The Journal: The Instrument that Shapes Science and Academia

Anna Gielas traces the history of the journal, and it's essential role in research and scholarship. Image courtesy of Tom Blackwell, Flickr.

Anna Gielas traces the history of the journal, and it’s essential role in research and scholarship. Image courtesy of Tom Blackwell, Flickr.

By Anna Gielas

No matter whether you study medicine or biology, law or art, neuroscience or history — there is one instrument that we all share: the journal. Learned journals play a pivotal role in science and academia. Publishing in scholarly periodicals disseminates our insights and bolsters scientific communities. It propels careers and fosters knowledge. And if this knowledge can be applied practically, then the academic journal renders a service to society.

But why does all this happen specifically through the journal? Why not through newspapers, newsletters, catalogues, tables, graphs, a collection of abstracts, private correspondence, pamphlets or monographs? When I pose these questions to academics of different disciplines and career stages, I usually receive the same answer: “Probably because the journal has been more efficient than these alternatives.” But who has made it more efficient and how? Who has deemed it more efficient and why? In short: how did the academic journal become such an essential part of our professional lives? The answer is simple: we do not know. At the core of our scientific and scholarly endeavor we find the journal — and we cannot explain why.

The history of the academic journal is tricky. I already need to be careful when using the term “academic journal”: at the time when first learned periodicals appeared, the pursuit of insight and knowledge took place in a fundamentally different framework than it does today. Back then, the periodical had but a few links to universities. If we want to understand the historical development of the journal, we need to understand the development of science and academia — and a myriad of other elements such as the evolution of publishing technology and postal services.

The saintly approach

Historians of science have already disentangled some parts of the journal’s history and established several milestones. We know, for example, that the earliest learned periodicals appeared in the second half of the seventeenth century. They were not celebrated as helpful innovation. Instead they met some skepticism, both within and without scholarly communities. The German journal Acta Eruditorum (1682 – 1782), for example, ended up on the Catholic Church’s Index of Prohibited Books.

To appease ecclesiastical authorities, some of Acta‘s avid proponents argued that scientific editing had commenced with Saint Photios the Great (c. 810 – c. 893). As the leader of the Eastern Orthodox Church and a central thinker of the Byzantine Renaissance, Photios I seemed the common denominator between the men of church and the men of science. But the Germans had little luck with their claim: Acta appeared on the Index for (at least) 72 consecutive years.

Despite clerical disapproval, Acta‘s editors established a fine balance. On the one hand, they selected content that would prompt neither ecclesiastical nor secular powers to forbid the publication for good. On the other hand, they managed to make the contents so worthwhile that men of science throughout Europe would laud the publication.

We could assume that once the learned journal was introduced, its popularity would slowly increase. But for almost 100 years there was not much interest to publish more such periodicals. The interplay of reasons causing this apparent hiatus have not been established yet. There is currently also no explanation for why journals started to burgeon in the 1770s — and have, apart from some minor interruptions, been doing so ever since.

We are currently learning more and more about the peer review, which was formally introduced in the 1830s. It became a required gateway for the Philosophical Transactions, the oldest science journal still in print (f.1665). We cannot rule out the possibility that some editors used peer review at an earlier point. But we can say for sure that this practice did not commence with the first journals in the seventeenth century. Every procedure surrounding the scientific periodical and each of its elements — including the articles, footnotes, reviews, and abstracts — evolved over time.

Into the unknown

The scientific journal has been — like every other invention — a malleable instrument whose development is marked by trial and error. These errors could mean financial ruin and devastation. During 300 years since the first science journals came out, merely a few commercial editors made notable wins instead of losses. Periodicals that, in turn, were edited by learned societies—like the Philosophical Transactions published by the Royal Society — tended to be in the red. Oftentimes these journals were not supposed to bring in profit but prestige. By publishing the most important findings and announcing inventions, a society could assert its central role in the scientific endeavor. Other editors had different incentives. Editing a journal could for example secure the attention of a future patron, someone who would finance the editor’s research. Or, as was the case in eighteenth-century Germany, authorities took notice of learned periodicals and recruited their editors for civil service.

Since then, some reasons for editing academic journals have changed drastically, while some motives have remained unaltered. One of the latter is the wish to contribute to science. Last year, more than 90,000 PLOS volunteers reviewed 33,000 articles. PLOS currently publishes seven journals. To put things in perspective: these are seven out of 30,000 peer-reviewed journals world-wide. I wish to learn how we have created this unique and intricate communication system — and why we have endowed it with so much power.

References:

William Clark: Academic Charisma and the Origins of the Research University. University of Chicago Press, 2007.

Aileen Fyfe: Journals and Periodicals. In:A Companion to the History of Science, edited by Bernard Lightman, Wiley/Blackwell, 2015.

Index Librorum Prohibitorum. Nabu Press, 2010.

David Kronick: History of Scientific and Technical Periodicals: The Origins and Development of the Scientific and Technical Press, 1665-1790, Scarecrow Press, 1962.

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WHO will lead and who will pay? The World Health Organization, Ebola and the future of global health

Dr Margaret Chan, WHO Director-General addresses during the 67th World Health Assembly, Palais des Nations, Geneva. Monday 19 May 2014. Photo by Violaine Martin

Dr. Margaret Chan, WHO Director-General addresses the UN during the 67th World Health Assembly, Palais des Nations, Geneva. Monday 19 May 2014. Photo by Violaine Martin

By Andreas Vilhelmsson
When the Ebola virus disease epidemic hit West Africa in late 2013, nobody could imagine that just a year and a half later it will have caused more than 11,000 deaths and be declared a threat to international peace and security. The outbreak overwhelmed the world. Building on this experience, the World Health Organization (WHO) recently announced that it would create a new programme for health emergencies, uniting outbreak and emergency resources. Dr. Margaret Chan, the Director-General of the WHO,  announced plans to complete these changes by the end of the year in her opening speech at the Sixty-eighth World Health Assembly. Chan is also calling for a new US$100 million contingency fund to finance the health emergency programme.

This announcement was a direct response to the harsh criticism of weak leadership the Organization received in the aftermath of the outbreak. Among other things, the WHO has faced criticism for the slow international response to the epidemic and a weak leadership overall. One of the strongest critical voices belonged to Médecins Sans Frontières (MSF) who referred to “a vacuum of leadership” in the WHO, leaving them to deal with the Ebola virus in West Africa almost single-handedly — a virus that WHO should have been fighting.

A fragmented budget
The global scale of the Ebola outbreak, argue Gostin and Friedman in a recent article in the Lancet, is the type of moment for which the WHO was created. But instead, the Ebola crisis revealed fragile national health systems and a fragmented global health response system, with WHO falling short of its leadership responsibilities.

But does this really come as a surprise?

Today, only 25 percent of WHO’s biennial programme budget comes from assessed contributions, while the remainder comes from voluntary funds that are largely restricted for purposes specified by donors. In the wake of the global financial crisis, the Organization has been forced to endure austerity cuts and most of its budget now depends on these voluntary contributions. The truth is that WHO is inadequately funded to deal with threats like Ebola.

