One of Immanuel Kant’s best friends was Joseph Green, an Englishman who supposedly lived “by the clock”. Ford Doolittle is that kind of man. Ford will say things like, “I’ll pick you up at 10:25” and when you only make it at 10:27, you will feel an immediate urge to justify the delay. Ford, a tall, congenial emeritus professor of biology at Dalhousie University in Nova Scotia, had kindly invited me to come to a symposium he organized on ‘hype in science’ last December. Ford is famous for many things — most importantly, perhaps, for revolutionizing our concept of the tree of life. Ford championed the view that, at least in unicellular organisms, the tree is more like a network because these critters swap genes around quite happily, making the notion of separate branches somewhat obsolete. Recently, in honour of his many original and creative contributions to molecular evolution he received the Herzberg Medal, Canada’s most prestigious science award. The symposium was meant to look at cases where scientific findings have been oversold, misrepresented or misunderstood; how and why this happens; and what can be done about it (http://www.situsci.ca/event/hype-science). It was held by ‘situating science’, an initiative funded by the Canadian government that aims to bridge that much lamented cultural divide between sciences and the humanities. While such efforts can be a bit contrived at times, it worked exceptionally well in this case. There couldn’t have been a better person to kick off the symposium than Rosie Redfield, from UBC Vancouver. Rosie is a firecracker, with a fondness for unusual hair colours, and an avid blogger and twitteress. Most recently she became known for debunking [1Reaves M.L. Sinha S. Rabinowitz J.D. Kruglyak L. Redfield R.J. Absence of detectable arsenate in DNA from arsenate-grown GFAJ-1 cells.Science. 2012; 337: 470-473Crossref PubMed Scopus (96) Google Scholar] the extraordinarily hyped claim made in the pages of Science [2Wolfe-Simon F. Switzer Blum J. Kulp T.R. Gordon G.W. Hoeft S.E. Pett-Ridge J. Stolz J.F. Webb S.M. Weber P.K. Davies P.C. et al.A bacterium that can grow by using arsenic instead of phosphorus.Science. 2011; 332: 1163-1166Crossref PubMed Scopus (373) Google Scholar] that there were bacteria in Mono Lake whose DNA allegedly had a backbone linked by arsenate groups, rather than phosphate. The research was funded by NASA’s astrobiology program — a bizarre discipline that really doesn’t have anything to study so far, as there is no life in space that we know of. So instead, NASA funds research on earth, looking for a so-called ‘shadow biosphere’ — organisms that, so the assumption goes, are biochemically so different from ‘life as we know it’ that we haven’t managed to detect them. The arsenic bacteria would have been the first example of such a shadow biosphere and this was what got the media so excited; alas, as Rosie’s research has conclusively demonstrated, these bacteria are ordinary life forms based on phosphate-DNA and there’s nothing otherworldly about them. Among the many issues that came up in Rosie’s talk was PPPR (post-publication peer review) — the idea that, once they are published, peer-reviewed papers undergo a second round of scrutiny. Rosie has championed this idea and, in her case, it worked exemplarily well, although to this day the Science paper has not been retracted. To some degree, PPPR is of course nothing new — it’s what happens when people read and critique papers in discussion. But in the audience the idea of PPPR was enthusiastically received. Throughout the meeting, one got the sense that there is a widespread sentiment that the peer-review system is ‘broken’, although no one really could tell in precisely what way. Of course, the arsenic DNA is an example where peer review clearly did not work. Rosie showed the peer reviews that were made public, and indeed they were glowing. Rosie’s arsenic life debunking presents the most basic antidote for hype in science — hype tied to data in a paper, data falsified, hype goes away. The next case, presented by Ford Doolittle himself, was more complex. A little over a year ago, a flurry of papers was published reporting the fruits of a Big Science, multimillion dollar enterprise, rather grandiosely entitled the ‘Encyclopedia of DNA Elements’ — in short, ‘ENCODE’. The big news touted in the papers and the accompanying press coverage was that most (>80%) of the human genome was functional; thus, that old and somewhat demeaning concept of ‘junk DNA’, according to which most of the DNA in the genome has no direct information-carrying function, had itself become, well, junk. This had incensed Ford, perhaps not least because in the late 1970s he was one of the first to explain the existence of seemingly non-functional DNA. By