BioRxiv – open access preprints

si-bioRxiv

For the vast majority of the general population, science is consumed via mass media head lines and carefully edited summaries of the research.

The result of this simplified end product is an ignorance of the process that researchers need to deal with in order to get their research in the public domain.

As part of our efforts to educate the general public about the scientific research of Parkinson’s disease, it is necessary to also make them aware of that process, the issues associated with it, and how it is changing over time.

In todays post, we will look at how new research reports are being made available to the public domain before they are published.


ibiology-preprints-1024x576

Getting research into the public domain. Source: STAT

Every morning here at the SoPD, we look at what new research has entered the public domain over night and try to highlight some of the Parkinson’s disease relevant bits on our Twitter account (@ScienceofPD).

To the frustration of many of our followers, however, much of that research sits behind the pay-to-view walls of big publishing houses. One is allowed to read the abstract of the research report in most cases, but not the full report.

Given that charity money and tax payer dollars are paying for much of the research being conducted, and for the publication fee (approx. $1500 per report on average) to get the report into the journal, there is little debate as to the lack of public good in such a system. To make matter worse, many of the scientists doing the research can not access the published research reports, because their universities and research institutes can not afford the hefty access fees for all of the journals.

Problem-infographic3

Source: Libguides

To be fair, the large publishing houses have recognised that this is not a sustainable business model, and they have put forward the development of open-access web-based science journals, such as Nature communications, Scientific reports, and Cell reports. But the fees for publishing in these journals can in some cases be higher than the closed access publications.

This is crazy. What can we do about it?

Well, there have been efforts for some time to improve the situation.

Projects like the Public Library of Science (or PLOS) have been very popular and are now becoming a real force on the scientific publishing landscape (they recently celebrated their 10 year anniversary and during that time they have published more than 165,000 research articles). But they too have costs associated with maintaining their service and publications fees can still be significant.

url

Is there an easier way of making this research available?

So this is Prof Paul Ginsparg.

Ginsparg_at_Cornell_University

Source: Wikipedia

Looks like the mad scientist type right? Don’t be fooled. He’s awesome! Prof Ginsparg is a professor of Physics and Computing & Information Science at Cornell University.

Back in 1991, he started a repository of pre-print publications in the field of physics. The repository was named arXiv.org, and it allowed physics researchers to share and comment on each others research reports before they were actually published.

The site slowly became an overnight sensation.

The number of manuscripts deposited at arXiv passed the half-million mark on October 3, 2008, the million manuscript mark by the end of 2014 (with a submission rate of more than 8,000 manuscripts per month). The site currently has 1,257,315 manuscripts that are freely available to access. A future nobel prize winning bit of research is probably in there!

Now, by their very nature, and in a very general sense, biomedical researchers are a jealous bunch.

For many years they looked on with envy at the hive of activity going on at arXiv and wished that they had something like it themselves. And now they do! In November 2013, Cold Spring Harbor Laboratory in New York launched BioRxiv.

maxresdefault

Source: BioRxiv

And the website is very quickly becoming a popular destination: by April 21, 2017, >10,000 manuscript had been posted, at a current rate of over 800 manuscripts per month (Source).

Recently they got a huge nod of financial support from the Chan Zuckerberg Initiative – a foundation set up by Facebook founder Mark Zuckerberg and his wife Priscilla Chan to “advance human potential and promote equality in areas such as health, education, scientific research and energy” (Wikipedia).

5677ff2b-be2c-49e7-b0cb-7e33c18149dd-1467045359144Chan-Zuckerberg-Initiative-1

Source: ChangZuckerberg

In April of this year, the Chan Zuckerberg Initiative announced a partnership with Cold Spring Harbor Laboratory to help support the site (Click here to see the press release).

So what is bioRxiv?

bioRxiv is a free OPEN ACCESS service that allows researchers to submit draft copies of scientific papers — called preprints — for their colleagues to read and comment on before they are actually published in peer-reviewed scientific journals.

Here are two videos explaining the idea:

Sounds great right?

To demonstrate how the bioRxiv process works, we have selected an interesting manuscript from the database that we would like to review here on the SoPD.

This is the article:

HEMMER

Title: In Vivo Phenotyping Of Parkinson-Specific Stem Cells Reveals Increased a-Synuclein Levels But No Spreading
Authors: Hemmer K, Smits LM, Bolognin S, Schwamborn JC
Database: BioRxiv
DOI: https://doi.org/10.1101/140178
PMID: N/A                   (You can access the manuscript by clicking here)

In this study (which was posted on bioRxiv on the 19th May, 2017), the researchers have acquired skin cells from an 81 year old female with Parkinson’s disease who carries a mutation (G2019S) in the LRRK2 gene.