And here is the catch with the WHO-proposed contingency fund. The call for US$100 million may sound good, but it will be financed by flexible voluntary contributions. Funding by flexible voluntary contributions raises concerns if it will actually raise the money needed in the end, or if it will falter under the obligatory promises donors make when they are in the spotlight. Competition for donor funds between the WHO Health Emergency Programme and other global commitments is a real possibility. For example, the COP21 climate summit in Paris in December is approaching, and the need for new donor pledges to reach a global climate deal. Despite the new health emergency programme, Ebola still risks becoming “yesterday’s news”.

Public-Private Partnerships
The contingency fund will also be built on partnerships with other organizations, ranging from UN agencies or NGOs like MSF. Today, these different collaborative efforts are often formalized in a large number of public-private partnerships (PPPs). These partnerships may be formed by cooperation between the global health sector (e.g. WHO) and NGOs (e.g. MSF) in dealing with health emergencies like Ebola, but can also involve private organizations in an effort to raise large amounts of financial resources for a particular disease or cause (e.g. Gavi). In some cases, the latter kind of PPP can turn out to be problematic, and is sometimes quite accurately described as a double-edged sword.

Though many PPPs have the advantage of funding and can also be cost-effective, oftentimes, the private sector and public health sector have different priorities and implementation practices. Private sector involvement in international health may skew the global community’s prioritization of issues and interventions, which may be questionable from a public health perspective. An example would be the prioritization of communicable diseases like HIV/AIDS and malaria in the global health space, which lead to non-communicable diseases and the social determinants of health receiving less resources in spite of their heavy burden.

The importance of trust
The global health architecture is far more complex today than it was only 10-15 years ago. The bureaucratic complexity of the WHO may hamper the will of Member States to involve the Organization in global health projects, and many will instead try to bypass it. For example, it was recently announced that the United States and the African Union (AU) signed a Memorandum of Cooperation to support the establishment of an African Center for Disease Control (CDC) Unit with the help and technical expertise of the United States CDC. The Lancet notes that the press releases about this venture fail to mention any WHO involvement, something that could indicate a lack of confidence in WHO policy-making and implementation capacities.

I believe that public health is all about trust, and the WHO need to regain the trust of the international community. Gostin and Friedman see the tragic Ebola epidemic as a window of opportunity to build a robust, universal global health system, once and for all. They propose a new global health framework, with strong national systems at its foundation and an empowered WHO and well-coordinated funding supporting the health of member states. Achieving this system requires a change in the budget allocations concerning voluntary and assessed contributions, and a WHO with more budget control. An empowered WHO ought to have the capacity to be a guardian of global health, but this mission will require sufficient funding.

The bottom line is this. If we want to live in a world capable of dealing with global health emergencies, like SARS and Ebola, we need to pay for it. 2015 is a seminal year for global health, marking 70 years since World War II, and the WHO’s establishment, and new opportunities to achieve health for all under Sustainable Development Goal 3.2 (SDGs). Seven decades have passed, but we must not forgot why the WHO was set up in the first place:

The health of all people is fundamental to the attainment of peace and security and is dependent upon the fullest co-operation of individuals and States.

References

World Health Organization. Media Centre. Sixty-eight World Health Assembly opens in Geneva. [ONLINE] Available http://www.who.int/mediacentre/news/releases/2015/wha-18-may-2015/en/ [Accessed 18 May 2015]

WHO Director-General’s speech at the Sixty-eighth World Health Assembly
18 May 2015 [ONLINE] Available http://www.who.int/dg/speeches/2015/68th-wha/en/
[Accessed 21 May 2015]

Médecins Sans Frontières. Report. Pushed to the limit and beyond. A year into the largest ever Ebola outbreak 2015. Available http://www.msf.org/article/ebola-pushed-limit-and-beyond [Accessed 23 March 2015]

Gostin LO & Friedman EA (2015) A retrospective and prospective analysis of the west African Ebola virus disease epidemic: robust national health systems at the foundation and an empowered WHO at the apex. Lancet 385:1902-1909.

World Health Organization. Sixty-eight World Health Assembly. Provincial agenda item 16.1. A68/25 [ONLINE] Available http://apps.who.int/gb/ebwha/pdf_files/WHA68/A68_25-en.pdf [Accessed 8 May 2015]

The Lancet (2015) The African CDC and WHO AFRO. Lancet 385:1592.

WHO. WHO Constitution. [ONLINE] Available http://whqlibdoc.who.int/hist/official_records/constitution.pdf [Accessed 18 May 2015]

Category: Global Health, Global Health Systems, Health, MSF, The Student Blog | Tagged , , , , , , , , , , | 1 Comment

Reflections on using Deep Brain Stimulation (DBS) to treat neuropsychiatric disorders

Deep brain stimulation (DBS) has been used to treat diverse neuropsychiatric disorders, ranging from Parkinson's Disease to OCD. Image courtesy of Saad Faruque.

Deep brain stimulation (DBS) has been used to treat diverse neuropsychiatric disorders, ranging from Parkinson’s Disease to OCD. Image courtesy of Saad Faruque.

By Daniel Albaugh

One of my most fascinating experiences as a doctoral student of neuroscience began with an early morning trip to the university hospital. Upon arrival, my laboratory colleagues and I met with one of the clinical neurologists, who introduced us to a patient suffering from advanced Parkinson’s Disease. Medications were no longer working effectively, and the patient’s motor symptoms were severe and debilitating. The day that we arrived, the patient was to have electrodes implanted deep into the brain circuitry that was misbehaving in his disease, the first step in a revolutionary therapeutic approach known as deep brain stimulation (DBS).

What is Deep Brain Stimulation?

DBS is an increasingly well-utilized therapeutic tool for many neurological diseases, predominantly movement disorders. With this therapy, high frequency electrical stimulation is chronically delivered to a target brain region, powered by a battery source implanted near the patient’s clavicle. In Parkinson’s Disease, the effects of DBS can be dramatic and immediate — resting tremors (shakiness at rest) dissolve, rigid muscles loosen, and many more benefits may be immediately observed.  Although the mechanisms of action are poorly understood, DBS therapy works well when targeted to brain regions in which surgical lesions are also effective. This may suggest that DBS acts to provide a “functional lesion” in brain circuitry, with the added benefits of being reversible and modifiable. If the therapy doesn’t work, or side effects are intolerable, clinicians can try to adjust the stimulation parameters, or as a last step, remove the electrodes.

Not Just for Movement Disorders

An early hint that DBS therapy would be useful in treating other types of brain disorders came in a small case report published in 2002 by Mallett and colleagues, describing two patients that received DBS for Parkinson’s Disease. In addition to their Parkinson’s, these patients suffered from a neuropsychiatric disease termed Obsessive-Compulsive Disorder (OCD). OCD is characterized by recurring, unwanted obsessions and compulsions (e.g., excessive hand-washing, other ritualistic behaviors), symptoms that can be incredibly debilitating and prevent many sufferers from engaging in everyday tasks. Standard treatments for OCD include medication and psychotherapy, which generally work well together to treat disease symptoms. But in a substantial number of cases, these therapies are ineffective.

Mallet’s patients were unable to alleviate their OCD symptoms through medication and psychotherapy, but after using DBS to treat their Parkinson’s Disease, the stimulation came with an unexpected and much-desired side effect — alleviation of their OCD symptoms. According to one patient, the decrease in OCD symptoms was even more satisfying than the alleviation of Parkinson’s symptoms.