that time, scientists had observed that the amount of DNA per nucleus in different kinds of organisms varies hugely (by a factor of 40,000) and in a way that isn’t correlated with the organism’s perceived complexity — a lungfish’s genome, for instance, is about 30 times larger than ours. The conclusion was that the genomes must contain a lot of uninformative DNA. Back to back with the molecular biology luminaries Leslie Orgel and Francis Crick, Ford and his grad student Carmen Sapienza had postulated that this was due to selfish DNA elements spreading in the genome. The human genome project then nicely corroborated this idea: most of our genome is indeed made up of such virus- and transposon-derived DNA. In his talk, Ford showed that the problem lies with the very loose set of definitions of ‘function’ that ENCODE had used for classing DNA elements. He used this as the peg for a philosophical excursion into what function can mean in biology. (I won’t give away too much as he is thinking about making this the topic of another symposium.) Ford reasoned that, even if we believe the ENCODE characterization and the human genome miraculously consists of only functional DNA, the problem won’t go away; the huge genome of the lungfish then would still have a ton of junk DNA (always assuming that the humble lungfish is not 30 times more complex than you and me and the people who ran ENCODE). So what if we did an ENCODE project on lungfish? Ford would predict that, because of the definitions of function employed, it would yield the same result of a high fraction of functional sites [3Doolittle W.F. Is junk DNA bunk? A critique of ENCODE.Proc. Natl. Acad. Sci. USA. 2013; 110: 5294-5300Crossref PubMed Scopus (275) Google Scholar]. A similar test, although much cheaper was proposed by Sean Eddy [4Eddy S.R. The ENCODE project: missteps overshadowing a success.Curr. Biol. 2013; 23: R259-R261Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar]: just synthesize a long stretch of random sequence DNA and let ENCODE see what proportion would turn up as functional. The experiment is probably underway, and a reviewer might perhaps have asked for it during peer review. In contrast to Rosie’s case, the problem with ENCODE wasn’t so much with the data themselves, which are surely valuable, but with the way they were interpreted, sold and lapped up by uncritical media. And thus, debunking is much less straightforward, though Ford’s published critique definitely did make some waves. The symposium was subtitled “How can respectable journals publish such cr∗∗”. So, as an editor for a journal that at least strives to be respectable, I should have been the prime addressee for that question. But Ford was kind enough not to put me on the pillory, and instead let me talk about epigenetics. And boy was I nervous, not least because some very eminent students of epigenetics, like the wonderful Brian Hall, were in the audience, all of which no doubt much more knowledgeable than me. Epigenetics, used widely in the loose sense of long-term, non-genetic effects on phenotype, is certainly surrounded by a lot of hype. Unlike the ENCODE kerfuffle, which seems to have ebbed away, the hype around epigenetics, which is based on similar misunderstandings of what constitutes ‘function’, looks as though it’s here to stay. Epigenetics is a vast area touching on things as diverse as twin studies, genetic determinism, inheritance of acquired traits, DNA modification, transcription and development. My thesis was that the hype around epigenetics (or the distorted version thereof) is a ‘perfect storm’ as epigenetics is being hyped both inside and outside science for different reasons: the immense interest in epigenetics in the public — there’s even an epigenetics beauty company — comes from the fact that it touches on a very essence of the human sense of agency (much like ‘free will’ does in neuroscience). The idea that your genes can determine your destiny makes people uneasy. The notion that, via so-called epigenetic changes, one’s lifestyle can change that destiny conveys a sense of empowerment that seems to resonate well with people. Within science, things are different. There, as with ENCODE, the main drive for the rise of epigenetics was the urge to assign an informational instructive role (cf. the histone code) to the many chromatin modifications discovered in the last three decades. In molecular biology, something that plays an informational/instructive role is infinitely more sexy than a permissive or structural role. So far, the jury is out whether systems commonly (and sloppily) called ‘epigenetic’, such as DNA methylation or histone modification, really play an instructive role. And of course, we already had a very good understanding of how gene activity is regulated