Marzieh Ghiasi and Madhukar Pai from McGill University & McGill International TB Centre, Montreal, review “The Remedy” by Thomas Goetz
Robert Koch raised the hopes of millions of tuberculosis patients with his remedy (i.e. tuberculin) that turned out to be ineffective. Today, tuberculin is a widely used diagnostic test for latent tuberculosis infection (picture). Image credit: Madhukar Pai
No image is more iconic of the Victorian age than that of a detective with a deerstalker cap, pipe, and magnifying glass roaming the dark streets of London in search of criminals and murderers. Hidden in plain sight, the real killers of the nineteenth century were infectious diseases such as tuberculosis, responsible for as many as a quarter of all deaths in that era.
In The Remedy (2014) science journalist Thomas Goetz recounts the stories of Robert Koch, the founder of modern bacteriology, and Arthur Conan Doyle, the physician-author of the Sherlock Holmes series. In two narratives that run in parallel and eventually intersect, Goetz introduces a cast of pioneering medical detectives, from Koch’s scientific rival Louise Pasteur, to Conan Doyle’s inspiration for Sherlock Holmes, Joseph Bell. We follow a search for causative agents, preventive vaccines, and remedies for some of the deadliest infections in the Victorian era. Goetz describes how the principles of evidence-based science and systematic experimentation guided these ground-breaking discoveries, and how overlooking these principles led to setbacks.
Anastasia Koch, a molecular biology PhD student in South Africa talks about engaging the community with biomedical research.
Lwazi Fanana, Ndilisa May, and Monwabisi Mkungela from Ikamva Youth visit MMRU labs
Image credit: EH!WOZA 2013
As a molecular biology – molecular mycobacteriology to be precise – PhD student, I never thought I’d be involved in the production of documentaries & online media resources. In the past few months, I’ve uncharacteristically found myself critiquing aesthetics in film and design owing to an involvement in a unique collaboration between biomedical scientists, artists, and a community not-for-profit organisation.
Let me begin with some background. I work in the Centre of Excellence for Biomedical TB Research (CBTBR) of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town. My PhD research is focused on understanding the molecular determinants (and associated physiological implications) of drug resistance in Mycobacterium tuberculosis, the bacterium which causes tuberculosis (TB).
Post doc Collin Diedrich discusses his experiences as a learning disabled scientist.
Image credit: Collin Diedrich
About a month ago, I was playing with my 3yr old niece, drawing pictures with Crayola Crayons. She pulled out a purplish color and asked me what it was. I dutifully read the name, as phonetically as I could, “MAG-A-NEAT-A… what the hell is MAG-A-NEAT-A?” We all laughed, and my brother (the dad) intervened: “It’s MA-GEN-TA.” I told my niece I probably am not the best person to read her these names. Also that I should learn to use better language around 3yr olds.
I read between a 6th and 9th grade level and have a language processing speed in the bottom 14% of the population. I have an unspecified reading disorder (DSM-IV 315.00) and learning disorder (DSM-IV 315.9). Despite these learning disabilities (LDs) and my love-hate relationship with Crayola Crayons, I have a PhD in molecular virology and microbiology and I am a second-year post doc at University of Cape Town. My life is not a mental contradiction.
Geneviève Lanotte (retired), Jean-Antoine Rioux (retired), and Jérémy Bouyer from CIRAD recount that cellular fusion in Leishmania was filmed in the 80s and provide the sex movie to the scientific community.
The title of our comment refers to the humorous title of the Review by Rougeron et al. (2010) on the sexuality of Leishmania: Everything You Always Wanted to Know about Sex (but Were Afraid to Ask)” in Leishmania after Two Decades of Laboratory and Field Analyses. In this paper, the authors present recent works challenging the dogmatic hypothesis of “dominant and ancient clonal reproductive mode”. Amazing animations already exist to illustrate the clonal reproduction cycle of Leishmania. Rougeron et al. (2010) refer to population genetics and experimental works but point out the “lack of clear evidence (experimental or biological confirmation) of sexuality in Leishmania parasites” and suggest using high-resolution imaging to capture a mating event. But what if a sex movie was already available?
The sexuality of Leishmania: from fornicomastigotes (on the left) to a zygomastigote (on the right), recorded in the late 80s by Lanotte & Rioux. The full video is provided for the first time at the end of this comment.
Before satisfying our curiosity, let’s revisit some concepts.
c/o Sense About Science
14A Clerkenwell Green
London EC1R 0DP
Professor Guido Rasi
Director, European Medicines Agency
7 Westferry Circus
London E14 4HB
2nd June 2014
Dear Professor Rasi
Re: Draft Publication and access to clinical-trial data policy (EMA/240810/2013)
Hundreds of supporters of the AllTrials campaign contributed last year to the Agency’s consultation on its draft policy “Publication and access to clinical-trial data.” We welcomed the EMA’s proposals which would have seen Clinical Study Reports published proactively and openly in line with an Agency policy that the information in those reports should not generally be considered commercially confidential. We are now concerned that the most recent draft of the policy as shared with some stakeholders at meetings this month introduces barriers that will make it all but useless to independent researchers.
We understand that there are four areas of particular concern:
1. Clinical Study Reports will only be available for viewing on screen and cannot be saved, downloaded, printed, copied, annotated or shared in any way. This will make it nearly impossible for researchers to usefully scrutinise the documents. CSRs often contain thousands of pages of complex information. Research teams need to be able to share information and researchers have to be able to print or copy information such as outcome definitions, to make valid comparisons across studies. Your policy on access to CSRs as initially proposed could have made a genuine contribution to medical research. It now risks becoming a superficial and practically useless gesture.