Although psychosurgical approaches have a long and contentious history in neuropsychiatry, reports such as this one rekindled enthusiasm for surgical interventions in otherwise treatment-resistant psychiatric patients. Clinical trials for neuropsychiatric DBS therapy have exploded, with a large number of brain targets and diseases under investigation. In 2009, the Food and Drug Administration (FDA) approved the standard clinical use of DBS therapy in treatment-refractory OCD patients, under a Humanitarian Device Exemption Act.

Challenges and Opportunities for Neuropsychiatric DBS Therapy

The challenges associated with DBS therapy are not trivial, particularly for neuropsychiatric diseases. One of the major associated hurdles concerns the identification of optimal therapeutic targets and stimulation parameters (e.g., voltage and frequency). When I shadowed a DBS electrode implantation surgery in a Parkinson’s Disease patient, I noticed that he was kept awake (only lightly sedated) throughout the entire procedure. Although there are no pain receptors in brain, this was surely an uncomfortable experience. However, by being awake, he could provide feedback about how the DBS stimulation tests were working, guiding the final electrode placement deep in the brain. With optimal electrode positioning, the motor symptoms in a Parkinson’s patient may be instantaneously alleviated by DBS. Similarly, stimulation parameters can be readily altered to optimize therapeutic efficacy. This level of clinical feedback cannot be so readily provided in DBS surgery for neuropsychiatric diseases, where symptom alleviation is observed on a timescale of weeks or months, not seconds. Indirect, predictive measures of DBS efficacy have been reported, including smiling and laughter in OCD patients.

The future of neuropsychiatric DBS therapy is bright. At present, most is known about the efficacy of DBS for OCD and treatment-resistant depression, which often target emotional/limbic structures such as the nucleus accumbens. Available data suggests that about half of the patients respond well to this therapy. This is not to say that DBS therapy does not have the potential to work for a greater percentage of patients, or generate larger symptom reductions in responders. New targets and stimulation patterns are actively being tested, and it is exceedingly probable that optimal parameters have not yet been worked out. The ability to implement patient-specific stimulation parameters is a major strength of DBS therapy, and better patient categorization methods (e.g. by subsets of symptoms or biological measurements such as MRI scans), may also help to identify optimal DBS configurations on a more personalized basis.

My visit to the neurology clinic to witness a DBS surgery ended in disappointment. The patient responded suboptimally to the procedure, and the electrodes were not put in place for chronic stimulation on that day. As the neurobiology and clinical insights guiding this therapy become increasingly sophisticated, it is my hope that the number of DBS responders will increase in time. I look forward to the day when no brain disease patient is left without therapeutic options.

References
1. Grill WM, Snyder AN, Miocinovic S (2004): Deep brain stimulation creates an informational lesion of the stimulated nucleus. Neuroreport. 15:1137-1140.
2. Mallet L, Mesnage V, Houeto J-L, Pelissolo A, Yelnik J, Behar C, et al. (2002): Compulsions, Parkinson’s disease, and stimulation. The Lancet. 360:1302-1304.
3. Haq IU, Foote KD, Goodman WG, Wu SS, Sudhyadhom A, Ricciuti N, et al. (2011): Smile and laughter induction and intraoperative predictors of response to deep brain stimulation for obsessive-compulsive disorder. NeuroImage. 54 Suppl 1:S247-255.
4. de Koning PP, Figee M, van den Munckhof P, Schuurman PR, Denys D (2011): Current status of deep brain stimulation for obsessive-compulsive disorder: a clinical review of different targets. Current psychiatry reports. 13:274-282.
5. Bewernick BH, Hurlemann R, Matusch A, Kayser S, Grubert C, Hadrysiewicz B, et al. (2010): Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biological psychiatry. 67:110-116.

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Support Open Access publishing with the click of a button

Support open access publishing by voting for the Open Access Button in the JISC funding competition.

Support open access publishing by voting for the Open Access Button in the JISC funding competition.

The Open Access Button is a web and mobile app that helps students, researchers, patients and the public get access to academic research.

In 2013 two undergraduate students in the United Kingdom, and a team of volunteer developers first led the development Open Access Button project. Now, we’ve grown to a team of over a dozen international students who are committed to helping people gain access to research and advocate for open access, which is the free access and re-use of scholarly research.

People use research articles to learn about the world around them and advance scientific understanding. However, most people are unable to access research because individual articles can cost more than $40. Cost barriers have lead to very real deficits in scientific knowledge, sometimes with extreme consequences. In fact, a New York Times article written by a team leading Liberia’s Ebola recovery plan underscores the importance of open access publishing. The team found a paper published in 1982 that first warned Liberia was at risk for an Ebola epidemic, but because the findings were locked behind a pay wall, national researchers were likely unable to access this potentially life-saving information. Open access can solve problems like making life-saving information publicly available, to helping a student get research for their term paper. The Open Access Button provides users with a quicker connection to open research than if they searched independently.

In November 2013 we launched our Beta and recorded more than 12,000 instances of people without access to research articles. Next, we expanded the Open Access Button by launching a new website, adding new features such as the wish list to provide users with the research they need, and developing a mobile app through funding from the JISC Summer of Student Innovation in 2014. An international team of students running off volunteer time and small grants led the mobile app development. Now we’re seeking to increase the benefits of the Open Access Button by adding a frequently requested feature to automatically email an author when a copy of the research isn’t publicly available. But to achieve this, we need your help.

We’re up for £20,000 (US $31,000) in funding from the JISC Supporting Startup Projects. This funding would be allocated to developing the feature allowing users to generate automatic emails asking an author to make their paper available through an Open Access repository.

Emailing authors directly has long been used as a tactic to request copies of papers behind pay walls. This new feature will allow users to engage with authors in a familiar way, increase compliance while not duplicating university services, and provide simple advice to authors on how to archive their research in existing repositories. If the article was then archived in a repository then the user who requested the paper would be informed. Also, this feature allows us to promote historical archiving of previously published research, which extends past policy changes that only affect newly published articles.

JISC funding will primarily provide development and testing of the new feature, as well as travel and promotional expenses to ensure consultation, feedback and promotion. Additional support during the startup period will assist long term planning to embed within universities and become sustainable. We also hope to attract more users to the Open Access Button with this new feature. The qualitative and quantitative data generated can support efforts by open access advocates to improve the scholarly publishing system in the future.

We call on PLOS readers and researchers to help us expand our open access advocacy and promote access to all research both historical and recent. Visit our JISC Supporting Startup Projects page to support the Open Access Button. Voting ends on Monday, 25 May.

To get your own Open Access Button for free or to find out more please visit www.openaccessbutton.org. Tweet @OA_Button or email hello@openaccessbutton.org if you have any questions or would like to collaborate.

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Battling misinformation: The scientific consensus as a gateway belief for climate change and GMOs

Greenland's glaciers have been breaking off into the Atlantic Ocean at an accelerated pace due to the effects of climate change. Photo courtesy of Tim Norris.

Greenland’s glaciers have been breaking off into the Atlantic Ocean at an accelerated pace due to the effects of climate change. Photo courtesy of Tim Norris.

