In 2009, the UK House of Commons Science and Technology Committee (STC) conducted an ‘evidence check’ on homeopathy to evaluate evidence for its effectiveness. In common with the wider literature critical of homeopathy, the STC report seems to endorse many of the strong claims that are made about its implausibility. In contrast with the critical literature, however, the STC report explicitly does not place any weight on implausibility in its evaluation. I use the contrasting positions of the STC and the wider critical literature to examine the ‘implausibility arguments’ against homeopathy and the place of such arguments within evidence-based medicine (EBM). I argue that the STC report undervalues its strong claims about the mechanistic plausibility of homeopathy because it relies on a misunderstanding about the role of mechanistic evidence within EBM. This is not a conclusion for a revision of the role mechanistic evidence plays within EBM, however. It is a conclusion about the inconsistency of the STC report’s position towards implausibility arguments, given the evidential claims they endorse and the atypical situation that homeopathy presents. It provides a further example of the general point that mechanistic reasoning should not be seen as providing categorically lower quality evidence. Lancet, concluding that there was no evidence that homeopathic treatments were better than placebo. This meta-analysis became a focal point for growing criticism of homeopathy and attracted many responses in the academic literature  not only out of line with scientific facts but also directly opposed to them. If homeopathy is correct, much of physics, chemistry, and pharmacology must be incorrect.… We think that a belief in homeopathy exceeds the tolerance of an open mind. We should start from the premise that homeopathy cannot work. It is a cure that does not make sense in the light of science.… [H]omeopathy cannot possibly work because it has no scientifically plausible grounds. Those who claim that homeopathy is effective have enormous unexplained mysteries, and answering those mysteries would appear to require massive revision of standard chemistry and physiology…. [T]he balance is heavily against homeopathy. We understand that it cannot work through any mechanism that is in accordance with the known laws of nature. These are strong claims. The strongest suggest that homeopathy ‘cannot’ work. Other statements make a slightly weaker claim by allowing the possibility that the quasi-pharmacological component of homeopathy is effective, but balance this concession against the substantial revisions in our understanding of the sciences that they claim would be necessary as a result.Today, echoing Forbes, similar critical emphasis is placed on the idea that a substance can get more potent as it is diluted. Timothy Caulfield and Suzanne Debow conducted a systematic review of how homeopathy was represented in conventional and alternative medicine journals. They found that within conventional medical journals, nine out of ten review articles ‘begin with a statement that questions the scientific plausibility of homeopathy’ . StatemeIt is very implausible that there could be a mechanism by which the quasi-pharmacological component of homeopathic treatment is effective.If it is very implausible that there could be a mechanism for how some component of a treatment is effective, then it is very unlikely that component is effective.Therefore,It is very unlikely that the quasi-pharmacological component of homeopathic treatments is effective.The critical literature contains many statements like those quoted above that demonstrate a commitment to the claims made in premise (1) and the conclusion. It is harder to find a clear statement of premise (2). The move from (1) to (3) is not spelt out in the literature.The crucial move in this contemporary critical literature is to take the implausibility of a mechanism by which the quasi-pharmacological component of homeopathic treatments could be effective as evidence that it is not effective. This idea is at the heart of what I call an ‘implausibility argument against homeopathy’, which goes as follows:There is some ambiguity in the statements quoted above around whether they are statements of implausibility or would be better characterised as statements of impossibility. Those claiming that homeopathy ‘cannot’ work are easily read as statements of impossibility. If ‘very implausible’ is changed to ‘impossible’ in the argument above, then it remains valid. However, that also significantly raises the evidential burden. The argument becomes invalid if one tries to use (1) and (2) as they stand to draw the conclusion that it is impossible that the quasi-pharmacological component of homeopathic treatment is effective. Equally, premise (2) becomes false if it is modified to allow one to move from a very implausible mechanism to actual ineffectiveness, rather than to very implausible effectiveness.cannot be effective simply because we believe that it should not be effective. We are not infallible and the implausibility argument does not claim that we are.Reconstructing the argument also requires some sensitivity to the status of the texts these quotes come from. The strong statements of impossibility are typically found in editorials and commentary articles, so it is important to acknowledge the rhetorical force that a claim of this strength possesses, and therefore, to recognise the role that this kind of discourse plays in attempts to close the debate by exaggerating the evidence. I suggest that the most charitable construction of the argument is to put it in terms of implausibility rather than impossibility. Whether the argument is spelt out in terms of impossibility or implausibility, it is important that we should not be able to infer that the quasi-pharmacological component of homeopathy There are two further points to note about this implausibility argument. First, the argument is based on inferences from theory rather than from comparisons between groups of individuals; hence, the suggestions that homeopathy is in conflict with ‘known laws of nature’, ‘standard chemistry and physiology’, or ‘much of physics, chemistry and pharmacology’ . The inference is from basic theoretical knowledge that it is implausible that there could be a mechanism by which the quasi-pharmacological component of homeopathy works to the conclusion that it likely does not work.may be effective because one is in a position of mechanistic ignorance. That is to say, the conclusion is not that one does not know or cannot be sure that the quasi-pharmacological component is effective because we lack a full mechanistic understanding of it. It is an argument for the stronger conclusion that mechanistic implausibility provides good evidence that the quasi-pharmacological component of the treatment is very unlikely to be effective. The claim is that mechanistic implausibility constitutes evidence for the likely absence of effectiveness.Second, it is easy to misunderstand the inference. The arguments made in the wider critical literature about homeopathy do not conclude that the quasi-pharmacological component The STC endorse premise (1). In common with the wider critical literature, the STC report endorses similarly strong claims about the implausibility of a mechanism by which the quasi-pharmacological component of homeopathic treatment could be effective. The key statements in the report occur in paragraphs 48–62, in a substantial section titled ‘Scientific Plausibility for a Mode of Action’. In this section of the report, two of the theoretical principles behind homeopathic treatment that inform the production of homeopathic medicine are scrutinised. The first of these is the similarity principle, which is the idea that ‘like-cures-like’, noted above. The second is the notion of potentisation, also noted above, and in particular, the high level of dilution of the potentised liquids that are used to produce homeopathic medicines.The similarity principle and the use of high dilutions are both regarded as scientifically implausible. For example, the similarity principle is claimed to be ‘theoretically weak’: ‘It fails to provide a credible physiological mode of action for homeopathic products’ [To support these claims, the report cites evidence submitted to the STC (either in writing or during their panel sessions). For example, they quote favourably the view of David Colqhoun, a professor of pharmacology and prominent critic of homeopathy: ‘If homeopathy worked, the whole of chemistry and physics would have to be overturned’ . The repAs noted above, strong statements of implausibility play an important rhetorical role by allowing critics of homeopathy to close down the debate about its effectiveness as settled. This strategy is also apparent in the STC report when it questions whether it is appropriate to invest in further research ‘exploring theories that are not scientifically plausible’. Moreover the STC heard evidence from the Government Chief Scientific Adviser, who claimed that there is no evidence base for homeopathy. This led to the STC further recommending that the UK Government and Department of Health jointly discuss whether there is ‘any merit in research funding being directed towards the claimed modes of action of homeopathy’ [I claim, therefore, that the STC report holds the same position as the wider critical literature in relation to the key evidential premise (1) in the implausibility argument above. The report endorses the view that it is very implausible that there could be a mechanism by which the quasi-pharmacological component is effective.Unlike the wider critical literature, however, the STC reject the use of premise (1) to make an argument against the effectiveness of the quasi-pharmacological component of homeopathy. The STC report does not appear to endorse the conclusion of the implausibility argument. Instead, they hold the view that the implausibility of a mechanism by which the quasi-pharmacological component could be effective counts for very little in the assessment of whether it is effective. To illustrate, the STC goes on to de-emphasise the role that plausibility considerations play in their assessment of the evidence for the effectiveness of homeopathy: ‘While we comment on explanations for how homeopathy works, it is not a key part of our Evidence Check’ [In sum, the STC agree with the wider critical literature that the effectiveness of the quasi-pharmacological component of homeopathy is very implausible. The key difference between the STC report and wider critical literature is that the STC report does not value and subsequently use this evidence in their assessment of the effectiveness of homeopathy. Given the rhetorical force of the implausibility argument to close down the debate, this deliberate discounting of such evidence is particularly noteworthy. The STC defend their rejection of plausibility considerations in their evaluation on the basis that evidence of plausibility is not necessary for the effectiveness of the quasi-pharmacological component of homeopathic treatment.The STC report is correct that lack of evidence of plausibility should not be taken to rule out the effectiveness of the quasi-pharmacological component. However, stating that