before the so-called ‘epigenetics revolution’ came along. Partly as a nod to the humanities people in the audience, I made an excursion into the history of the concept of epigenetics — the term was coined by Conrad Hal Waddington with a meaning that no one uses anymore, Waddington’s epigenetics is nowadays called developmental biology — and tried to argue that this shifting meaning of epigenetics is what made it so liable to become a buzzword for hype [5Maderspacher F. Lysenko rising.Curr. Biol. 2010; 20: R835-R837Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 6Ptashne M. Epigenetics: core misconcept.Proc. Natl. Acad. Sci. USA. 2013; 110: 7101-7103Crossref PubMed Scopus (137) Google Scholar]. Finally, I discussed some examples of induced heritable changes in phenotype. Luckily, just that week a paper had appeared describing such an effect in mice where learned sensitivity to an odour can be inherited into the next generation. Need I say that the media hyped this as “your fears can be transmitted to your grandchildren”, because the authors had used a standard fear-conditioning assay to train the mice and test sensitivity. My conclusion was that, while interesting biology in their own right, these examples don’t necessitate a new evolutionary theory, let alone a Neo-Lamarckian one. Although my 60 or so slides had quelled the will to live (and ask questions) in nearly everyone, I got some interesting criticism, for instance regarding the many researchers who strongly advocate an epigenetic memory of lifetime experiences and the meaning of the code metaphor. A very nice gentleman in the audience remarked that Hegel, had he had PowerPoint slides like mine at his disposal, would have made a much larger impact (at least that’s what I think he meant and I took it as a compliment; though it’s perhaps a good thing Hegel didn’t have PowerPoint). In a simplistic (and long-obsolete) world view, where nature was set vs. nurture, I suppose the last talk of the day could have been construed as the antithesis to mine, as it did to simplistic genetic determinism what I tried to do to epigenetics. In it, the Harvard professor of the History of Science and of Studies of Women, Gender, and Sexuality, Sarah Richardson took apart a pair of papers, Bruce Lahn and consorts published some years ago [7Evans P.D. Gilbert S.L. Mekel-Bobrov N. Vallender E.J. Anderson J.R. Vaez-Azizi L.M. Tishkoff S.A. Hudson R.R. Lahn B.T. Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans.Science. 2005; 309: 1717-1720Crossref PubMed Scopus (368) Google Scholar, 8Mekel-Bobrov N. Gilbert S.L. Evans P.D. Vallender E.J. Anderson J.R. Hudson R.R. Tishkoff S.A. Lahn B.T. Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens.Science. 2005; 309: 1720-1722Crossref PubMed Scopus (336) Google Scholar]. The papers reported that two genes (microcephalin and ASPM) underwent recent positive selection in humans. These two genes are mutated in a human condition known as ‘microcephaly’ where the cerebral cortex is smaller. What set the alarm bells ringing was the papers’ claim that selection took place only in humans that had left Africa, which of course presented to the authors an irresistible incentive to speculate about cognitive evolution in modern humans after the Out-of-Africa migration. I remember when these papers came out, bemoaning with a colleague the simplistic notion that a gene that causes small brains when non-functional would be implied to be able to underlie cognitive evolution. At the molecular level, the function of these two genes is not that of your typical developmental regulator: one of them is part of the DNA repair machinery, the other part of the mitotic spindle, so from a functional point of view it is hard to see how these genes can ‘underlie’ brain development. In all of the follow-up studies, none of the presumed selected variants could be found to be associated with any sort of cognitive advantage. What’s more, even the claim that these genes were under positive selection was refuted. Had these genes been, say, blood-clotting factors with positive selection in Inuit, “the juggernaut of science” (Ford Doolittle’s term) would have shrugged and moved on. But because the link between positive selection out of Africa and brain development genes could be (and in some places was) construed as silently implying that Africans have less evolved brains than the rest of us, the hype surrounding this research was of course more dangerous. Sarah Richardson set this story against previous claims about the statistical distribution of IQ, which never made it into the scientific mainstream, because they were methodologically easily refuted. In her interpretation, post-genomic science, which combines human genetics with functional studies, is in its individual