By Joseph Timpona
Public debate on scientific topics is in no short supply. Though science recognizes the evidence validating evolution, genetically modified organisms (GMOs), or climate change, it does not take long to find articles or people who oppose regarded scientific facts. In many of these cases, unnecessary debate inhibits positive action. Also, confronting these debates effectively is no trivial task. Studies have shown that administering facts to people may only harden their misguided beliefs. Therefore, finding effective ways to inform the public about issues pertaining to science and society is imperative to driving support for evidence-based policies. A recent PLOS ONE article provided causal evidence that people’s initial assumptions about the scientific consensus on climate change — known as a “gateway belief” — may help shape people’s perceptions of climate change and make them more likely to support action.

A major motivator of climate change doubt is public misunderstanding about the scientific consensus on the issue. Agents of doubt have successfully promoted the false message that it is up for debate among scientists whether human action is causing climate change. This sentiment is untrue. Nine out of every 10 scientists believe that human activities are the primary driver of global climate change. However, only one in 10 Americans correctly estimates that the consensus is this high. Moreover, science demonstrates that knowledge of this consensus can influence whether people acknowledge the fact of climate change.

Testing the Gateway Belief Model

Van der Linden and colleagues hypothesized that study participants would be more convinced of the evidence behind global warming if they knew about the high scientific consensus. Thus, knowledge of the scientific consensus would serve as a gateway belief to facilitate other key beliefs about climate change and support for action. The novelty of their approach was that it would provide causal instead of correlative data — something that has remained elusive in these types of studies.

Through mathematical modeling, the scientists found a direct causal relationship between knowledge of the scientific consensus and support for public action. Also, people who learned of the scientific consensus were more likely to worry about climate change, and believe that the phenomena is happening and caused by humans.

However, following the study, the increase in support for action was not nearly as substantial as the increase in the participant’s ability to correctly estimate the scientific consensus. While understanding of the scientific consensus makes some people more likely to support public action, the gateway belief model will not influence everyone. There are likely other factors involved in making someone support action.

Using the Scientific Consensus to Combat Public Misunderstanding

These results provide promise. The findings indicate that the gateway belief model can be used to inform the public and increase the likelihood that support will be generated for action to be taken. Even if the gateway belief model influences only a fraction of the population to support action, even small shifts in public support for an issue can have expansive consequences. The results beg the question, “Can the gateway belief model be extended to other science issues?”

I would argue that climate change is the most pressing issue in science, with huge impacts for society if it is not addressed in a timely manner. But public discourse on other scientific issues is fraught with similar misunderstandings. For example, data from a Pew research poll that compared differences in opinion between the public and scientists indicated that the biggest gap between the two groups was on the issue of GMOs in food. 88% of AAAS scientists think that it is safe to eat genetically modified foods, while only 37% of adults in the United States believe that it is safe — a gap of 51%. For comparison, the public/scientist gap on climate change being mostly due to human activity was 37%.

Using the scientific consensus as a gateway belief to build support for GMOs in food has not been addressed yet, but it would be interesting to examine for two key reasons. First, it is harder to promote discourse on issues such as GMOs in food because they appeal to people’s core values on different levels. Most of the debate around GMOs is not actually debate about the science, but rather is a debate of values. Second, if the gateway belief model were successful in educating, then it would embolden the idea that it is an effective strategy to combat misinformation and could be extended to other issues such as vaccine denial. If it were not effective at garnering change in GMO understanding, then it would indicate differences between these issues that go beyond the misunderstanding of the scientific consensus.

Curbing Doubt with Science

When trying to communicate topics such as climate change to the public, scientists should consider employing the gateway belief model to best understand how to drive change and engender support. Assaulting people with facts is becoming an antiquated technique in science communication. While informing people of the scientific consensus is technically providing a fact, the existence of a consensus is something that cannot really be disputed, and is far enough removed from the core values of individuals. The use of the gateway belief model then allows people to acknowledge these facts on their own, which is important for maintaining them.

References

The New Yorker. 2014. “I Don’t Want To Be Right”. [ONLINE] Available at: http://www.newyorker.com/science/maria-konnikova/i-dont-want-to-be-right. [Accessed 9 May 15].

van der Linden SL, Leiserowitz AA, Feinberg GD, Maibach EW (2015) The Scientific Consensus on Climate Change as a Gateway Belief: Experimental Evidence. PLoS ONE 10(2): e0118489. doi:10.1371/journal.pone.0118489

Pew Research Center. 2015. Public and Scientists’ Views on Science and Society. [ONLINE] Available at: http://www.pewinternet.org/2015/01/29/public-and-scientists-views-on-science-and-society/. [Accessed 10 May 15].

Leiserowitz A, Maibach E, Roser-Renouf C, Feinberg G, Rosenthal S (2014) Climate Change in the American Mind: American’s Global Warming Beliefs and Attitudes in April 2014. Yale University and George Mason University. New Haven, CT: Yale Project on Climate Change Communication. http://environment.yale.edu/climate-comm​unication/files/Climate-Change-American-​Mind-April-2014.pdf

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Re-launching the PLOS Student Blog & Introducing Travel Awards!

Hi PLOS readers!
My name is Sara Kassabian, and I am a Masters candidate in the Global Health Sciences program at University of California San Francisco. I recently joined the PLOS community as Social Media Coordinator, and I’m pleased to announce some exciting new developments from PLOS impacting student scientists and early career researchers:

•       In collaboration with some talented student bloggers, PLOS is re-launching the PLOS Student Blog. If you’d like to contribute, there are still opportunities for science writers who are still in school or at the early stages of their careers to join this team blog.

•       May 1 opens the applications for the PLOS Early Career Research Travel Awards, a program that awards $500 to 10 PLOS authors who are early in their careers to disseminate their research findings at scientific conferences.

The PLOS Student Blog

Since the inception of PLOS BLOGS Network in 2010, the PLOS Student Blog has served as a forum for accomplished science students and skilled science writers to share their thoughts on scientific education, and to discuss their own research. At PLOS, we encourage the next generation of scientists to couple creative ingenuity with rigorous inquiry in their research.

The Student Blog is a platform to foster these skills, and it provides a forum to connect students with their colleagues and other accomplished PLOS authors. Some of our most popular student posts from the past included “Why Science Journal Paywalls Have to Go”, “Ebola Immunopathology and the Outbreak in West Africa”, and “Happy New Year from the Student Blog”, for an excellent round-up of past posts.

Contributing to the PLOS Student Blog

If you are interested in contributing to the PLOS Student Blog, please email Sara at skassabian@plos.org with a brief email introducing yourself, your institution, your concentration, and writing samples (if you have them). We are looking for diverse representation of scientific disciplines, institutions, and levels of education.

Past contributors have included post-docs, medical students, and other graduate students, however exceptional undergraduate students are also encouraged to apply. Past writing experience is encouraged, but not required. Student bloggers can write a single post on a burning interest, or become regular contributors with periodic posts over the coming semester or year. All contributors are required to abide by the PLOS Community Guidelines. Please note that all PLOS content is open access under Creative Commons License Four.

Apply for the PLOS Early Career Travel Award Program here: https://www.plos.org/travelawards/

Apply for the PLOS Early Career Travel Award Program here: https://www.plos.org/travelawards/

PLOS Early Career Travel Award Program

At PLOS, we understand that some of our authors that are in the early stages of their career need extra support to disseminate their research findings widely. The PLOS Early Career Travel Award Program is an opportunity for us to cover up to $500 in expenses for up to 10 selected participants. Applications opened on May 1, and PLOS is accepting applications until June 30 at 12pm PDT.