fact, as they do in the quotations above, is not a denial of premise (2); moreover, it does not engage with the kind of claim being made in premise (1). Although true, it does not provide a good reason to reject the implausibility argument. The difference between the implausibility argument and the STC’s rejection of plausibility considerations is similar to the difference between ‘evidence of absence’ and ‘absence of evidence’.there could be a mechanism by which the quasi-pharmacological component of homeopathic treatment is effective. Premise (2) makes a link between the very implausible possibility of a mechanism and the likely ineffectiveness of that component of a treatment. The implausibility of there being any mechanism by which the quasi-pharmacological component could be effective is taken to provide good evidence that the component likely is not effective. The implausibility argument therefore aims to establish evidence of absence.To reiterate the premises of the implausibility argument, premise (1) is that it is very implausible that This is a separate issue from whether there might be a mechanism that we do not know or understand, and it is unrelated to the fact that one does not need a treatment to seem plausible in order to know that it works. The STC report is right to state that absence of evidence of plausibility is poor grounds to deny the effectiveness of the quasi-pharmacological component of homeopathy. The STC are wrong, however, to say that this therefore provides a good reason to dismiss the implausibility argument. The implausibility argument is a much stronger argument based on the notion that there is unlikely to be any possible mechanism by which the quasi-pharmacological component could be effective.stronger.The first problem facing the STC’s position, therefore, is that the reasons they provide for rejecting the relevance of plausibility considerations in general are not good reasons for rejecting the implausibility argument. Additionally, there is also a second, more interesting, problem for the STC position. Not only has the STC report misunderstood the implausibility argument, but it has also undervalued the role of mechanistic reasoning in the assessment of homeopathy. I argue that the STC have missed the opportunity to make the argument in their report whether a treatment works—its efficacy—than how it works’ [The STC do not value implausibility as evidence. This can be further seen in the way the report deploys a distinction between whether and how a treatment works. The report states: ‘It is more important to know Furthermore, elsewhere in the STC report, there are clear expectations for what kind of evidence is most important and should count in the assessment of the effectiveness of the quasi-pharmacological component of homeopathy. Namely, the best evidence comes from the pooled results of randomised trials using a placebo control. As the report states, ‘In clinical research, it is widely accepted that RCTs are the best way to evaluate the efficacy of different treatments and distinguish them from placebos…. We consider that conclusions about the evidence on the efficacy of homeopathy should be derived from well designed and rigorous randomised controlled trials (RCTs)’ [This position is, of course, exactly what one would expect from a commitment to EBM. EBM provides the framework for the report’s statements about the ‘wide acceptance’ of randomised trials as providing good evidence of treatment effects. Indeed, a placebo-controlled randomised trial is perfectly equipped to assess the effectiveness of the quasi-pharmacological component of homeopathic treatment. Although the STC report does not cite EBM textbooks or any of the current evidence rating systems  with a clinical outcome ’ . This acThe implausibility argument has a different form, however. Reasoning about implausibility involves an inference from the absence of a mechanism to the absence of an effect. The inference is not from the existence of a known mechanism but from the implausibility that there could be a mechanism, and not to some effect but to the implausibility of there being any effect. The implausibility argument is also more specific, in the sense that it is not the effect of a treatment that is in question but the effect due to one particular feature of the treatment: the quasi-pharmacological component. The implausibility argument leaves open the possibility that there are other mechanisms by which homeopathic treatment is effective (one obvious example being expectation effects).This account also helps clarify a crucial point made above, namely, that the implausibility argument is not an argument from ignorance: the inference is based on the claimed absence, not our ignorance, of a mechanism. Indeed, as shown above, the STC report and other critics of homeopathy claim that there is a significant level of empirical support for the implausibility of there being a mechanism by which the quasi-pharmacological component of homeopathic treatment could be effective.The implausibility argument fits the broad pattern of mechanistic reasoning in so far as it is an inference from a claim about mechanisms to a claim about effects. But it is also clearly different from other examples because it is about the lack of any mechanism and the lack of an effect. Howick suggests that his criteria for judging the quality of mechanistic reasoning should apply to both acceptance and rejection of an effect . Here thBritish Medical Journal’s Christmas edition. Like the best articles in the Christmas editions, it makes a serious point with an absurd example. Leibovici examined the records of 3393 patients who were treated for bloodstream infections between 1990 and 1996 and randomised into two groups in the year 2000, one of which was chosen to be prayed for. Leibovici found that while intercessory prayer had no significant effect on mortality, the intervention group showed a small effect on secondary outcome measures: they had a statistically significant shorter duration of fever and a shorter stay in hospital (these two outcomes are not entirely independent).Leonard Leibovici reported results from a randomised trial investigating the effect of remote, retroactive, intercessory prayer on patients who suffered from bloodstream infections . The artPutting aside independent methodological reasons to reject the results of this study , an obviThis result has strong parallels with what critics claim about the quasi-pharmacological component of homeopathy. Analogously to ruling out Leibovici’s hypothesis on the basis of general knowledge about causality, we also have general and fundamental background knowledge of physics, chemistry, and biology—so the critics argue—that rules out the possibility of there being a mechanism by which the quasi-pharmacological component of homeopathy could be effective. If we take remote retroactive prayer as the component of interest, we can run through the implausibility argument as set out in the above subsection, ‘Implausibility in the Critical Literature about Homeopathy’, unchanged. Leibovici’s hypothesis and the effectiveness of the quasi-pharmacological component of homeopathy can both be subjects of an implausibility argument.Howick suggests that the mechanistic reasoning used to reject Leibovici’s hypothesis is likely to be high-quality. I claim that the parallels between Leibovici’s hypothesis and the implausibility of homeopathy warrant considering whether the implausibility argument against homeopathy might also count as high-quality reasoning. This is despite the fact, as outlined above, that the mechanistic reasoning involved does not proceed in the typical way from presence of mechanism to presence of effect.not incomplete, i.e., there are no obvious gaps in our knowledge of the inferential chain linking the intervention and the patient relevant outcome.The knowledge of mechanisms upon which the mechanistic reasoning is based is The probabilistic and complex nature of mechanisms are explicitly taken into account when inferring from mechanisms to any claims that a particular intervention has a patient-relevant benefit. Neither of these criteria fit the implausibility argument perfectly. In both cases, it is assumed that mechanistic reasoning is being used to link an intervention to an effect. However, these criteria can be adapted for the absence of a mechanism. The first criterion, ‘not incompleteness’ bears on the implausibility argument, I suggest, by requiring evidence for premise (1) to be genuine evidence of absence and not absence of evidence. The claim that it is very implausible that there could be a mechanism should not rely on lack of knowledge about possible mechanisms, but rather, should rely on ‘not incomplete’ knowledge of why such a mechanism is very implausible. Leibovici’s study provides a good example of this: it is very implausible that remote retroactive prayer could be effective because any mechanism would have to contradict, or be a special exception to, the general and fundamental idea that causes precede their effects. That one cannot now cause events in the past is an example of the kind of ‘not incomplete’ knowledge that is required by Howick’s criterion.Howick argues that mechanistic reasoning ought to fulfil two criteria if it is to be counted as good evidence for a treatment effect. The second criterion, that complexity should be accounted for, is less straightforward to adapt. The spirit of this criterion comes from the observation by Howick that mechanisms are rarely, if ever, simple systems and many difficult-to-predict factors potentially affect whether a mechanism goes through. Consequently, I suggest that the evidence on which we claim that there cannot be a mechanism must be sensitive to the complexity that might exist between treatment and effect. To illustrate how this might affect plausibility arguments, consider that one might defend Leibovici’s result against apparent implausibility by noting that the supernatural properties of prayer exempt it from considerations based on cause and effect in the natural world. Proponents of homeopathy often make a similar kind of manoeuvre by invoking the complex physical–chemical properties of water. They often respond to implausibility claims with counter-arguments based on the macro-structures, fractals, or quantum properties of water , 52, 53.Given what both the STC report and the wider critical literature state about the implausibility of a mechanism by which the quasi-pharmacological component of homeopathy could be effective, does this qualify as high-quality evidence? I claim it does. To repeat, the STC claim that a mechanism would be ‘far removed from current scientific understanding’, and that homeopathic principles are ‘theoretically weak’ and present ‘enormous difficulties’. The claim in both the wider literature and the STC report is that there is good evidence that there cannot be a mechanism, not that there is no evidence for what the mechanism could be. If those claims are true (as the STC claim they are), then this must count as high-quality mechanistic reasoning. The claims that a mechanism for the effectiveness of the quasi-pharmacological component would contradict fundamental principles of physics, chemistry, and biology constitutes the kind of ‘not incomplete’ knowledge that fulfils Howick’s first criterion. The knowledge we have that (critics claim) allows one to rule out a mechanism for homeopathy is among our most fundamental background knowledge.Furthermore, fulfilling Howick’s second criterion, this knowledge is sufficiently general, so critics claim, that we can confidently assert that it is very implausible that there could be a mechanism without worrying that there may be some unconsidered or unknown mechanisms by which the quasi-pharmacological component could, in fact, be effective. Critics claim there is nothing complex about homeopathy that makes it a special exception. This is what motivates those very strong rhetorical claims that homeopathy ‘cannot’ work: the claim is that our evidential position is sufficiently strong to make the effectiveness of homeopathy a closed question.if one adopts the evidential position towards the implausibility of homeopathy that the STC adopt in their report, and which is also adopted in the wider critical literature. This is a conditional claim. I am not arguing that mechanistic reasoning about homeopathy should be taken as strong evidence. I am instead arguing that if one believes what the STC endorse in their report, then one should take mechanistic reasoning about homeopathy as strong evidence. Consequently, I claim that the STC have made a mistake by not doing this.It is important to note that I am not endorsing this as the correct evidential position to take. I claim that the implausibility argument constitutes high quality mechanistic reasoning The STC endorse the same evidential position as the wider critical literature about homeopathy. Both claim that it is very implausible that there could be a mechanism by which the quasi-pharmacological component of homeopathic treatment is effective. Unlike the wider critical literature, the STC do not build this into an ‘implausibility argument’ against homeopathy. They reject using plausibility considerations. I have argued that they do not give good reasons for their rejection of plausibility considerations.Furthermore, I have argued that the rejection of plausibility considerations does not follow from Howick’s refinement of the role that mechanisms should play in EBM. The STC report adopts the typical EBM view that mechanistic reasoning counts for very little. If homeopathic treatments were like other conventional drug treatments, then this would be the acceptable position to hold. The case of homeopathy is different however because of what the STC report claims about its implausibility. I have argued that the report’s statements about implausibility fulfil Howick’s criteria for being high-quality mechanistic reasoning (assuming that what the STC claim is true). As a result, evidence of implausibility should count in evaluations of whether the quasi-pharmacological component is effective, contrary to the approach taken in the STC report. On the basis of their own assessment of the evidence, the STC should have been able to make the implausibility argument. In doing so, they could have strengthened their case against homeopathy.There are two important points to note about this conclusion. Firstly, as I have emphasised, this conclusion is conditional. The STC can make a stronger argument only if their evidential claims are warranted. In fact, proponents of homeopathy may be in the better epistemic position here, since they only need to prevent the efficacy of the quasi-pharmacological component of homeopathy being ruled out to put the mechanistic debate ‘on the table’. That is to say, unless the strong evidential premise in the implausibility argument can be justified, it is not a sound argument. I have not discussed the to and fro between opponents and proponents of homeopathy, however, a key aspect of the controversy is the use of statements about plausibility to frame certain questions as open or closed, and to shift the burden of evidence in precisely this way. Again, coming back to the interaction between philosophical and sociological issues, an interesting epistemological question is whether a dialectical standard of evidence is appropriate in the debate over the assessment of homeopathy .Secondly, this conclusion is fundamentally about the consistency of the position adopted in the STC report. By adhering to a dismissive view of mechanistic reasoning , the STC report has failed to make the most of its own strong evidential claims. Consequently, the STC report’s position on the implausible effectiveness of homeopathic treatments provides a further example of the more general point that mechanistic reasoning should not be seen as providing categorically lower quality evidence. The implication of this is that any evaluation of the evidence for the efficacy of the quasi-pharmacological component of homeopathic treatment ought to take into account the mechanistic evidence for and against its purported efficacy. For homeopathy, and unlike most conventional treatments, the purported mechanisms and principles behind the treatment are directly relevant to the debate, if, as critics claim, they can be ruled out as highly implausible.


Adopting the interpretative/hermeneutical method typical of much legal scholarship, this article considers two sets of issues pertaining to LTDNA profiles as evidence in criminal proceedings. The section titled Expert Evidence as Forensic Epistemic Warrant addresses some rather large questions about the epistemic status and probative value of expert testimony in general. It sketches a theoretical model of expert evidence, highlighting five essential criteria: (1) expert competence; (2) disciplinary domain; (3) methodological validity; (4) materiality; and (5) legal admissibility. This generic model of expert authority, highlighting law's fundamentally normative character, applies to all modern forms of criminal adjudication, across Europe and farther afield. The section titled LTDNA Evidence in UK Criminal Trials then examines English and Northern Irish courts' attempts to get to grips with LTDNA evidence in recent cases. Better appreciating the ways in which UK courts have addressed the challenges of LTDNA evidence may offer some insights into parallel developments in other legal systems. Appellate court rulings follow a predictable judicial logic, which might usefully be studied and reflected upon by any forensic scientist or statistician seeking to operate effectively in criminal proceedings. Whilst each legal jurisdiction has its own unique blend of jurisprudence, institutions, cultures and historical traditions, there is considerable scope for comparative analysis and cross-jurisdictional borrowing and instruction. In the spirit of promoting more nuanced and sophisticated international interdisciplinary dialogue, this article examines UK judicial approaches to LTDNA evidence and begins to elucidate their underlying institutional logic. Legal argument and broader policy debates are not confined to considerations of scientific validity, contamination risks and evidential integrity, or associated judgments of legal admissibility or exclusion. They also crucially concern the manner in which LTDNA profiling results are presented and explained to factfinders in criminal trials. As originally conceived, this Research Topic focused on “the interface between forensic scientists and statisticians when calculating likelihood ratios for low template and complex DNA results”This article considers two sets of issues pertaining to LTDNA profiles as evidence in criminal proceedings, which are pertinent to all modern legal systems in which this type of evidence is currently or might in future be adduced. The section titled Expert Evidence as Forensic Epistemic Warrant addresses some rather large questions about the epistemic status and probative value of expert testimony in general. The following section on LTDNA Evidence in UK Criminal Trials then examines English courts' attempts to get to grips with LTDNA evidence in recent cases. These efforts might or might not appear impressive to outsiders, but they do, generally speaking, follow a predictable judicial logic—a logic which might usefully be studied and reflected upon by any forensic scientist or statistician seeking to operate effectively in this system of justice. In the spirit of promoting more nuanced and sophisticated interdisciplinary dialogue this article examines judicial approaches to LTDNA evidence and begins to elucidate their underlying institutional logic.The following discussion adopts the interpretative or hermeneutical method typical of much legal scholarship. It engages with primary and secondary institutional materials—prominently featuring reported criminal appeals in England and Wales—in an attempt both to understand judicial practice and to contribute to the best normative (re)interpretation of legal doctrine and institutions. It might fairly be conceptualized, in methodological terms, as an elucidation of the internal logics of legal argumentation and judicial reasoning, which are often opaque to non-lawyers, even to those such as forensic scientists who regularly participate in criminal investigations and are no strangers to courtrooms. In striking contrast to scientific knowledge, law is delimited by jurisdiction. The second half of this article discusses appellate decisions drawn from two specific, common law jurisdictions: Northern Ireland (applying Northern Ireland law), and England and Wales (applying English law). Whilst each legal jurisdiction has its own unique blend of jurisprudence, institutions, cultures, and historical traditions, there is considerable scope for comparative analysis and cross-jurisdictional borrowing and instruction, the more so in a shrinking world characterized by globalization and cosmopolitan legality. Better appreciating the ways in which UK courts have addressed the challenges of LTDNA evidence may offer some insights into parallel developments in other legal systems. Moreover, the practical challenges posed by forensic science and other expert witness testimony cut across conventional Comparative Law distinctions between “adversarial” and “inquisitorial” procedures or “common law” and “civilian” legal systems. In setting the scene for more detailed doctrinal analysis, the first part of this article presents a generic model of expert authority highlighting law's fundamentally normative mission which applies to all modern forms of criminal adjudication, across Europe and farther afield.not see the incident to testimony from witnesses who did. “Best” does not mean infallible. Evidence adduced in criminal trials is often contested or contradictory, and the factfinder must make the best of it, resolving any enduring doubts in accordance with the applicable burden and standard of proof. In criminal litigation, most  doubts are resolved in favor of the accused, in accordance with the presumption of innocenceCriminal trials are practical exercises in reasoning under uncertainty. We want to know what happened; but material facts are contested (otherwise the accused would have pleaded guilty in common law systems). Relevant evidence rationally authorizes or “warrants” particular inferential conclusions. The more probative value evidence has, the more warrant it provides for the conclusion. In traditional common