‘Translation’ – from mouse to human and back – the mantra and eternal quest of university medicine! Where else than in academic medical centers can you find all this under one roof: basic biomedical and clinical research, the patients necessary for clinical trials, government funding, as well as motivated and excellently trained personnel! ‘Translation’ is as old as academic medicine itself – but the term for it was only coined in the 1980s and since then it has adorned the websites and mission statements of all university hospitals worldwide. Translation has certainly been a model of success – just think of, treatment of chronic neurological disorders like epilepsy, Parkinson’or multiple sklerosis, therapies of some forms of cancer, or HIV. Continue reading
(Update August 2020)
On March 17th, just as many countries were taking draconian measures to contain the SARS-COV-2 pandemic, the Greek-American meta-researcher and epidemiologist John Ioannidis, whom I often quote in my posts proclaimed a “fiasco in the making‘! With strong language and a few ad hoc estimations of COVID fatality rates he warned that based on poor data or no evidence at all politicians might inflict incalculable damage on society, possibly much worse than what a virus, putatatively as dangerous as influenza, could cause. As one of the most highly cited researchers in the world and a vocal critic of quality problems in biomedicine, his COVID related interviews, opinion pieces and articles since then have received a great deal of attention, in the scientific community, in the lay press, and especially among his worldwide fan base. Continue reading
Research using animals is a sensitive issue. Anyone who does animal experiments, like myself, is reluctant to talk about it, at least outside our natural habitat, the laboratory or scientific conventions. Institutions where animal experiments are carried out are also quite shy about the topic. Recently, the Max Planck Society left Nikos Logothetis (MPI Tübingen) standing in the rain when he was targeted by a media campaign. Now he and some of his laboratory staff are off to Shanghai… The websites of prominent research institutes feature all kinds of colorful illustrations showing immunohistochemistry slides, doctors and students in white coats with pipettes in their hands, sitting at computers or their microscopes. But rats or mice are conspicuously missing! They proudly display their research activities, and enthusiastically advertise (future) research breakthroughs towards completely new and effective therapies. But no reference is made to animal experiments on campus!
You got to see this youtube video! Hectically cut sequences of busy young scientists in high-tech laboratories wearing lab coats, nerdy looking guys are soldering electronic circuits and stare into oscilloscopes, we are taken on a roller coaster ride through an animated brain chockful of tangled nerve cells. And in between all this, on stage at the California Academy of Sciences, car and rocket manufacturer Elon Musk announces his latest vision in a messianic pose: The symbiosis of the human brain with artificial intelligence (AI)! This time his plan to save mankind does not involve mass evacuation to Mars, but will be realized by a revolutionary Brain Machine Interface (BMI), designed and manufactured by his company Neuralink. You may have guessed it, this has caused a tremendous media hype all over the world. The verdict in the press and on the net was: “Musk at his best, a bit over the edge, but if HE announces a breakthrough like that there must be something to it”. The more cautious asked: “But couldn’t this be dangerous for mankind? Do we need a new ethic for stuff like this?” Continue reading
Recently in a train station book shop I stood gaping in astonishment in front of a thematically highly specialized book display. It was the bowels-brain table. The books piled up on it promised enlightenment about how the bowel and in particular its contents influence us – yes – how, they verily steer our emotions. A selection of book titles: “Shit-Wise – How a Healthy Intestinal Flora Keeps us fit”; “Bowels heal brain heal body”; “Happiness begins in the bowels”, or “The second brain – How the bowels influence our mood, our decisions and our feeling of wellbeing”. Newspapers, magazines and the internet can also tell us this. The wrong bowel bacteria make us depressive – but the right ones make us happy … which is why yogurt helps against depression. Continue reading
U.S. economist Robin Hanson posed this question in the title of an article published in 1995. In it he suggested replacing the classic review process with a market-based alternative. Instead of peer review, bets could decide which projects will be supported or which scientific questions prioritized. In these so-called “prediction” markets, individuals stake “bets” on a particular result or outcome. The more people trade on the marketplace, the more precise will be the prediction of outcome, based as it is on the aggregate information of the participants. The prediction market thus serves the intellectual swarms. We know that from sport bets and election prognoses. But in science? Sounds totally crazy, but it isn’t. Just now it is making its entry into various branches of science. How does it function, and what does it have going for it? Continue reading
- Let’s get this out of the way: Reproducibility is a cornerstone of science: Bacon, Boyle, Popper, Rheinberger
- A ‘lexicon’ of reproducibility: Goodman et al.
- What do we mean by ‘reproducible’? Open Science collaboration, Psychology replication
- Reproducible – non reproducible – A false dichotomy: Sizeless science, almost as bad as ‘significant vs non-significant’
- The emptiness of failed replication? How informative is non-replication?
- Hidden moderators – Contextual sensitivity – Tacit knowledge
- “Standardization fallacy”: Low external validity, poor reproducibility
- The stigma of nonreplication (‘incompetence’)- The stigma of the replicator (‘boring science’).
- How likely is strict replication?
- Non-reproducibility must occur at the scientific frontier: Low base rate (prior probability), low hanging fruit already picked: Many false positives – non-reproducibility
- Confirmation – weeding out the false positives of exploration
- Reward the replicators and the replicated – fund replications. Do not stigmatize non-replication, or the replicators.
- Resolving the tension: The Siamese Twins of discovery & replication
- Conclusion: No scientific progress without nonreproducibility: Essential non-reproducibility vs . detrimental non-reproducibility
- Further reading
There is a lot of thinking going on today about how research can be made more efficient, more robust, and more reproducible. At the top of the list are measures for improving internal validity (for example randomizing and blinding, prespecified inclusion and exclusion criteria etc.), measures for increasing sample sizes and thus statistical power, putting an end to the fetishization of the p-value, and open access to original data (open science). Funders and journals are raising the bar for applicants and authors by demanding measures to safeguard the validity of the research submitted to them.
Students and young researchers have taken note, too. I teach, among other things, statistics, good scientific practice and experimental design and am impressed every time by the enthusiasm of the students and young post docs, and how they leap into the adventure of their scientific projects with the unbent will to “do it right”. They soak up suggestions for improving reproducibility and robustness of their research projects like a dry sponge soaks up water. Often however the discussion is in the end not satisfying, especially when we discuss students’ own experiments and approaches to research work. I often hear: “That’s all very good and fine, but it won’t get by with my group leader.” Group leaders would tell them: “That is the way we have always done that, and it got us published in Nature and Science”, “If we do it the way you suggest, it won’t get through the review process”, or “We then could only get it published in PLOS One (or Peer J, F1000 Research etc.) and then the paper will contaminate your CV”, etc.
I often wish that not only the students would be sitting in the seminar room, but also their supervisors with them! Continue reading
I failed to reproduce the results of my experiments! Some of us are haunted by this horror vision. The scientific academies, the journals and in the meantime the sponsors themselves are all calling for reproducibility, replicability and robustness of research. A movement for “reproducible science” has developed. Sponsorship programs for the replication of research papers are now in the works.In some branches of science, especially in psychology, but also in fields like cancer research, results are now being systematically replicated… or not, thus we are now in the throws of a “reproducibility crisis”.
Now Daniel Fanelli, a scientist who up to now could be expected to side with those who support the reproducible science movement, has raised a warning voice. In the prestigious Proceedings of the National Academy of Sciences he asked rhetorically: “Is science really facing a reproducibility crisis, and if so, do we need it?” So todayon the eve, perhaps, of a budding oppositional movement, I want to have a look at some of the objections to the “reproducible science” mantra. Is reproducibility of results really the fundament of scientific methods? Continue reading