Am I eligible for the program?
To be eligible, applicants must meet all of the following criteria:
1. Be a presenting author on a paper or poster at the scientific conference indicated on the application form; the conference must take place between August 1, 2015 and December 31, 2015.
2. Be an author on an article published in any PLOS journal by the application date; deadline for applications is June 30, 2015.
3. Be part of a graduate program or have received a graduate degree within the last five years as of the June 30, 2015 application deadline.

For any questions remaining questions about the Early Career Travel Award program, visit us online here, or email us at travelawards@plos.org.

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Neglected Tropical Diseases: Challenges for the Post-2015 Development Era

This article is being cross-listed with the Harvard graduate student publication Signal to Noise, Special Edition on Infectious Disease.

Health equity is based on the idea that all lives, anywhere in the world, have equal value.

Neglected Tropical Diseases (NTDs) are a group of 18 infectious diseases – caused by parasites, viruses, or bacteria – that disproportionately affect the poor and cause significant health and financial burdens. NTDs are endemic – meaning that they regularly infect humans – in 149 countries, with over 1 billion people infected and 2 billion people at risk. These diseases are largely treatable and preventable through control of the insects that carry these diseases, improved water quality and sanitation, and the efficient delivery of drug treatments already donated by major pharmaceutical companies. The control and elimination of NTDs cuts across the United Nations’ eight Millennium Development Goals for 2015. Controlling NTDs would not only reduce disease burden but would also improve maternal health, reduce childhood mortality, reduce malnutrition, improve school attendance, and help to empower women. With just a year left on the Millennium Development Goals clock and these diseases still constituting a major burden, we are at a pivotal time for infectious diseases and global health. By defining a clear way forward in the post-2015 development era, we stand to make major progress toward the control, elimination, and eradication of NTDs and other diseases.

What are Neglected Tropical Diseases?

The World Health Organization (WHO) prioritizes 17 neglected tropical diseases (NTDs) (Figure 1) that affect over a billion of the world’s poorest people and pose a significant economic burden to developing economies (scabies was just added to the list in June of 2014, bringing the count to 18). NTDs are a heterogeneous group of infections caused by parasites, viruses, and bacteria. What makes NTDs different from non-neglected diseases is that these diseases are disablers rather than killers. Indeed, these infections are co-endemic: an individual may be infected with more than one NTD in addition to other well-known diseases such as HIV, tuberculosis, and malaria. For example, the parasite infection schistosomiasis can make women and girls more susceptible to HIV infection, saps micronutrients and iron from developing children to stunt their growth, and renders children less likely to attend school. A chronic helminth parasite infection known as lymphatic filariasis (LF) may reduce vaccine efficacy by broadly modulating the immune system. LF causes severe swelling (lymphedema) in 40 million people rendering them socially stigmatized and largely unable to work. In addition to schistosomiasis and LF, many more NTDs are characterized by chronic disabilities, increased susceptibility to infectious and non-infectious diseases, social stigma, and an economic burden on the individual, the family, and the country.

Figure 1

NTDs don’t just affect low- and middle-income countries, although their victims are often socioeconomically disadvantaged. Cysticercosis, echinococcus, toxocariasis, Dengue virus, West Nile virus, and Chagas disease all have appeared in the United States, disproportionately afflicting the poor. Peter Hotez of the Sabin Vaccine Institute and Baylor College of Medicine has estimated that half of the 20 million people living in poverty in the US are infected with at least one NTD.

How NTDs cut across the Millennium Development Goals

The Millennium Development Goals (MDGs), established following the Millennium Summit of the United Nations in 2000, are a list of 8 objectives aimed at lifting the world’s poorest countries out of poverty by 2015. MDG 6: Combat HIV/AIDS, malaria, and other diseases, most directly applies to NTDs, which fall into the “other diseases” category. The idea that NTDs fall under the “other diseases” umbrella is also now an old one, as NTDs have rightly gained much more attention over the past 10 years as a significant development burden.

The Global Network for Neglected Tropical Diseases issued a report outlining the contribution of NTDs to hindering progress on several other MDGs. With respect to MDG 4: Reduce Childhood Mortality, for example, a child infected with any of the helminth parasites will be anemic and malnourished with a compromised immune system, making it much more likely that that child will succumb to another infection. Children harboring one or more NTDs are also less likely to have regular attendance in school, contributing to MDG 2: Achieve Universal Primary Education. In fact, a study of schools in Western Kenya demonstrated that treating intestinal parasite infections by mass drug administration programs can improve school attendance by up to 25%.

One metric that captures the impact of diseases that disable rather than kill, like many of the NTDs, is the Disability Adjusted Life Years (DALYs) calculation. One DALY can be thought of as one lost year of healthy life to an individual, either by mortality or by disability. Estimates place the burden of Disability Adjusted Life Years (DALYs) lost to NTDs at 26.6 million in 2010, but this is likely a gross underestimate if we consider the secondary effects of NTDs. For example, NTDs contribute to an estimated 15-30% of lost productivity in endemic countries. The coordinated effort to control, eliminate, and eradicate NTDs is not only an issue of human health, but one of economic development.

Recent Progress: NTDs are a Big Bang for the Development Buck

In addition to improving human health and health equity, combating NTDs is a strong and cost-effective method of increasing economic growth. For example, the early results of the Global Programme to Eliminate Lymphatic Filariasis has generated a return on investment of $20-$60 for every US$1. Recognizing this opportunity, the US Congress committed funding support through USAID for the integrated control of NTDs in 2006, and in 2008 the UK Department for International Development also committed funding for NTD eradication. The Bill and Melinda Gates Foundation and the World Bank have also committed significant aid to fighting NTDs over the past decade, followed more recently by other international aid funds.

The First WHO Report on Neglected Tropical Diseases published in 2010 brought NTDs to the forefront. The WHO released a follow-up report in 2012, closely followed by the 2012 London Declaration to control, eradicate, or eliminate by 2020 ten NTDs (lymphatic filariasis, trachoma, soil-transmitted helminths, onchocerciasis, schistosomiasis, leprosy, guinea worm, visceral leishmaniasis, Chagas disease, and human African trypanosomiasis). The London Declaration has been notably effective in kick-starting a strategic and directed effort in the battle against NTDs. It brought together global health leaders including the Gates Foundation and the CEOs of ten pharmaceutical companies to guarantee the donation of an unlimited amount of medicines for these 10 NTDs for the foreseeable future.  The NTDs agenda has been characterized by these strong public-private partnerships, which will be key for continuing progress.

Uniting to Combat NTDs, the coalition of partners and individuals formed during the London Declaration, issued their second progress report in 2014. The report highlights a large upwelling in political will in countries where one or more NTDs are endemic. For instance, demand for drugs for NTDs has increased by 35% and has been matched by industry donations, and there has been an increase in mass drug administration programs. Funding for NTDs has also increased, led by USAID, the UK Department for International Development (DFID), the World Bank, and the Bill and Melinda Gates Foundation. New rapid diagnostic tests for Human African Trypanosomiasis will streamline diagnosis and treatment, and there is now a new pediatric formulation of praziquantel to treat childhood schistosomiasis.