law thinking, the best evidence is the oral testimony of a percipient witness, given on oath, and tested through cross-examination. This category of evidence is regarded as providing the best epistemic warrant for the inferential conclusions supported by the witness's testimony. This doesn't mean to say, of course, that every witness in court is truthful, accurate and reliable. We know, for example, that there can be many kinds of difficulty with eyewitness testimonytrust me, I'm an expert. The authority paradigm underpinning the inferential logic of forensic expert testimony has five major components: (1) the expert is a genuine expert (competence); (2) in a field in which expertise can be obtained (domain); (3) and has correctly and conscientiously applied authentic domain-specific protocols to produce proffered evidence ; (4) in relation to a legally relevant issue ; (5) and in a form that is likely to provide legitimate epistemic warrant for legal adjudication (admissibility). The authority paradigm is generic. It applies to “sciences” as conventionally understood , but also to historical, social and psychological facts, and even to moral and theological reasoning. This 5-fold taxonomy, albeit a necessarily simplifying model, offers a powerful heuristic for teasing out theoretical complexities and practical challenges entailed by the familiar-sounding notion of forensic expertisead hominem) than any criticism that individual exponents have not taken the appropriate training courses or gained enough job-related experience.Expert evidence supplies inferential warrant through the argument from authority. The expert says to the court, expert opinion. Judges may be ill-equipped and trial procedure ill-suited to policing experts' disciplinary boundaries effectively.Methodological validity, component (3), embraces a set of important epistemic considerations arising even in relation to genuine experts in well-established disciplinary domains. The authority paradigm breaks down for different reasons when genuine experts succumb to personal or professional biases, fail to implement pertinent methodological protocols correctly, or purport to speak beyond the boundaries of their domain-specific expertise. It may be difficult in the general run of cases for courts to differentiate between genuinely well-credentialed experts, and plausible-sounding charlatans and shystersnormative. The overriding objective of criminal proceedings is doing justice;in the right way (“by due process of law”), not any which way—e.g., by vigilante lynch mob or Dirty Harry policingComponents (4) and (5) of the authority paradigm—materiality and admissibility—introduce further major complexities, in terms of managing the interface between expert knowledge and forensic objectives, concerns and values. A vital distinction is that, whereas components (1)–(3) are essentially epistemic matters, criminal adjudication is fundamentally epistemic not ontological: it relates to the status of our knowledge and beliefs about facts in the world, not to the facts themselves (setting aside complications arising from quantum physics and sub-atomic particles not pertinent to the present discussion). Judgments of justice are of an entirely different, normative, order. It is not merely doubtful or uncertain whether, say, it would be just or fair if Drug X cured cancer; or just or fair if the accused were the donor of crime scene DNA. Such questions are incoherent. They perpetrate a category error, confusing normative standards with empirical facts.It is at this point in the discussion that, in my experience, lawyers and scientists tend to see things differently; and misunderstandings easily arise. Science investigates empirical matters, and produces factual information about the world. It is epistemic to its core and overwhelmingly instrumental in outlook. The policy paradigm is “curing cancer.” A new drug either works (in part), or it does not. It has particular side-effects (in some degree), or it does not. It can be manufactured by a particular process, or it cannot. Likewise, the DNA collected from the crime scene was either deposited by the accused, or by somebody else; the accused lacked capacity to form the required intention at the material time , or he did not; and so on. These are all facts about the  world; they are either true or false; and they invoke or presuppose causal explanations. This is not to say or imply that “science” always provides unequivocal, certain answers to discrete, well-formulated questions. To the contrary, scientific investigation is inherently uncertain , and conclusions are typically framed in probabilistic terms—whether or not employing explicitly quantitative measurements of uncertainty in numbers or words. But the equivocation introduced by resorting to probability is adequate warrant for the purposes of determining criminal liability and censuring and punishing criminal wrongdoers. By reframing the issue in this way, it should become clearer why expert evidence cannot provide its own epistemic warrant for judicial purposes, no matter how highly the evidence scores on components (1)–(3) of the authority paradigm. Expert witnesses do not decide what evidence is “good enough” for the purposes of criminal adjudication. This is the role of the legally, indeed constitutionally, authorized fact-finder. Furthermore, issues of materiality and strategic application in individual cases are determined by legal standards and judicial decision-makers, not by the disciplinary standards embraced by particular sciences or expert witnesses. This insight goes to the heart of the truism that forensic science serves justice, not the other way around.Criminal adjudication comprises a set of institutionalized practices for determining liability and censuring and punishing criminal wrongdoingirrespective of the epistemic credentials of expert evidence, encapsulated in authority paradigm components (1)–(3). Normative pluralism and jurisdictional diversity are inherent features of modern legality requiring detailed local knowledge and careful negotiation, not least on the part of expert witnesses operating in multiple jurisdictions. However, these elements of cultural relativity tend to provoke intuitive resistance form scientists accustomed to prioritizing universal  scientific truth over national ideology. In one sense, skepticism is justified: sacrificing science to ideology in general, and regardless of political variety, leads to Lysenkoism, authoritarianism, crop failure and mass starvation. Nonetheless, the subservience of science to normative criteria is an inherent, fully rationalized and legitimate requirement of penal justice.The logic of the authority paradigm and the priority of normative over epistemic considerations in criminal adjudication are general features of all modern legal systems. However, the ways in which resulting interfaces are organized, opportunities exploited, and tensions managed vary considerably from one legal system to the next, working with the grain of local procedural traditions, institutional practices and professional cultures. For example, in the common law world lay fact-finding is still regarded as significant , whilst lay input in criminal adjudication is diminished or even non-existent in most Continental juristic traditions. The roles, relationships, and distribution of powers between judges, prosecutors and defence lawyers also vary considerably across legal jurisdictions. In legal systems with stronger adversarial leanings, prosecutors and defence lawyers tend to play a more active role in shaping the course of the proceedings, whereas the “inquisitorial” judge is the dominant figure in other procedural models. Criminal procedure is dynamic and constantly evolving , and it is always perilous to over-generalize abstract formal models or to extrapolate too confidently from national traditions. It follows that approaches to expert evidence in general, or to particular types of scientific evidence such as LTDNA, which are utilized successfully in one jurisdiction cannot automatically be expected to operate with the same success, or at all, in a different procedural environment structured by alternative normative priorities. This observation holds Two kinds of recurrent problems with expert evidence call for practical solutions in all legal systems. The first is the problem of expert disagreement; the second, more fundamental problem concerns a recurrent dynamic between deference and education in reliance on expertise. What should a court do when expert witnesses disagree? An attractive first option would be to find that, on further investigation, there is no genuine disagreement to resolve, e.g., because one of the protagonists is not really an expert after all, or not an expert in the relevant domain, or because the experts have been fed different factual assumptions by their instructing lawyers, and once these discrepancies have been clarified the ostensible disagreement disappears. But this convenient resolution will not always be possible. In cases of genuine, well-informed, unshakeable disagreement between experts, various strategies are available to the court. One approach would be to accept the disagreement as a forensically significant fact in and of itself and resolve the issue in accordance with the burden and standard of proof Legal systems resolve these pervasive issues of expertise in their own distinctive ways. At the level of sweeping generalization, common lawyers tend to think that “civilians don't try”Recent attempts by criminal courts in England and Wales and Northern Ireland to get to grips with LTDNA profiling evidence must be interpreted in light of the conceptual, normative and juridical considerations summarized in the previous section. The five principal components of the authority paradigm and the diversity of national criminal procedures within a shared ECHR framework mandating fair trials, in particular, need to be borne in mind as the exposition unfolds. Just as the entirety of western philosophy has evolved in productive antagonism with skeptical doubt, legal recognition of LTDNA profiling was propelled by challenges to its methodology, epistemic status and evidential reliability. The evolution of English criminal jurisprudence on LTDNA profiling may find some resonances with parallel developments in other legal jurisdictions, and possibly inform legal argument and policy debates in criminal trials and appeals elsewhere.R v HoeyOur story begins in 2007 with the judgment of the Northern Ireland Crown Court in [O]ne police and SOCO witness after another and also Dr. Griffin [of FSNI] had candidly made clear that possible examination for DNA was not in their minds at all as they were collecting, storing, transmitting and dealing with these items in 1998. Why therefore would they then have had present to their minds and been complying with the exacting integrity requirements which reliable DNA examination and most especially that in its LCN form demands? All this [FSNI] must have known very well when it co-operated in searching for and collecting items for LCN examination in Birmingham and again later when the idea of using the results of those examinations as evidence in this trial must have been under discussion. By that stage the problems inherent in the need to prove integrity had plainly come to be appreciated by one or more police officers concerned in this investigation as was shown by the mendacious attempts to retrospectively alter…evidence so as to falsely make it appear that appropriate DNA protective precautions had been taken at that scene.