sub-disciplines methodologically more accepted, which makes these studies harder to debunk. She urged that studies in this multidisciplinary context require a more rigorous scrutiny and contextualization. What wasn’t quite clear to me was whether Sarah thinks that in principle possible cognitive differences between humans deserve investigation or not. From a genetic point of view, I think many biologists would be surprised if there wasn’t some genetic basis to cognition in humans, and if consequently there wasn’t a difference between and within human populations. Sarah contrasted the level of evidence for microcephaly genes with that for the well-established case of lactase persistence, which has been selected for in human pastoralists. From a purely population genetic point of view, the comparison makes sense, but it seems tricky when function is considered. In the lactase case, the expression of the enzyme is pretty much the entire phenotype, whereas the development of the human brain and its function is a much more complex process, making inferences from gene to phenotype more entangled and indirect. Some people also felt that it was worth mentioning that genetics has actually played a crucial and positive role in clarifying the degree and pattern of variation in human populations, and thus was instrumental in doing away with the old concept of human races, at least in the sense of deeply separated, genetically distinct clades. Potential racism is a serious issue, no doubt, but the most serious implication of hyped-up science (or pseudoscience) is when human lives are at stake. Dalhousie’s former Dean of Medicine Jock Murray gave thus in many ways the most impressive talk of all. He reported on how a vascular surgical therapy for multiple sclerosis (‘liberation therapy’), which aims to increase blood flow to the brain, became hyped for its alleged healing successes. Liberation therapy — the name itself reeks of propaganda — has since led to the death of several patients from complications. This makes the “tweed-jacket wars” (Jock’s term) over epigenetics or arsenic DNA seem rather petty. Medicine has very rigorous criteria for what constitutes a valid clinical trial, and Jock convincingly explained that the trial for liberation therapy should have never been published. So, here, the scientific journal, a medical journal, failed, allegedly because they deemed the importance of the issue more pressing than upholding the standards of clinical trials. Once the cat was out of the bag, a storm broke loose: patient groups, especially in Canada, lobbied for this therapy to be made available, and when it wasn’t, private ‘medical tourism’ companies stepped in offering the procedure anywhere from Costa Rica to Poland. Multiple sclerosis is a mysterious, incurable chronic disease that takes a great toll on patients and their families. So, it’s perhaps understandable that people will clutch at any straw. But the problem is not only that this therapy doesn’t help, it is positively dangerous. Once the cat is outside the bag, it’s been almost impossible to put it back in. And at one stage, multiple sclerosis experts were too afraid to speak out against this therapy in front of patient assemblies — at which point Jock, whose calm manners command immediate respect, stepped in and enlightened them. At the end, the big question of “what can be done?” was put to the speaker panel. As you won’t be surprised to hear, despite lively and interesting discussion, no answer was arrived at. At one point, I tried to play devil’s (read: journals’) advocate in response to a comment from the audience suggesting we should get rid of all the science journals with glossy covers (disclaimer: one such pays my bills). I suggested that not all hype was bad and that getting the public engaged in science was part of the deal of doing science. Sarah put forward the idea of a ‘slow science’ movement, where the often breathless rat race is slowed such that its results can actually be digested before they are disseminated (she phrased it much better!). Rosie encouraged everyone to go out and tweet and blog and contribute to Wikipedia, in order to debunk and educate. The next day, Ford picked me up at the hotel. I was two minutes late, but he said that it didn’t count as he himself wasn’t there on time. Ford, who I learned is also an enthusiastic photographer in the William Eggleston tradition, took me on a drive out to Peggy’s Cove, a wonderful landscape of rolling granite bedrock hills, with very sparse tundra-like vegetation. Among the hills, big erratic blocks were scattered, just where the glaciers had dropped them, a few millennia ago. An eerie, timeless landscape, as if the last ice age has just passed. For lunch, we had delicious fish and chips, entirely hype-free.