We have effective drugs for most NTDs. The major challenge, and the cost, is effectively and efficiently delivering those drugs to endemic regions. We are now in the position to ask, “What kind of mass drug administration (MDA) regime might lead to local eradication? And can we coordinate the delivery of multiple drugs for multiple diseases at the same time? With the end of 2015 only a year away, we must also ask, “What’s next?”

Looking Ahead: Innovation for NTD Elimination and Control

Since the London Declaration, some successes indicate that control and eradication are possible. Colombia recently became the first country in the world to eradicate onchocerciasis. Niger, Nigeria, and the Ivory Coast have also recently eradicated Guinea worm. Twenty-three countries treated at least 75% of children at risk for soil-transmitted helminth infections,  and a massive disease mapping program of blinding trachoma using mobile technology has cut the unmapped regions of the world for this disease in half.

However, we still have a long way to go. It has been estimated that of all the drugs approved for distribution, only 65-75% are reaching the people who need them. Implementation and operational research on how to carry out mass drug administrations effectively must be a priority. Even when control programs go well, they can be quickly derailed by political unrest, natural disasters like Superstorm Haiyan, or even epidemics like the ongoing Ebola outbreak that have overwhelmed the existing health systems in Liberia and Sierra Leone. Furthermore, disease boundaries for mosquito-transmitted diseases are especially sensitive to changing temperature and precipitation patterns due to climate change.

Last November in his keynote address to the American Society of Tropical Medicine and Hygiene, Bill Gates highlighted a need for global health innovations, citing the example of the new diagnostic test for human African trypanosomiasis. Gates urged the community to take the digital revolution and apply it to disease surveillance to determine where to concentrate disease-fighting efforts The Bill and Melinda Gates Foundation is a strong proponent that “big data” health care informatics solutions must be apart of efficient disease control programs, and this will represent a burgeoning area of global health research in the near future.

As the clock on the 2015 Millennium Development Goals runs out, planning for the post-2015 Sustainable Development Goals. is well underway. What do you think are the biggest issues facing human development today and in the near future?  You can take a look for yourself to see if NTDs will make the cut by reviewing the proposals for the Sustainable Development Goals using the Overseas Development Institute’s http://tracker.post2015.org.

Rachel Cotton is a PhD student in the Harvard Immunology Program, with an interest in infectious disease, global health, and science policy. Her past research has included the immunobiology of parasitic diseases. Follow her on Twitter @RachCotton.

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ISCB Student Council – Documenting the efforts of student organisation volunteers

A guest post by: Geoff Macintyre, Thomas Abeel, Magali Michaut

In July 2014 the International Society for Computational Biology Student Council will celebrate it’s 10th anniversary. Over its ten years of operation, the Student Council has grown to over 2000 members thanks, in a large part, to its constituent of innovative and enthusiastic volunteers. These volunteers have worked hard to uphold the Student Council’s mission of “promoting the development of the next generation of computational biologists”. While many of the volunteers have not received any direct recognition for their contributions, each and every one of the Student Council members will attest that the reward lies in the skills and experience gained in being part of organising an event or activity.

 

However, to ensure that both the efforts of these student volunteers did not go unnoticed, and that their collective experiences could be shared with others, the Student Council put together a series of article documenting various aspects of the Student Council initiatives that PLOS Computational Biology is publishing in conjunction with ISCB. Many of the articles are now published and have been launched as a PLOS Collection.

 

The first article is a great source of information regarding the series and the Student Council. But as a supplement to the series, we thought we would use this post to demonstrate the benefits of being involved in the Student Council by explaining the story behind the creation of the article series. For us personally it was a tremendously rewarding experience and taught us as much about collaborative writing as it did about differences in education backgrounds and culture of our co-authors.

 

The story

While the Student Council has had the opportunity to share proceedings from the annual Student Council Symposium in the past (1-7), there were only a handful of examples of Student Council initiatives being shared with the broader community (8). To rectify this, in early 2012 Nelson Ndegwa and Magali Michaut, both active members of the Student Council, put a call out to all members to see if they would like to share their experiences organising and running events in a paper. The response was overwhelming with many of the leaders from the Regional Student Group program sharing their successes (and failures) in organising initiatives for students from their home country. Originally the collaborative writing environment of WikiGenes was used but, after the expansion to a second page and over 20 authors, this quickly became unwieldy. The other problem was that, with so many stories demonstrating different experiences, different themes, and different writing styles, it was becoming near impossible to condense it all down into one body of writing representing the essence of the Student Council volunteer experience. At the time, Geoff was Chair of the Student Council and had contributed some stories from his time in the Australian Regional Student Group. Seeing the potential arising from this writing effort he took the project to his colleagues in the Student Council executive team and they agreed to set up a small team to oversee and coordinate the writing efforts which included Magali Michaut, Thomas Abeel and Geoff Macintyre.

 

Initially, we attempted to extract some of the abstract concepts from the stories to see if we could write an overarching piece. However, we realised that a lot of the personal nature and details of the experiences were lost. The only way to capture details and write a relatable story was to split up the monolith into many small focused stories. At ISMB 2012 we approached PLOS Computational Biology and the ISCB Publications Committee with a plan to write 12 short articles to document the efforts of Student Council members in various endeavors and hopefully entice others to get involved. After some discussions, and early support from committee members Scott Markel and Olga Troyanskaya, it was agreed that the ISCB pages as part of PLOS Computational Biology would be a good fit for the article series. Needless to say we were rather excited by this news, but then we faced the challenge to coordinate the writing of these articles!

 

Much time was spent on Skype to develop a strategy to deliver twelve high quality articles in a timely manner. We wanted to give every member an opportunity to contribute to the series, but we wanted to ensure no-one was simply along for the ride. We therefore decided to have one person as a lead author on each article (selected from those who initially contributed to the stories) and one of us to oversee each article. Each lead author had to select passages of text from the original stories collected on WikiGenes which were relevant to their article and invite the author of that text to be part of their article. An additional announcement was put out with the description of each article and any students who wished to be involved had to submit to the lead author a short piece of writing relevant to the article. This process resulted in an average of four potential authors per article – we made it clear that authorship would be determined based on contributions after the article was written.

 

We opted to use Google Docs for the writing of each article as it allowed simultaneous editing of the articles and the ability to track the edits. Initially, the authors were required to provide an outline of the article which had to be discussed amongst all authors via Skype. Once this was done, we provided additional feedback and writing could commence. Naturally each article went through a number of drafts with all authors working on different aspects of each article. Once the final drafts of the articles started to trickle in, they were sent out to previous Student Council members who volunteered their time providing ‘peer review’ feedback on each article. Their comments were taken into account and each article was revised accordingly. With the articles in a final draft form, we discussed with the lead authors the contributions of everyone involved and authorship was jointly decided – a process that went surprisingly smoothly.

 

At this stage, the articles were ‘nearly’ ready for submission. The only problem remaining was that the articles lacked flow or clarity in parts. This was likely a byproduct of having authors from different countries writing in conflicting styles and for quite a few of the authors it was the first journal paper they ever wrote. To overcome this, and drawing on the inspiration of the astounding volunteer efforts of the Student Council members, we sought out students from another discipline – in this case professional editing students – to see if they would volunteer their time in editing the article to improve readability. To our delight, Stephanie Holt, from RMIT University agreed to put forward our articles to her Advanced Manuscript Editing students, as a group exercise in practicing their editing skills. As such, we received a collection of suggested changes which dramatically improved some of the articles.  The articles were finally ready for submission.