Mutations in the Leucine-rich repeat kinase 2 (or Lrrk2) gene are associated with an increased risk of developing Parkinson’s disease. The most common mutation of LRRK2 gene is G2019S, which is present in 5–6% of all familial cases of Parkinson’s disease, and is also present in 1–2% of all sporadic cases. We have previously discussed Lrrk2 (Click here to read that post).

image1

The structure of Lrrk2 and where various mutations lie. Source: Intech

The skin cells were transformed using a bit of biological magic in induced pluripotent stem (or IPS) cells. We have previously discussed IPS cells and how they are created (Click here to read that post). By changing a subjects skin cell into a stem cell, researchers can grow the cell into any type of cell and then investigate a particular disease on a very individualised basis (the future of personalised medicine don’t you know).

nature10761-f2.2

IPS cell options available to Parkinson’s disease. Source: Nature

Using this IPS cell with a mutation in the LRRK2 gene, the researchers behind todays manuscript next grew the cells in culture and encouraged the cells to become dopamine producing cells (these are some of the most vulnerable cells in Parkinson’s disease). The investigators had previously shown that neurons grown in culture from cells with the G2019S mutation in the LRRK2 gene have elevated levels of of the Parkinson’s disease protein alpha Synuclein (Click here to read that OPEN ACCESS paper).

In this present study, the investigators wanted to know if these cells would also have elevated levels of alpha synuclein when transplanted into the brain. Their results indicate that the cells did. Next, the investigators wanted to use this transplantation model to see if the high levels of alpha synuclein in the transplanted cells would lead to the protein being passed to neighbouring cells.

Why did they want to do that?

One of the current theories regarding the mechanisms underlying the progressive spread of Parkinson’s disease is that the protein alpha synuclein is lead culprit. Under normal conditions, alpha synuclein usually floats around as an individual protein (or monomer), but sometime it starts to cluster (or aggregate) with other monomers of alpha synuclein and these form what we call oligomers. These oligomers are believed to be a toxic form of alpha synuclein that is being passed from cell to cell. And it ‘seeds’ the disease in each cell it is passed on to (Click here for a very good OPEN ACCESS review of this topic).

Mechanism of syunuclein propagation and fibrillization

The passing of alpha synuclein between brain cells. Source: Nature

There have been postmortem analysis studies of the brains from people with Parkinson’s who have had cell transplantation therapy back in the 1990s. The analysis shows that some of the transplanted cells have evidence of toxic alpha synuclein in them – some of those cells have Lewy bodies in them, suggesting that the disease has been passed on to the healthy introduced cells from the diseased brain (Click here for the OPEN ACCESS research report about this).

In the current bioRxiv study, the investigators wanted to ask the reverse question:

Can unhealthy, toxic alpha synuclein producing cells cause the disease to spread into a healthy brain?

So after transplanted the Lrrk2 mutant cells into the brains of mice, they waited 11 weeks to see if the alpha synuclein would be passed on to the surrounding brain. According to their results, the unhealthy alpha synuclein did not transfer. They found no increase in levels of alpha synuclein in the cells surrounding the transplanted cells. The researchers concluded that within the parameters of their experiment, Parkinson’s disease-associated alpha synuclein spreading was not detected.

Interesting. When will this manuscript be published in a scientific journal?

We have no idea.

One sad truth of the old system of publication is: it may never be.

And this illustrates one of the beautiful features of bioRxiv.

This manuscript is probably going through the peer-review process at a particular scientific journal at the moment in order for it to be properly published. It is a process that will take several months. Independent reviewers will provide a critique of the work and either agree that it is ready for publication, suggest improvements that should be made before it can be published, or reject it outright due to possible flaws or general lack of impact (depending on the calibre of the journal – the big journals seem to only want sexy science). It is a brutal procedure and some manuscripts never actually survive it to get published, thus depriving the world of what should be freely available research results.

And this is where bioRxiv provides us with a useful forum to present scientific biological research that may never reach publication. Perhaps the researchers never actually intended to publish their findings, and just wanted to let the world know that someone had attempted the experiment and these are the results they got (there is a terrible bias in the world of research publishing to only publish positive results).

The point is: with bioRxiv we can have free access to the research before it is published and we do not have to wait for the slow peer-review process.

And there is definitely some public good in that.

EDITORS NOTE HERE: We are not suggesting for a second that the peer-review process should be done away with. The peer-review process is an essential and necessary aspect of scientific research, which helps to limit fraud and inaccuracies in the science being conducted.