2. The wording of the draft “Redaction Principles” policy is ambiguous, and where there is ambiguity, there is likely to be excessive redaction. For example, “statements/descriptions relating to objectives that are not supportive of a label claim and do not contribute to the overall benefit/risk evaluation” may be redacted. This would appear to suggest that any information on off-label uses of drugs will not be made available. While the Agency’s own use of these documents may be limited to a decision on one specific use of a treatment, in everyday clinical practice these same treatments are routinely and legally used by clinicians outside their marketing authorisation. This prescribing is based on published evidence that may be particularly vulnerable to dissemination bias, since evidence on off-label uses is frequently excluded from even voluntary codes of practice.
3. The “Redaction Principles” policy asks sponsors to submit two versions of a CSR from each trial: a standard version (CSR(a)) and a redacted version (CSR(b)). While this might be driven by a desire to lower the costs of transparency for the Agency, it puts primary responsibility for redacting in the hands of sponsors. How close CSR(a) is to CSR(b), and which parts are missing, may never be known to researchers granted access to CSR(b). Will there be an audit to explore whether redactions are proportionate or risk patient safety, and penalties for excessive redactions?
Elspeth K. Ritchie from Newcastle University’s Biopharmaceutical Bioprocessing Technology Centre reflects on discussions between academic journal editors and writers after attending the Voice of Young Science “Peer Review: Nuts & Bolts” workshop, which was supported by several organisations including PLOS.
The words “peer review process” mean different things throughout a scientist’s career. For the established professor, it may be a well worn path. Meanwhile, it strikes terror into those preparing to submit for the first time. For those wanting to manage that fear by better understanding the process, events such as the Voice of Young Science “Peer Review: The Nuts & Bolts” workshop are highly recommended.
Image Credit: Justin Taylor, Flickr
Peer Review: Nuts & Bolts
Assembled at Guy’s Campus, King’s College London was a varied cross‑section of persons involved in peer review. A guest panel of editors represented nearly all aspects in the post‑submission peer review process: Dr Elizabeth Moylan, Professor John Gilbert, and Alice Ellingham.
Praveen Aivalli presents some reflections about the neglected status of the elderly in India, and the need for an organised health system response to tackle this issue.
Image Credit: Adam Jones, Flickr
A hundred and two year old man lying helpless in the corner of a house like an animal raised a question in my mind about the situation of Indian elderly in rural India. I came across this old man at a village of south Indian state Karnataka. The man was once the head of the family, and its sole breadwinner, and today he lies in a corner of the house, abandoned by his family. A man who had built this house, provided for his children, played his role in society and perhaps never imagined that he will be spending his last days in a cow shed he made, just waiting the end.
I visited his village as part of a research team collecting data on access to medicines for rural poor. While I was talking with his family members, he turned his head towards me and waved his hand. Out of interest I went inside the room to see his condition. He only noticed my presence through my voice; I saw that he was feeling things around him with his hands, and continued waving his hands in my direction. I was unable to understand his gestures. I peered closely only to notice his glazed eye caused by hyper-mature cataract; I wondered how long he had been blind. I couldn’t talk to him as he was unable to hear me and I was unable to understand his expressions, but one thing I heard very clearly “maatrekodi” (“give me medicine” in Kannada, the local language). He was asking me for the tablets for his body ache.
Trisha Greenhalgh discusses classic ethnography texts and their applicability to health services research.
Ethnography is, traditionally, the remit of anthropologists. Think mud huts and pith helmets: months or years living among the ‘natives’, immersed in the strangeness of a distant culture and producing what Clifford Geertz called thick description . More recently, ethnography has been appropriated by both management academics and health services researchers to study the culture of organisations [2-4].
In general, doctors are not trained in anthropology – or indeed in other interpretive methods. The methodology has become distorted and over-rationalized by medically trained researchers whose criteria for excellence have been appropriated from the randomized controlled trial. They may wrongly equate rigour with the use of structured checklists of what to observe, how, and for how long – or for two researchers to make independent observations of the same phenomenon on the assumption that they should both come out of the experience with the same set of ‘facts’. In reality, ethnography draws extensively on subjective methods and rigour is as much about reflexivity (self-questioning) and criticality (considering alternative explanations) as about accuracy or reproducibility of measurement .
Image Credit: Fotos GOVBA, Flickr
In November 2013, PLOS Medicine and the Maternal Health Task Force (MHTF) called for submissions to Year 3 of the MHTF-PLOS Collection on Maternal Health. Today we launch the Year 3 Collection and include 10 research articles recently published by PLOS.
Image credit: Jack Zalium, Flickr
The continuing collaboration between the MHTF at Harvard School of Public Health and PLOS Medicine is reflected in this latest collection highlighting the theme, “Integrating Health Care to Meet the Needs of the Mother–Infant Pair”. Our shared commitment to increasing the evidence base for approaches to improving maternal health has built a platform of research and commentary articles as featured in the preceding Year 1 & Year 2 Collections.
Trudo Lemmens of the University of Toronto critiques the recently distributed draft EMA Clinical Trials Data Release Policy.
Image Credit: r2hox, Flickr Commons
Things were looking good recently in Europe for data transparency, a necessary, albeit not sufficient, tool to promote integrity of pharmaceutical data. The European Court’s Vice-President overturned in November 2013 two lower court interim suspensions of EMA’s data access decision in relation to Abbvie’s drug Humira and Intermune’s Esbriet, which had stalled EMA’s data release approach. Shortly after, Abbvie withdrew the Humira lawsuit. Then in April 2014, the European Parliament approved the new Clinical Trials Regulation that introduced a requirement to register all clinical trials and make all clinical study reports in relation to EMA approved drugs publicly available. These developments put EMA again in the driver’s seat for the further implementation of its promised prospective data release policy.