…[H]aving carefully reviewed all the evidence on this issue, I am not in the least satisfied in relation to any one of the items upon which reliance is sought to be placed for the results of their LCN DNA examinations that the integrity of any of those items prior to its examination for that purpose has been established by the evidence. Accordingly I find that that DNA evidence…cannot satisfy me either beyond a reasonable doubt or to any other acceptable standardThat is to say, in terms of the conceptual framework sketched in the previous section, the DNA profiling evidence lacked adequate epistemic warrant for grounding a criminal conviction, owing to the well-established fact that forensic samples were compromised—at least in the sense that their integrity could not be demonstrably assured.Weir J's judgment might have stopped there, but instead briefly addressed the validity and merits of LCN profiling techniques themselves, since these had been extensively canvassed during the trial and conflicting expert views had been expressed. Weir J was “concerned at the wide variance in expert opinions, not only as between the Prosecution and Defence but also between the two experts called for the Prosecution,”R v Hoey did not create a binding legal precedent (not even in Northern Ireland), and Weir J's remarks on LCN DNA profiling were strictly obiter dicta, i.e., not part of the formal legal holding in the case. It was nonetheless a widely reported judgment in a very high profile trial, which sparked much agitated discussion amongst forensic scientists and led the Association of Chief Police Officers (ACPO), in consultation with the Crown Prosecution Service (CPS), to recommend temporary suspension of LCN profiling techniques in criminal investigations and prosecutions pending further inquiry and review. The science of LTDNA analysis, defined as “[a]n ultra-sensitive technique that has the potential to yield a DNA profile from sub-optimal biological samples e.g., Low Copy Number DNA analysis,”Hoey regarding the absence of reliable validation were characterized as “well-founded.”Being a decision at first instance, Interpretation of the results is complex for two reasons: the statistics are challenging and probably hard to comprehend by a non-specialist and the decision how and when to apply certain statistical methods has not yet reached a clear consensus…the challenges in terms of statistical interpretation of the data and in communicating them to a largely innumerate criminal justice system should not be under-estimated, nor should the importance of earning and maintaining public confidence in the systemThese observations appropriately acknowledge the broader institutional context and social expectations of evidential (epistemic) warrant for criminal verdicts. The Caddy Review recommended that “any LTDNA profile should always be reported to the jury with the caveats: that the nature of the original starting material is unknown; that the time at which the DNA was transferred cannot be inferred; and that the opportunity for secondary transfer is increased in comparison to standard DNA profiling.”A follow-up report issued by the Forensic Science Regulator concurred that “the science underpinning the LTDNA analytical services, as provided to the CJS [criminal justice system], is sound and that…suppliers offering such services have properly validated their processes. There is no flaw inherent in the process which prevents its use within the CJS.”As long as the scientist reporting the results of LTDNA analysis complies with the duties and obligations placed on expert witnesses the CJS will appreciate the nature and value of the evidence providedR v ReedThis was the state of play, in technical and policy circles, when the Court of Appeal in England and Wales came to consider the status of LTDNA evidence in criminal trials in a clutch of criminal appeals in 2009 and 2010, beginning with Reed and Reed actually comprised two conjoined appeals arising from separate trials, both of which involved challenges to LCN DNA profiling evidence. In Reed itself, genetic material was recovered from pieces of plastic which the prosecution contended had broken off from a knife handle employed as the murder weapon. In Garmson, the accused was identified as the rapist from small amounts of DNA deposited on the victim's lips, undergarments and tampon. Primed by Weir J's widely reported reservations in Hoey and the Caddy Review's findings, the Court of Appeal—led by Thomas LJ, who has since been promoted to Lord Chief Justice—embarked upon a thorough reconsideration of LCN and LTDNA profiling evidence, and directed the parties to assist the Court, within the framework of judicially managed pre-trial case preparation implemented by the Criminal Procedure Rules (CrimPR) since 2005 (and regularly updated). These exchanges produced the following fixed points of agreement: (1) the “standard kit” employed in DNA profiling using the SGM+ system was “designed optimally to produce a full profile on 1 ng which is the approximate equivalent of 160 human somatic cells which typically can be visualized in a tiny blood spot”The case popularly known as Reed announced the following principles of admissibility:Drawing on the technical data and expert opinions canvassed before it and adduced in evidence, the Court of Appeal noted the importance of “the stochastic threshold” at which “the profile is unlikely to suffer from stochastic effects  which prevent proper interpretation of the alleles.”[A] challenge to the validity of the method of analysing Low Template DNA by the LCN process should no longer be permitted at trials where the quantity of DNA analysed is above the stochastic threshold of 100–200 picograms.…There may be cases where reliance is placed on a profile obtained where the quantity of DNA analysed is within the range of 100–200 picograms where there is disagreement on the stochastic threshold on the present state of the science. We would anticipate that such cases would be rare and that, in any event, the scientific disagreement will be resolved as the science of DNA profiling develops. If such a case arises, expert evidence must be given as to whether in the particular case, a reliable interpretation can be made. We would anticipate that such evidence would be given by persons who are expert in the science of DNA and supported by the latest research on the subject. We would not anticipate there being any attack on the good faith of those who sought to adduce such evidenceobiter, because the DNA evidence in both appeals in Reed was above the threshold, and the appeals were ultimately argued and determined on issues of transference and persistence of DNA traces, not on the validity of profiling techniques. However, this  legal objection would predictably fail to gain judicial traction in subsequent cases, given the institutional status and authority of the Reed judgment. It would be perfectly evident to experienced lawyers that a senior court was deliberately articulating guidance to be followed in future criminal trials and appeals, with the firm expectation of compliance.Here we see the Court of Appeal  laying down the law in relation to the admissibility of LTDNA profiling evidence. There is no general statutory test governing the admissibility of expert evidence in England and Wales. Admissibility is governed by common law principles,Reed are interesting at a number of levels. They are animated by the strong desirability of providing clear and reasonably determinate guidance to prosecutors, defence lawyers and trial judges in the conduct of criminal litigation. It would hardly be efficient to try to re-litigate the existence and calibration of stochastic thresholds in each and every criminal trial involving LTDNA profiling evidence, and it would—to say the least—be highly undesirable for individual courts to be improvising their own, quite possibly discrepant, thresholds, depending partly on which expert witnesses happened to testify in particular trials and how their evidence was received and assessed by individual trial judges in admissibility determinations  that evidence pertaining to stochastic thresholds “would be given by persons who are expert in the science of DNA and supported by the latest research on the subject” might sound like no more than a reiteration of common sense legal orthodoxy, extrapolating from the competency and domain components of the standard authority paradigm for expertise outlined in the previous section. In fact, these loaded remarks were intended to signal the Court's impatience with defence testimony challenging the validity and inferential logic of DNA profiling evidence, based not on direct practical experience in profiling, but on generic principles of scientific validation, methodology and inferential logic. Of one defence expert witness, the Court of Appeal remarked:R v Hoey, let alone to assist in the attack made in that case on the LCN process, he has given evidence in so many Low Template DNA cases since then on the strength of the observations in R v Hoey that he has acquired a degree of experience from these cases, his discussion with others and his reading of papers. We retain clear reservations about the extent of his expertise in relation to DNA profiles…He gives evidence with a degree of gravitas and fluency that is impressive and is able to explain concepts clearly. However, his expertise on the interpretation of DNA profiles is limited, without any relevant first hand laboratory or research experience. He is not qualified to make a scene of crime investigation…Whilst it is impossible to understand how he had sufficient expertise to be able to give evidence in Reed may have allowed itself to be gulled by another .In relation to a second defence expert, the Court complained that “his experience is of a different jurisdiction where the scientist who gives evidence may have a narrower type of expertise and the scope of evidence an expert can give may not be the same as the scope in this jurisdiction.…[H]is experience was not based on the work of a forensic scientist in this jurisdiction who attends both the scene of the crime and supervises the laboratory work.”R v BroughtonLord Justice Thomas' prediction, or pious hope, that cases involving LTDNA profiles arguably under the stochastic threshold “would be rare” was soon put to the test. In Reed had already decided that profiles below the stochastic threshold range of 100–200 picograms are inadmissible in English law. The Court of Appeal in Broughton made short work of the faulty logic in this submission:One argument advanced on appeal was that Reed & Reed. This court recognised that in the current state of technology there is a stochastic threshold between 100 and 200 picograms above which LTDNA techniques…can be used to obtain profiles capable of reliable interpretation. Specifically, the court observed that above this threshold a challenge to the validity of the method of analysing LTDNA by the LCN process should not be permitted in the absence of new scientific evidence. However, the court did not hold or make any observation to the effect that below the stochastic threshold DNA evidence is not admissibleThe appellant's submission is…founded upon a misunderstanding of the decision in The defence argument that LTDNA profiles below the stochastic threshold are automatically inadmissible resurfaced in a second appeal heard later in the year, involving DNA mixtures from more than one donor, and it was once more emphatically rejected. The Court of Appeal reiterated that “what mattered was the quality of the minor profiles and not the quantity.