What does it all mean?

This post may be boring for some of our regular readers, but it is important for everyone to understand that there are powerful forces at work in the background of scientific research that will determine the future of how information is disseminated to both the research community and general population. It is useful to be aware of these changes.

We hope that some of our readers will be bold/adventurous and have a look at some of what is on offer in the BioRxiv database. Maybe not now, but in the future. It will hopefully become a tremendous resource.

And we certainly encourage fellow researchers to use it (most of the big journals now accept preprint manuscripts being made available on sites like bioRxiv – click here to see a list of the journals that accept this practise) and some journals also allow authors to submit their manuscript directly to a journal’s submission system through bioRxiv via the bioRxiv to Journals (B2J) initiative (Click here for a list of the journals accepting this practise).

The times they are a changing…


The banner for today’s post was sourced from ScienceMag

Advertisements

5 comments

  1. jonathanbromley

    This is obviously a brilliant development for researchers. However, I’m much troubled that unfettered public access to un-reviewed papers may be very harmful. The overwhelming majority of general-public readers (including myself!) lack the tools and training to decide whether these pre-publications are trustworthy or not; we certainly can’t attempt to reproduce results, and we may not even be able to access the references cited in such papers. There is a real danger here of “citizen science” turning into “angry mob science” if two things happen – both, I fear, very likely: first, unscrupulous researchers may use this preprint channel, along with energetic use of social media, to give a high public profile to poor quality work; and second, well-meaning but credulous members of the public may take inappropriate actions, or apply inappropriate pressure to public bodies such as the NHS, based on flawed material. In both situations, the power of social media can easily be used to give totally inappropriate weight to misguided and – in the worst case – dangerously ill-advised initiatives.

    The lack of widespread public access to published peer-reviewed papers is, indeed, a tragedy, and it must be fixed somehow. Nevertheless, we must not let our enthusiasm for open access lead us into a dangerous free-for-all.

    Like

    • Simon

      Hi Jonathan, thanks for your message. And yes, you are right. I agree that there is the very real possibility for a forum like bioRxiv to be abuse and misused (like the internet as a whole one could argue). But I note that bioRxiv state on their about page ( http://biorxiv.org/about-biorxiv ) that while the articles are not peer-reviewed, “all articles undergo a basic screening process for offensive and/or non-scientific content and for material that might pose a health or biosecurity risk and are checked for plagiarism”. The depth of such a screen will ultimately determine the success of this forum I suspect.
      But one disturbing feature, however, is that “Once posted on bioRxiv, articles are citable and therefore cannot be removed”. This is a flawed policy, one that could easily be abused in the ways you suggest above. I don’t think preprint manuscripts should be citable (except perhaps in a CV).
      Having said all of this, I would add that “angry mob science” already occurs – both on- and off-line. There are numerous open access journals that have their publications listed on Pubmed that have little grounding in proper science, making wild, unproven claims that folks in facebook group forums are already acting upon. The snake oil sellers pay the publication fee and hey presto they are suddenly legitimate. Is bioRxiv going to add fuel to the fire? Probably. But what would be the alternative be? A return to the old fashioned status quo? Access to research being limited to just scientists and the general public being given yet another “Cure for PD close” headline? And an ever widening gulf between the two parties? Would the well-connected PD community accept that? It will be interesting to see if the Chan Zuckerberg initiative makes any policy suggestions in this regard, or whether they will simply be a silent partner.
      I don’t know the answer either. I agree with your “lack the tools and training” concern though and hope that what we do here might make a little bit of difference. Thanks again for the comment. It adds a nice counter argument for the post.
      Kind regards,
      Simon

      Like

  2. lionelljp

    Simon, this article is excellent news – okay as you say many of these articles that will pass through this system may never make it to full-fledged maturity as peer-reviewed papers that have been published, but we all will have a much better chance of knowing what we are missing if we can keep up with the information flow. Up to now we did not know what we did not know (confused? I think it makes sense!) but bioRxiv will give us a handle on knowing more. Simon, thanks for this resource which will be very useful.

    Like

    • Simon

      Glad you liked the post Lionel. Yes, it is a very useful tool if used wisely, though I suspect most of the general population will continue to focus solely on the mass media headlines. I mentioned it here just to make folks aware of it and the brutal process via which the research has to go through to enter the public domain. I like to think bioRxiv is a step forward, and it will be interesting to see what comes next. Thanks for your comment.
      Kind regards,
      Simon

      Like

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s