 

Since then, we have submitted each article sequentially, which are now being published with the help of the teams at PLOS (currently up to article 10 of 12). Overall the experience was immensely rewarding. The process of having to coordinate the collaborative writing efforts honed our planning and time management skills, made us realise the benefit (and limitations) of using collaborative writing software, and helped us get more familiar with the process of taking an idea through to publication. However, most interesting for us, was the insight into cultural and educational differences between our co-authors from around the globe, including Africa, Europe, South and North America. For example, different authors had different ideas about how and what they could talk about when critically analysing their own education experiences. No-doubt these insights will help us in future collaborations during our scientific careers.

 

Looking back on some of the articles that have been published, we hope that many of the Student Council members feel proud that their volunteer efforts have been shared with the broader community. But more importantly, it will be exciting to see if the articles in this series can inspire other students to see the benefits in volunteering in student organisations and contributing to their scientific community.

 

 

1. Gehlenborg N, Corpas M, Janga S (2007) Highlights from the Third International Society for Computational Biology Student Council Symposium at the Fifteenth Annual International Conference on Intelligent Systems for Molecular Biology. BMC Bioinformatics 8: I1. doi: 10.1186/1471-2105-8-s8-i1

 

2. Peixoto L, Gehlenborg N, Janga S (2008) Abstracts of the Fourth International Society for Computational Biology (ISCB) Student Council Symposium. Toronto, Canada. July 18, 2008. BMC Bioinformatics 9 Suppl 10: I1–P6. doi: 10.1186/1471-2105-9-s10-i1

 

3. Abeel T, de Ridder J, Peixoto L (2009) Highlights from the 5th International Society for Computational Biology Student Council Symposium at the 17th Annual International Conference on Intelligent Systems for Molecular Biology and the 8th European Conference on Computational Biology. BMC Bioinformatics 10 Suppl 1: I1 doi: 10.1186/1471-2105-10-S13-I1.

 

4. Klijn C, Michaut M, Abeel T (2010) Highlights from the 6th International Society for Computational Biology Student Council Symposium at the 18th Annual International Conference on Intelligent Systems for Molecular Biology. BMC Bioinformatics 11: I1. doi: 10.1186/1471-2105-11-s10-i1

 

5. Grynberg P, Abeel T, Lopes P, Macintyre G, Pantano Rubiño L (2011) Highlights from the Student Council Symposium 2011 at the International Conference on Intelligent Systems for Molecular Biology and European Conference on Computational Biology. BMC Bioinformatics 12: A1. doi: 10.1186/1471-2105-12-s11-a1

 

6. Goncearenco A, Grynberg P, Botvinnik O, Macintyre G, Abeel T (2012) Highlights from the Eighth International Society for Computational Biology (ISCB) Student Council Symposium 2012. BMC Bioinformatics 13: A1. doi: 10.1186/1471-2105-12-s11-a1

 

7. Di Domenico T, Prudence C, Vicedo E, Guney E, Jigisha A, Shanmugam A (2014) Highlights from the ISCB Student Council Symposium 2013. BMC Bioinformatics 15(Suppl 3):A1  doi:10.1186/1471-2105-15-S3-A1

 

8.  Gichora NN, Fatumo SA, Ngara MV, Chelbat N, Ramdayal K, et al. (2010) Ten Simple Rules for Organizing a Virtual Conference—Anywhere. PLoS Comput Biol 6(2): e1000650. doi: 10.1371/journal.pcbi.1000650

 

 

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Mechanization, Automation, and the Future of Biological Research

Much like a bicycle leverages mechanical advantage to propel a person much faster and further than on his or her own, automation machinery is amplifying both the speed and accuracy with which biological research can be conducted. Machines are precise and do not fatigue, unlike their human counterparts. For this reason, machines are slowly being adopted for laborious, repetitive, and tedious laboratory tasks.

Some automation machines, like the flow cytometer seen here, have already become widely used pieces of laboratory equipment.

There are two ways of thinking about machines in the modern scientific community: physical, mechanical machines and laboratories, institutes, and facilities to which experiments can be outsourced. The former of these are often tailored to a single specific task. Tasks can include phenotypic screening, liquid transfer, and even laboratory organism maintenance. Mechanical machines are perfect for performing repetitive, tedious lab work inside the laboratory. Many of these machines offer sensors that can detect and measure traits that would be otherwise immeasurable by hand. When utilized properly, mechanical machines can greatly increase precision, efficiency, and reproducibility while reducing overall workload. Mechanical machines, while massively advantageous when working properly, often lack the ability to sense their surroundings or steps in their mechanical processes. Therefore, it is nearly impossible for these machines to adapt to conditional changes or for certain segments of the machine to provide feedback to other segments, either to adjust processes or alert their human keepers to an issue.

Great strides must be made in the design and engineering of experimental machinery so as to reduce innate variability of experimental setup and screening. Human’s, sentient beings, can sense and adjust to errors made mid-experiment. If too much of a solution is added to a reaction, a person can adjust the rest of the protocol on the fly or, at worst, begin the reaction over again. If the same error is made by a machine, it may go unnoticed until the output data are collected. Even worse, it may go completely unnoticed, presenting false data that are interpreted as correct upon analysis. Likewise, if the error is due to the improper functioning of a device, such as a pipette in the above example, a human is more likely to notice the error in the first place as we are equipped with sensors, i.e. eyes, that can detect that the volume transferred does not match the volume desired. Such sensors and feedback networks are currently not available on many of the mechanical machines being utilized in experiments.

The second way to think about machine automation in science is through the outsourcing of experiments to external research labs, institutions, or facilities. These organizations will take, as input, reagents or experimental parameters and return the output reagents or data back to the experimenter. These organizations can be thought of as automation machines because they take input and serve output from and to experimenters without any further involvement or work from the experimenter. The most common example of this process is that of DNA sequencing. While DNA sequencing has become a routine task in many modern laboratories, only a small minority of labs own and operate their own sequencing machine, either due to financial cost or lacking an operator with the requisite expertise and experience. Instead, most laboratories outsource this process to external organizations that specialize in DNA sequencing.

Perhaps the greatest advantage of the utilization of automation machinery is the ability

In the future , labs may use mechanical arms to transfer experiments between machines like incubators and flow cytometers. Labs may more closely resemble car assembly lines than the labs of today.

to pipeline experimental segments into one another. For example, laboratories can now outsource the creation of a specific reagent, the utilization of the reagent in a specific experiment, and the measurement of the outcome of the experiment all without conducting any work in their own laboratory. While the jury is still out on whether this pipelining technique will ever lead to any “virtual laboratories” where investigators simply dream up experiments, outsource their execution, then analyze the data, it is important to note that the modularization of experiments will almost certainly lead to increased efficiency in much of modern science. Instead of spending money on training and technicians to run repetitive short-term experiments, researchers now have the capacity to outsource these experiments to either mechanical machinery in their own lab or external research organizations for a fixed, per-experiment cost.

Automation can increase the productivity of a single individual by orders of magnitude. Machines do not tire or vary innately in their performance of a task; however, machines can break, suffer inaccuracy or variability in their measurements, and not detect faults when they may be blindingly apparent to a human. For these reasons, great care must be taken in protocol derivation and maintenance scheduling when utilizing any form of automation equipment.