…[P]rofiles obtained from < 200 picograms can be reliable. It is reliability that is the issue, not the quantity, though plainly the quantity is relevant…to the consideration of stochastic effects.”Broughton “were derived from unquantified samples of DNA of < 100 picograms and that this raised entirely legitimate grounds for scientific dispute which the appellant was right in testing before the judge.”A more promising line of attack was to challenge the profiling evidence on its own scientific merits. The Court of Appeal recognized that the profiles adduced in [T]here is now a considerable body of opinion from respected independent scientists and the Forensic Science Regulator that LTDNA techniques, including those used to generate the profiles relied upon by the Crown in this case, are well understood, have been properly validated and are accepted to be capable of generating reliable and valuable evidence. At these very low levels of DNA, the dangers presented by the possibility of stochastic effects, including allelic drop-out, drop-in and stutter are very real and must be fully appreciated, but they may often be addressed by repeating the process a number of times…potential shortcomings of LTDNA profiles, however, the Court of Appeal was satisfied that the pertinent issues had been fully ventilated in the trial and that the evidence actually generated and adduced in the instant case had been properly explained and vindicated by competent experts:Observe, again, the instrumental role of the Forensic Science Regulator in authenticating the underpinning science and validation processes. If—and for as long as—the Regulator is satisfied on these technical questions, the courts are likely to follow her[A]ll of the consensus alleles match those in the appellant's profile. In other words, the consensus profiles do not suggest the procedures suffered from drop-in or stutter such as to render the results inherently unreliable. Indeed, this is reflected in the statistics [sic] derived from the consensus profiles to which we have referred and about which there was no dispute. At their most powerful and when derived from all duplicated components, these give rise to the match probability of < 1 in 1 billion. We believe that these were all matters properly admitted in evidenceBroughton had satisfied itself that the trial judge had adopted the correct approach to assessing the admissibility of LTDNA evidence, that question was settled for the purposes of this appeal. But the Court still had something it wanted to get off its chest, and the Judgment had a sting in the tail.It is important to appreciate that criminal appeals in England and Wales are not re-trials, as they are in many continental European jurisdictions. The Court of Appeal in England and Wales performs an essentially reviewing function, and is primarily concerned with the legality and fairness of trial proceedings, not with the accuracy of their outcomes. Crucially, the Court of Appeal does not second-guess jury verdicts. Once the Court in The Court signaled a general concern about defence tactics in challenging the credibility and “integrity” of experts presenting DNA profiling evidence:Whatever may be the position in other jurisdictions, it is the duty of an advocate and an expert in this jurisdiction not to embark upon an attack on the integrity of other experts unless there is an evidential basis for doing so. There was none in this case. The attack made on the integrity of LGC Forensics and Cellmark was without foundation and should never have been made…[T]here can well be a difference of opinion between experts on LTDNA, but there should be no question of the good faith of those involved in LTDNA being put in issue. This is a case where there is a proper disagreement between experts but the course taken by those giving evidence on behalf of the appellant went into matters for which there was no foundation. Not only was the attack on the good faith of the Crown's witness wholly deplorable and unwarranted, but it also was a great disservice to the appellant's caseBroughton, specifically, “an attack was made…on the integrity of LGC Forensics; it was alleged that their commercial interests and influence over their case workers had tainted their professionalism and objectivity. LGC Forensics were underestimating the problems which were associated with LTDNA and promoting its viability for financial reasons.”judicial impartiality, the court must be manifestly, not merely actually, unbiasedseen to be done. How much of this expectation carries over to expert witnesses utilizing techniques from which their employers derive a commercial advantage is a nicely balanced question.The Court is here saying that not only are such credibility attacks contrary to ethical standards of advocacy, and therefore liable to get counsel into hot water with their professional regulatorBroughton unraveled on appeal.Once evidence has been ruled admissible, attention shifts to its uses and probative value in the trial. An important dimension of evidentiary regulation, and one which has been assuming greater prominence in many common law jurisdictions including England and Wales over the last several decades, concerns judicial directions to the juryBroughton was faced with the task of directing the jury in relation to a disagreement between the expert witnesses regarding the possibility that the DNA sample in question may have been a mixed profile. The expert witness called by the prosecution testified that she was satisfied, on the basis of her experience, that rogue profiling results obtained during the analytical process could be set aside as artefactual stochastic effects. Expert evidence adduced by the defence challenged this conclusion. It was argued that profiling results were consistent with the presence of an unidentified donor, and since the possibility of a mixed sample could not be ruled out, the match probabilities quoted by the prosecution's expert were invalid. The trial judge in his summing-up reminded the jury of this disagreement, which had been characterized as a legitimate difference of opinion between genuine experts. “In other words,” he explained, “there is no, as it were, answer at the back of the book. There is no independent machine if people hold contrary views to tell you in these circumstances who is right and who is wrong. It is a question of expert evidence and scientific judgment…”The trial judge in Readers of this scientific journal might well be thinking that this direction was incoherent, as a DNA “match” may be close to meaningless, or at least dangerously misleading, in the absence of a valid RMP. The Court of Appeal thought so, too, and concluded “with considerable regret”[T]he judge…fell into error in directing the jury that, in those circumstances, they could reach their own conclusions on the DNA evidence. It is fair to say that the judge urged the jury to exercise caution and be very careful in arriving at firm conclusions because they were not experts in statistics. However, we believe that only served to emphasise the void in which they were left. They had no guidance from the experts and no guidance from the court to enable them to conduct an evaluation of the evidence for themselves.…[T]he judge ought to have directed the jury that if [the prosecution's expert] was wrong in her conclusion that the DNA profiles were single rather than mixed, then on the only evidence before the court at the trial the DNA evidence must be disregarded. The judge having failed to do so, the jury may well have embarked upon a task of evaluation for which they were not equipped. This means their verdict cannot be regarded as safeBroughton underlines the point that admissibility is not the only important evidentiary issue raised by LTDNA profiles. The way in which profiling evidence is communicated to lay factfinders is also of fundamental importance if jury verdicts are to secure adequate epistemic warrant and broader normative legitimacy. In all other respects, the trial judge's “admirable summing up” in Broughton had “expertly addressed all the evidence and the complex issues in clear terms about which no complaint…could possibly be made.”both the underlying science of profiling and the statistical foundations and probabilistic logic of valid RMPs, trial judges may inadvertently put a foot wrong, with potentially tragic consequences.This case history might be interpreted, especially by readers more accustomed to inquisitorial procedures , as a cautionary tale about the hazards of disaggregated tribunals in criminal adjudication and the perils of fastidiously microscopic appellate scrutiny of the wording of judicial directions to juries. These charges are not without substance; but the common lawyer has this riposte. In the absence of any parallel procedure in continental criminal trial proceedings, wherein lies the assurance that judges have any better understanding of the logical foundations of LTDNA evidence and can competently assess its probative value? Do reasoned judgments typically contain sufficiently detailed “motivations” to enable such assessments to be made, by an impartial observer or by the public at large? One could only begin to answer such questions through sustained research and on a jurisdiction-by-jurisdiction basis, but my own fragmentary and partly anecdotal acquaintance with judicial practice in continental Europe suggests that these are pertinent questions to add to our shared research agenda.R v Hoey,ad hoc development of common law tests, approaching LTDNA profiling evidence in much the same way as DNA evidence itself was first addressed 30 years agoReedBroughton, to produce the following doctrinal conclusion :Forensic DNA profiling demands cooperative interdisciplinary expertise in forensic science, statistics and law. This article has reviewed UK courts' responses to LTDNA profiling, starting with initial skepticism in [T]he science of LTDNA is sufficiently well-established to pass the ordinary tests of reliability and relevance and it would be wrong wholly to deprive the justice system of the benefits to be gained from the new techniques and advances which it embodies, in cases where there is clear evidence…that the profiles are sufficiently reliablequality of the profiling evidence in the instant case, as vouchsafed by experienced experts. There is no arbitrary stochastic threshold above which LTDNA evidence is admissible, and below which it is automatically excluded.Reliability, moreover, is primarily a function of the rationes decidendi . Judgments rendered by common law courts are complex pieces of legal literature that must be interpreted against a backdrop