Why are papers on rare diseases from the FDA and NIH behind journal paywalls?

Hypothetically, lets just ask the question what would you do if you, a family member or a friend was diagnosed with a rare disease.. what would you do? If there was no cure where would the first place be that you would look for guidance? Wikipedia, Google probably would be first then these would point you to research papers. The scientists among you would go to PubMed straightaway and try to find what research had been done, track down the scientists etc. try to make their way through the papers on the topic and then maybe follow up by emailing or calling the researchers with questions.

What if you are new to this whole science endeavor, all of a sudden you are finding lists of relevant papers in PubMed, but when you click on the links to get the article you are sent to a publisher and asked to fork out cash to read the work. Then what do you do? I have heard and read about this scenario over and over again. I thought It was time to dig deeper and a single email triggered it.

Today I was sent a link to a couple of rare disease papers, both by different groups, both in Nature Reviews Drug Discovery from 2010. One came from a company and the other was from a group at the FDA. The paper from the company was behind a $32 paywall while the one from the FDA was accessible upon registration. This got me thinking, why should I even have to register to get access to papers that were likely written on government time, paid for by our taxes and yet published in a journal in the UK that presents a barrier to instant download?

I dug deeper to see how many other papers of potential interest were behind different journal paywalls. I found the following in an admittedly very quick search on the same group of authors. All locked behind paywalls.

Brief Bioinform. 2011 Jul;12(4):341-5. doi: 10.1093/bib/bbr006. Epub  2011 Feb 26.

Database identifies FDA-approved drugs with potential to be repurposed for treatment of orphan diseases.

Clin Pharmacol Ther. 2010 Oct;88(4):449-53. doi: 10.1038/clpt.2010.193.

The impact of the Orphan Drug Act on the development and advancement of neurological products for rare diseases: a descriptive review.


Office of Orphan Products Development, US Food and Drug Administration, Silver Spring, Maryland, USA.
Nat Rev Drug Discov. 2010 Jul;9(7):519-22. doi: 10.1038/nrd3160. Epub  2010 Jun 7.

Emergence of orphan drugs in the United States: a quantitative assessment of the first 25 years.

Muscle Nerve. 2010 Jun;41(6):740-5. doi: 10.1002/mus.21623.

Duchenne muscular dystrophy: Drug development and regulatory considerations.

Nat Rev Drug Discov. 2010 Jan;9(1):84. doi: 10.1038/nrd2546-c1.

Orphan products: an emerging trend in drug approvals.

Melanoma Res. 2009 Feb;19(1):58-60. doi: 10.1097/CMR.0b013e32831ef262.

Primary melanomas of the esophagus and anorectum: epidemiologic comparison with melanoma of the skin.

J Bone Joint Surg Am. 2006 Mar;88(3):503-7.

Autologous cultured chondrocytes: adverse events reported to the United States Food and Drug Administration.

J Am Acad Dermatol. 2005 Sep;53(3):407-15.

Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases.

I thought I could probably do the same search for the NIH and look for topics relevant to rare diseases and find papers behind firewalls without a PMC version as well – here is one I came across last year in an ACS journal as an example. CMT1A is a rare disease, the gene was identified over 20 years ago and this was documenting probably the first high throughput screen of compounds that could modulate the disease. But you would have to pay $35 for 48h of viewing – while ACS members get a reduced price!
ACS Chem Biol. 2012 Jul 20;7(7):1205-13. doi: 10.1021/cb300048d. Epub  2012 May 2.

Identification of drug modulators targeting gene-dosage disease CMT1A.


National Center of Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland 20892, United States.

Lets spread the net wider and further..to the director of the NIH, Dr. Francis Collins – anyone can do a search on PubMed for Collins FS and this returns a huge list of publications (> 500 currently)..Lets look at some of the recent ones at the time of writing that relate to rare diseases – some of these may have come from other labs but Dr. Collins is a co-author and at the time of writing the ones below are behind a paywall.
Science. 2013 Mar 1;339(6123):1036-7. doi: 10.1126/science.1236194. Epub  2013 Feb 21.

Research funding. A framework for decisions about research with HPAI H5N1 viruses.


National Institutes of Health, Bethesda, MD 20892, USA. pattersa@od.nih.gov

Genome Res. 2013 Feb;23(2):260-9. doi: 10.1101/gr.138032.112. Epub  2012 Nov 14.

Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome.


Program in Systems Biology, Department of Biochemistry and Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA

Sci Transl Med. 2011 Jul 6;3(90):90cm17. doi: 10.1126/scitranslmed.3002747.

Reengineering translational science: the time is right.


Office of the Director, National Institutes of Health, Bethesda, MD 20892-8004, USA. francis.collins@nih.gov


Sci Transl Med. 2011 Jun 29;3(89):89ra58. doi: 10.1126/scitranslmed.3002346.

Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.

Sci Transl Med. 2010 Jun 23;2(37):37cm18. doi: 10.1126/scitranslmed.3001235.

Patient-Centered Outcomes Research Institute: the intersection of science and health care.

So here is a challenge. If the director of the NIH can insist that all rare disease (or for that matter neglected disease) research published by government employees is open access then I think that it will send a clear message to others outside that are government funded to do the same. I feel pressure as I am writing this to make more of my work open access and only a part of what I have done recently is govenment funded research..
So now put yourselves in the place of a patient or parent trying to find out about the rare disease diagnosis they have just been given, searching desperately for reliable scientific information, looking for hope and what do they find? A publisher sticking them for $30-$35 to see what they have been seeking. And then they look at the address of the authors and see the abbreviations NIH or FDA, they get the sinking feeling and you know the words they will utter, surreal, no this is reality.

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