v. Winfield, 113 F. Supp. 2d 44, 50-51 (D.D.C. 2000).
[21] Teratology Society Public Affairs Committee, “Position Paper Causation in Teratology-Related Litigation,” 73 Birth Defects Research (Part A) 421 (2005) [Teratology Position Paper]
[22] Id. at 423.
[23] See “Improper Reliance Upon Regulatory Risk Assessments in Civil Litigation” (Mar. 19, 2023) (collecting cases).
[24] Teratology Position Paper at 422-423.
[25] See, e.g., Gideon Koren, Anne Pastuszak & Shinya Ito, “Drugs in Pregnancy,” 338 New England J. Med. 1128, 1131 (1998); Louis Lasagna, “Predicting Human Drug Safety from Animal Studies: Current Issues,” 12 J. Toxicological Sci. 439, 442-43 (1987).
[26] Bruce N. Ames & Lois S. Gold, Too Many Rodent Carcinogens: Mitogenesis Increases Mutagenesis, 249 Science 970, 970 (1990) (noting that chronic irritation induced by many chemicals at high exposures is itself a cause of cancer in rodent models); Bruce N. Ames & Lois Swirsky Gold, “Environmental Pollution and Cancer: Some Misconceptions,” in Jay H. Lehr, ed., Rational Readings on Environmental Concerns 151, 153 (1992); Mary Eubanks, “The Danger of Extrapolation: Humans and Rodents Differ in Response to PCBs,” 112 Envt’l Health Persps. A113 (2004)
[27] Andrea Gawrylewski, “The Trouble with Animal Models: Why did human trials fail?” 21 The Scientist 44 (2007); Michael B. Bracken, “Why animal studies are often poor predictors of human reactions to exposure,” 101 J. Roy. Soc. Med. 120 (2008); Fiona Godlee, “How predictive and productive is animal research?” 3348 Brit. Med. J. g3719 (2014); John P. A. Ioannidis, “Extrapolating from Animals to Humans,” 4 Science Translational Med. 15 (2012); Pandora Pound & Michael Bracken, “Is animal research sufficiently evidence based to be a cornerstone of biomedical research?” 348 Brit. Med. J. g3387 (2014); Pandora Pound, Shah Ebrahim, Peter Sandercock, Michael B Bracken, and Ian Roberts, “Where is the evidence that animal research benefits humans?” 328 Brit. Med. J. 514 (2004) (writing on behalf of the Reviewing Animal Trials Systematically (RATS) Group).
[28] See Ray Greek, Niall Shanks, and Mark J. Rice, “The History and Implications of Testing Thalidomide on Animals,” 11 J. Philosophy, Sci. & Law 1, 19 (2011).
[29] Austin Bradford Hill, “Observation and Experiment,” 248 New Engl. J. Med. 995, 999 (1953).