of “thick” institutional practice and cultural meaning. Some of the factors in play, including the structural logic of the argument from authority sketched in the first part of this article and the priority of normative over epistemic considerations in criminal adjudication, are universal features of modern legal systems. Other factors reflect more local dynamics pertaining to the structural logic of criminal procedure, national legal traditions, and broader features of culture and society . The second half of the article surveyed the principal arguments and judicial rationales that have been deployed in English criminal appeals concerned with LTDNA profiling evidence, pointing out their broader institutional context and resonances and explaining why some gained traction whilst others were rejected. The issues, we saw, are not confined to considerations of scientific validity, contamination risks and evidential integrity, and associated judgments of legal admissibility or exclusion. They also crucially concern the manner in which LTDNA profiling results are presented and explained to lay factfinders in criminal trials.There is, however, much more to be gleaned from English jurisprudence on LTDNA profiling evidence than these “headline” qua epistemic warrant) of criminal adjudication.If opinions differ concerning the adequacy of English courts' responses to LTDNA evidence, this may in part reflect divergent understandings of the deeper structural logic and values of criminal adjudication. These deeper structures are always engaged, and ought to be elucidated and consciously considered, whenever the admissibility and uses of expert evidence are placed under the policy microscope or raise novel legal issues for courts. Because policy questions are fundamentally normative  rather than factually empirical or “scientific,” legal jurisdictions must, in the final analysis, decide what is best for themselves, within the broad parameters of international legal consensus on fundamental rights and democratic values and in harmony with local juristic traditions and cultures. But just as surely as the fact that technical standards of DNA profiling or statistical science cannot dictate the terms of criminal justice, modern legal systems committed to post-Enlightenment conceptions of fact-finding and proof must necessarily rely on the best available scientific and other technical advice, communicated via competent, domain-specific expert evidence, to underpin the rationality (The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Lasiopodomys brandtii) were maintained in a group (huddling) or as individuals (separated) and were exposed to warm (23 ± 1 °C) and cold (4 ± 1 °C) air temperatures (Ta).Huddling is highly evolved as a cooperative behavioral strategy for social mammals to maximize their fitness in harsh environments. Huddling behavior can change psychological and physiological responses. The coevolution of mammals with their microbial communities confers fitness benefits to both partners. The gut microbiome is a key regulator of host immune and metabolic functions. We hypothesized that huddling behavior altered energetics and thermoregulation by shaping caecal microbiota in small herbivores. Brandt’s voles  and nonshivering thermogenesis (NST) than voles exposed to warm Ta. Huddling voles had lower RMR and NST than separated voles in cold. In addition, huddling voles had a higher surface body temperature (Tsurface), but lower core body temperature (Tcore) than separated voles, suggesting a lower set-point of Tcore in huddling voles. Both cold and huddling induced a marked variation in caecal bacterial composition, which was associated with the lower Tcore. Huddling voles had a higher α and β-diversity, abundance of Lachnospiraceae and Veillonellaceae, but lower abundance of Cyanobacteria, Tenericutes, TM7, Comamonadaceae, and Sinobacteraceae than separated voles. Huddling or cold resulted in higher concentrations of short-chain fatty acids (SCFAs), particularly acetic acid and butyric acid when compared to their counterparts. Transplantation of caecal microbiota from cold-separated voles but not from cold-huddling voles induced significant increases in energy intake and RMR compared to that from warm-separated voles.Voles exposed to cold Tcore, mediates cold- and huddling-induced energy intake and thermoregulation and therefore orchestrates host metabolic and thermal homeostasis. It highlights the coevolutionary mechanism of host huddling and gut microbiota in thermoregulation and energy saving for winter survival in endotherms.These findings demonstrate that the remodeling of gut microbiota, which is associated with a reduction in host The online version of this article (10.1186/s40168-018-0473-9) contains supplementary material, which is available to authorized users. Octodon degus) and short-tailed field voles (Microtus agrestis) demonstrated that huddling reduced resting metabolic rate (RMR) and energy intake and that these metabolic advantages of huddling increased with lowered ambient temperature and increased group size [Social animals and humans have evolved cooperative behaviors to maximize their fitness in harsh environments –3. Amongoup size –10.The coevolution of mammals with their microbial communities confers fitness benefits to both partners –13. SmalLasiopodomys brandtii), a small non-hibernating herbivorous rodent species, are widely distributed in Inner Mongolian grasslands of China, Mongolia, and Southeast Baikal region of Russia. Its habitat is characterized by extremely cold dry winter and deep frozen soil. Brandt’s voles show seasonal variations in energy metabolism and thermoregulation to adapt to the seasonal environments [Brandt’s voles . After weaning (at 3 weeks of age), the voles were housed with the same sex siblings at a light regime of 16-h light:8-h dark (lights on from 4:00 to 20:00) and room temperature of 23 ± 1 °C. The voles were fed a standard rabbit pellet chow  and were provided with water ad libitum. The animal procedures were approved by the Animal Care and Use Committee of Institute of Zoology, CAS.A total of 124 female voles (aged 4 months) were placed in 31 cages (4 voles/cage) and were divided into 4 treatments: cold (at 4 ± 1 °C) huddling , cold separated , warm (at 23 ± 1 °C) huddling , and warm separated . Sibling voles were chosen preferentially and were acclimated to the cage (42 cm × 27 cm × 20 cm) for 3 weeks and then to the treatment conditions for another 3 weeks. The cages contained four equal compartments separated by stainless steel walls with small holes (6 mm in diameter). Openings (7 cm × 7 cm) in the walls allowed movement among the compartments. The openings were open for the huddling groups but closed for the separated groups, which had olfactory, visual, and vocal contacts. Individual voles were dyed on different positions of the body for identification.Voles were weighed at the beginning (day 0) and the end of (day 28) of the study using an electronic balance , and body weight change was calculated. Food was provided ad libitum and food intake and fecal output were measured for three consecutive days in the last week of acclimation . Uneaten2 uptake were taken for 2 h. An average of a minimum of three consecutive stable readings was taken as the RMR.RMR, measured as oxygen consumption, was determined in huddling and separated voles at their acclimated temperatures of 4 and 23 °C at the end of the experiment. An open-circuit respirometry system  with an air flow rate of 3 L/minute was used. Voles were maintained in a 5.8 L transparent metabolic chamber (type II for rats) with double-layered meshes for the separation of voles during the measurements. The animals were allowed 1 h for acclimation to the conditions, and then recordings of Ob-0.4  [NST was determined on individual animals at 25 °C on the day after RMR measurements. The volume of metabolic chamber was 2.7 L (type I for mice). The voles were injected subcutaneously with norepinephrine (NE)  at a dosage of 2.53Mdy mass) . NST wasTsurface) was read with an infrared camera  from a distance of 40 cm, and the data were analyzed by FLIR Tools software [Tsurface was averaged from seven to eight images for each cage. The perimeter temperature (Tp) of the voles was determined by fitting a polygon around the individual animal in the case of separated animals and around the entire group for huddling animals using the option “isotherm” of the software. The highest temperature in an image was selected as the maximum temperature (Tm). Furthermore, the contact temperature (Tc) between two animals in the huddling groups was determined by the “mobile” option.In the last week of acclimation, surface body temperature  was recorded during the acclimation period through transponders  implanted in the abdomen of one vole in each cage (n = 4–5 voles/group). The voles were anesthetized by intraperitoneal injection of pentobarbital sodium (50 mg/kg). After the abdominal skin was sterilized with iodophor, an incision of up to 1 cm in length was made below the diaphragm. The wound was closed with absorbable PGA surgical suture  and sterilized with iodophor again. The animals were allowed 10 days to recover from surgery [Core body temperature  with a GC autosampler and a FID system by the modified method [At the end of experiment, one vole from each cage (but not the one with E-Mitter) was sacrificed by COd method , 47. Caed method , 47. Sepn = 6 voles/group). Our target was the V3–V4 hyper-variable region of the bacterial 16S rRNA gene. PCR was started immediately after the DNA was extracted. The 16S rRNA V3–V4 amplicon was amplified using 2 × Taq PCR MasterMix . Two universal bacterial 16S rRNA gene amplicon PCR primers (PAGE purified) were used: forward primer-341F (CCTACGGGNGGCWGCAG) and reverse primer-805R (GACTACHVGGGTATCTAATCC) [w/v) agarose gels in TBE buffer  stained with ethidium bromide (EB) and visualized under UV light. PCR products were pooled and purified using Agencourt AMPure XP magnetic beads (Beckman) according to the manufacturer’s instructions. Then Sequencing was done on an Illumina HiSeq 2500.DNA from caecal contents was extracted by 2 × CTAB (cetyltrimethyl ammonium bromide), phenol chloroform mixture . In the later steps of DNA isolation, we used the spin column from SanPrep Column DNA Gel Extraction Kit  (based on a silica gel membrane) to purify and recover the DNA rapidly. DNA concentration was measured by fluorometry using the Qubit® dsDNA high-sensitivity assay kit and the Qubit® 2.0 fluorometer  as instructed by the manufacturer. DNA purity was also assessed by absorbance on a Nanodrop 2000  by measuring the A260/A280 ratio. Only DNAs with an A260/A280 ratio of 1.8–2.0 were used for PCR amplification (CTAATCC) . To multhttp://qiime.org/) with some modified methods. Chimeric sequences were removed using usearch61 [The 16S sequence paired-end data set was joined and quality filtered using the FLASH method described by Magoč and Salzberg . All seqsearch61  with de search61  within Qn = 6 voles/group). For the control group, saline (200 μL) was delivered by intragastric gavage to each animal. The recipients were still housed in separate cages at room temperature after CMT. Body weight and energy intake were measured during antibiotic treatment and within 1 week