When utilizing machinery in the design and/or execution of an experiment, the most important variable to consider is the trustworthiness of the data at each individual step. If unnoticed, systematic biases in data collection resulting from measurement error of machinery can lead researchers astray. Additionally, variability between experimental runs must be considered. One sign of data trustworthiness is reproducibility of the data. If the same experiment is replicated under the same conditions, the data resulting from each round of the experiment should be, at best, identical or, at worst, comparable. Although automation machinery has the incredible upside potential to streamline and parallelize experimental workflows, scientists must be careful to thoroughly validate results, both data and reagents.

 TylerShimko_HeadshotTyler Shimko is an undergraduate studying and conducting research in biology at the University of Utah. You can follow him on Twitter @TylerShimko

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Ebola Immunopathology and the Outbreak in West Africa

Ebola virus (EBOV) is a highly virulent pathogen, resulting in death by Ebola hemorrhagic fever in up to 90% of people who contract the virus. There are no drugs to treat it, and no vaccines yet to prevent it.

There is an Ebola outbreak in West Africa, and it has been ongoing for several months, since the first death occurred in December 2013. The most recent counts from the World Health Organization include 328 cases, with 208 deaths, in Guinea so far, with additional cases in Liberia and Sierra Leone. Between May 29 and June 1 alone, there were 37 new reported cases and 21 deaths.

Cases of Ebola are occurring throughout Guinea, Sierra Leone, and Liberia. Credit: E.Ervin/CDC

Cases of Ebola are occurring throughout Guinea, Sierra Leone, and Liberia. Credit: E.Ervin/CDC

By April, Médicins Sans Frontières  (Doctors Without Borders), which has been the lead aid organization for the outbreak, was calling the epidemic  ‘Unprecedented’. What makes this epidemic different, in addition to the fact that this is the first outbreak of Ebola in West Africa, is that cases are not geographically isolated. Cases have been occurring throughout Guinea, and now Sierra Leone and Liberia as well. Senegal even closed its borders to Guinea in April for fear of spread of the virus.

Ebola virus is carried by fruit bats, and is transmitted to and among humans and other primates by blood and bodily fluids at skin and mucosal surfaces. The most common routes of exposure for humans are handling infected bushmeat, contact with the remains of an individual who has succumbed to the virus, or occupational exposure to health workers by needle-stick.

The strain causing the present epidemic has been sequenced and characterized, and was published in the New England Journal of Medicine in April. It represents the emergence of a new clade of the virus – unique, but related to Zaire ebolavirus, an extremely virulent strain that has caused epidemics in the Democratic Republic of the Congo and Gabon.

So what makes Ebola virus so deadly? And why do some individuals progress to Ebola hemorrhagic fever and death, whereas others recover?

Ebola Immunopathology

Ebola immunopathology is characterized by uncontrolled inflammatory responses by monocytes and macrophages in the early stage of infection, coupled with immune suppression and the destruction of several cell types including dendritic cells (DCs) and endothelial cells in the later stages of infection. This ultimately leads to the collapse of the vascular system, shock-like symptoms, uncontrollable hemorrhaging, and death.

Compared to those who recover from Ebola infection, victims exhibit high viral loads, an absence of cytotoxic CD8 T cell activation, below-normal numbers of T cells, and high nitric oxide production, a sign of macrophage activation. Furthermore, recovered individuals have detectable levels of anti-EBOV antibodies in the blood at the onset of symptoms, whereas susceptible individuals do not. Those who succumb to the virus mount a robust but ineffective innate inflammatory response, followed by a failure to induce adaptive immunity. Viral replication and cell death continue, unchecked.

How is it that the innate response is both strong and ineffective?  This paradox can be explained by differential effects of ebola virus on macrophages and DCs. While strongly activating monocytes and macrophages, ebola-infected DCs are inhibited in activation and function.

Ebola activates monocytes and macrophages

Virus-activated monocytes and macrophages secrete an abundance of proinflammatory cytokines and chemokines like tumor necrosis factor (TNFa), IL-1β, macrophage inflammatory protein-1a, and reactive oxygen and nitrogen species, and large numbers of infected macrophages undergo activation and apoptosis. However, this is insufficient to deter viral spread. Macrophage apoptosis recruits more monocytes and neutrophils that further the inflammatory response and provide new host cells for the virus.

The unchecked production of pro-inflammatory mediators is cytotoxic to the surrounding tissue, and likely contributes to the hemorrhagic pathology of Ebola infection, by increasing vascular permeability. That is not to down-play the effects of the virus itself, which has a particular tropism for innate immune cells and endothelial cells, and induces cell lysis in most if not all cells it infects.

Ebola virus virion.  Colorized transmission electron micrograph (TEM) Credit: Cynthia Goldsmith/CDC

Ebola virus virion. Colorized transmission electron micrograph (TEM) Credit: Cynthia Goldsmith/CDC

Ebola impairs and co-opts dendritic cell function

Dendritic cells (DCs) serve as the bridge between innate and adaptive immunity. When functioning normally against infection, DCs internalize a pathogen or a piece of it, and then process and present signatures of that pathogen to T cells in the lymph node. Dendritic cells also secrete activating cytokines like interferons (IFNs) and IL-12, and express co-stimulatory molecules to further induce responses from cells of the adaptive arm. Ebola virus, however, inhibits dendritic cell function by several mechanisms. Ebola-infected DCs fail to secrete IFNs and other pro-inflammatory cytokines, fail to upregulate  costimulatory molecules, are impaired in antigen presentation and processing, demonstrate increased expression of inhibitory molecules, and are in all poor activators of T cells. These effects are dependent on the Ebola envelope glycoprotein.

A particularly interesting feature of Ebola, is that its sticky! The virus binds C type lectins on the surface of a number of cell types, including the lectin DC-SIGN which is highly expressed on dendritic cells. The benefit of this for viral pathogenesis is unclear, but may facilitate viral entry into DCs and other cells, or may simply allow the virus to hitch a ride through the lymphatic system and disseminate infection.

Outlook

The immune response to Ebola virus gets only half-way there in fatal cases. The innate immune system is alerted and activated, but then the virus inhibits the initiation of an adaptive response by DCs.  The unchecked innate response only contributes to the vascular permeability and tissue damage that proves fatal. In short, there is a lot that we don’t know about Ebola immunopathology, but it is clear that those who recover are able to initiate a T cell response and the production of antibodies.

A vaccine for Ebola is still 5 years away or more, and is being actively pursued by researchers at the National Institute of Allergy and Infectious Diseases (NIAID) and Thomas Jefferson University. BioCryst Pharmaceutical in Durham, NC is pursuing a drug candidate, and Mapp Biopharmaceutical in San Diego is currently developing a monoclonal antibody cocktail in partnership with the Public Health Agency of Canada.

None of the above leads will help in the present epidemic. The current strategy is to provide medical care to and observation of those infected, and attempt to contain the spread of the virus any further.

rcotton

Rachel Cotton is a Senior Biological Sciences major in the Eck Institute for Global Health at the University of Notre Dame, where she conducts immunology and infectious disease research. She is Co-Editor in Chief of the undergraduate research journal, Scientia

 

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