after CMT, and RMR and NST were determined 1 week after CMT. After the experiment, the voles were sacrificed and caecal contents were collected for 16S rRNA sequencing (n = 2–4/group) and SCFAs measurement.To remove microbiota, the healthy 4-month-old male voles were housed in separate cages at a room temperature (23 ± 1 °C) and were offered water with fresh composite antibiotics  for 7 days as described previously . For micTsurface, Tcore, the concentration of SCFAs, and microbial composition were analyzed by two-way ANOVA. Significant group differences were further evaluated using Bonferroni post hoc tests. All values were presented as mean ± SEM (standard error of mean), and P < 0.05 was considered to be statistically significant.The software SPSS 17.0 was used for statistical analyses. Prior to statistical analyses, all the data were examined for assumptions of normality and homogeneity of variance by Kolmogorov–Smirnov and Levene tests, respectively. The data with abnormal distribution were transformed by natural logarithms to normalize them. The data for body weight gain were transformed by arcsine and analyzed by two-way ANOVA (cold and huddling). Energy intake, RMR and NST were analyzed by two-way ANCOVA with body weight as a covariate. P values was done with Welch’s t test. The linear discriminant analysis (LDA) Effect Size (LEfSe) method was used to assess differences in microbial communities using a LDA score threshold of 2 [For microbiota data, to account for any bias caused by uneven sequencing depth, the least number of sequences present in any given sample from a sample category was selected randomly prior to calculating community-wide dissimilarity measures (α-diversity and β-diversity). We rarefied the OTU table to a sequencing depth of 12,000 per sample for both diversity analyses. All principal coordinate analyses (PCoA) were based on unweighted and weighted UniFrac distances using evenly sampled OTU abundances. Significance for PCoA (β-diversity) analyses was checked with multivariate permutation tests using the nonparametric method “ADONIS” (999 permutations) included in the package “vegan” of the QIIME-incorporated version of “R”. The boxplot representation of the α-diversity results was done with STAMP  and the old of 2 .Ta) tended to gain less body weight than those in warm . Body weight gain was not affected by huddling  or the interaction between cold and huddling . Energy intake was not affected by the interaction between cold and huddling .Body weight at the end (day 28) of acclimation was not affected by huddling or cold , but was not affected by the interaction between cold and huddling . RMR of huddling voles was 37% lower than in separated ones, both in cold (P < 0.001) and warm Ta (P = 0.05) , but was not affected by the interaction between cold and huddling . NST of CH voles was 31% lower than CS voles (P = 0.01), but was not different from WH voles (P > 0.05)  Fig. . The hud05) Fig. .Tsurface including Tm and Tp was affected significantly by huddling (P < 0.001), cold (P < 0.001) and their interaction  and cold (by 3.1 °C for Tm and 4.4 °C for Tp) conditions. Cold exposure resulted in lower Tm (by 4.6 °C in huddling and by 5.8 °C in separated group) and Tp (by 8 °C in huddling and by 10.4 °C in separated group) than in warm Ta. The Tc was 7.5 °C lower in cold huddling than in warm huddling voles .The Tcore dropped immediately both in huddling and separated voles. The separated voles in cold increased Tcore to the same level to the voles in warm, while the huddling voles continued to decrease Tcore  . The daily Tcore was not affected by the interaction between cold and huddling .In the first 2 days of exposure to cold, ore Fig. . After 101) Fig. . Tcore wP = 7.85e−4), whereas the effect of cold temperature on phylogenetic diversity was not significant (P = 0.938) , indicating distinctive microbial community structures in each group. The intragroup distances were significantly affected by huddling  and the interaction of huddling and cold , but not affected by cold .Huddling voles had a higher phylogenetic diversity (α-diversity) than separated voles (38) Fig.  and weig38) Fig.  UniFrac Firmicutes (76.9%) and Bacteroidetes (13.6%). Rare phyla included Spirochaetes (4.9%), Proteobacteria (3.2%), Cyanobacteria (0.6%), Actinobacteria (0.4%), and TM7 (0.1%) , Ruminococcaceae (23.1%), S24–7 (11.1%), Lachnospiraceae (10.9%), Spirochaetaceae (4.9%), and Lactobacillaceae (1.9%)  in voles included 1%) Fig. . Analysi9%) Fig. .Cyanobacteria, Tenericutes and TM7 at the phylum level, and of RF39, Rickettsiales, Comamonadaceae, and Sinobacteraceae at the order or family level, but increases in Lachnospiraceae and Veillonellaceae when compared with the separated voles , but decreased isovaleric acid concentration in warm  when compared with separated voles  and butyric acid in separated voles  when compared with warm conditions. The concentrations of propionic acid, isobutyric acid, and valeric acid were not affected by cold or huddling (P > 0.05). Total SCFAs were higher in cold than those in warm  and in huddling than those in separated voles . The isovaleric acid concentration was affected by the interaction between cold and huddling .The huddling voles increased acetic acid concentration in cold  or after CMT , but CMT from CS voles led to an increase in energy intake at day 3  and day 6 , butyric acid , isobutyric acid , and valeric acid  among groups . Huddling also resulted in decreases in energy intake, RMR, and NST in both warm and cold Ta. Both cold and huddling resulted in marked alterations in caecal bacterial composition at the phylum and family levels and also significant changes in microbial metabolites. Further, CMT indicated that huddling- or cold-induced variations in caecal microbiota regulate energy intake and metabolic rate of the host. These results suggest that the alteration in core temperature in the gut by huddling or cold may affect bacterial growth and activity and, hence, induce the observed changes in energy intake and thermoregulation.Huddling is a social thermoregulatory behavior in mitigating cold stress in endotherms. In the present study, we investigated the underlying coevolutionary and physiological mechanisms of huddling in regulating energy intake and thermogenesis from the new aspect of gut microbiota. We observed that huddling voles had higher Ta, mammals use many physiological mechanisms, including increased heat production, heat conservation, and energy intake [Microtus ochrogaster) [Microtus oeconomus) [Clethrionomys glareolus) [Microtus townsendii) [Rhabdomys pumilio) [To maintain normal body temperature under cold y intake . In smaly intake , 56, praogaster) , and rooconomus) . In the conomus) , short-tconomus) , bank voareolus) , townsennsendii) , and Afrpumilio) . BesidesTa. This was consistent with previous studies in mice (Mus musculus) [Ochrotomys nuttalli) [Phodopus sungorus) [Ta [a, however, the voles in cold would gain less body weight and/or body fat (data not shown) due to high metabolic costs, which was also found in the previous studies in voles [Ta of 23 °C used in this experiment was below the lower critical temperature. Therefore, huddling in warm group also had an energetic benefit.Due to the lower energy expenditure, the huddling voles consumed less energy than separated voles in both cold and warm usculus) , golden uttalli) , furred ungorus) , and socrus) [Ta . In contin voles , 43. Thein voles  and, theTcore over a wide range of Ta is a high evolutionary feature of endotherms [Tsurface compared with separated animals. Further, the increased Tsurface as warm resources may attract voles to huddle, especially in the cold.Maintenance of high and constant dotherms . Huddlindotherms , 67. TheTcore than separated voles, and CH voles had the lowest Tcore among the four groups. A similar result of lower Tcore under huddling has been recorded in birds where the goslings of greater snow geese (Chen caerulescens atlantica) in cold arctic environments had a Tcore by 0.3 °C when huddling [Tcore by 0.9 °C and increased local Tsurface during huddling in pair period in Antarctic winters [Tcore to the possible minimum set-point of body temperature. Moreover, the decrease in Tcore in response to a low Ta supports the importance of sensors of the thermal environment in determining the set-point to which Tcore is regulated [Tcore in huddling mostly came from the reduced metabolic rate in the present study and from previous studies [Tcore and temperature gradient between Tcore and Tsurface to reduce individual internal heat loss and conserve energy.We found that huddling voles had a lower huddling , and emp winters . We assuegulated . Other e studies , 69. TheApodemus sylvaticus) [Ictidomys tridecemlineatus) [Alouatta pigra) [Ochotona curzoniae) [Bos grunniens), and Tibetan sheep (Ovis aries) [Cyanobacteria, Tenericutes, TM7, Comamonadaceae, and Sinobacteraceae. Most of these are pathogenic bacteria and have been found to be associated with host inflammatory mucosal diseases [Lachnospiraceae and Veillonellaceae. The family Lachnospiraceae has been linked to protection from colon cancer mainly due to the production of butyric acid [Veillonellaceae was previously found in the intestinal microbiota of breast-fed infants [Gut microbial diversity is vulnerable to the environments of wild mammals. For example, seasonal variations in gut microbial diversity were reported in wild wood mice (vaticus) , ground ineatus) , and wila pigra) . Gut micrzoniae) , yaks (Bs aries) . We obsediseases , 73. Morric acid , 75. The infants  and in h infants , implyinTcore during cold exposure and in huddling in Brandt’s voles. Hibernating mammals exhibit an annual temperature rhythm [Phodopus roborovskii), and even humans show daily body temperature rhythm [Zootoca vivipara) [The shifts in caecal microbiota were associated with a reduction in e rhythm , 79 and e rhythm , 80. Mose rhythm , 82 and e rhythm , 84. A rivipara) . AlthougMicrobial metabolites, by interacting with enteric nervous system, provide the causal links between environment-induced alterations in gut microbiota and the physiological and behavioral responses of the host , 86. We In the present study, the changes in energy intake, RMR and NST were accompanied by variations in caecal microbiota during cold exposure and during huddling. In addition, the voles transplanted with CH microbiota had a lower energy intake and RMR than voles transplanted with CS microbiota, confirming that gut microbiota regulated energy intake and metabolic rate of the host. Further support was provided by the findings that cold microbiota transplanted to germ-free mice led to an increase in white fat browning and energy expenditure , 27. TheTcore. A healthier gut microbial community was detected in huddling than in separated voles which produced more SCFAs, particularly in cold Ta. Furthermore, CMT induced the alteration in energy intake, metabolic rate, microbial communities, and metabolites. These data demonstrate that the environment-associated reduction in host Tcore may change the gut microbial community, and the remodeling of gut microbiota and their metabolites mediate cold- and huddling-induced energy intake and thermoregulation and therefore orchestrates host metabolic and thermal homeostasis