“The very word “secrecy” is repugnant in a free and open society; and we are as a people inherently and historically opposed to secret societies, to secret oaths and to secret proceedings. We decided long ago that the dangers of excessive and unwarranted concealment of pertinent facts far outweighed the dangers which are cited to justify it.”
This portion of a famous speech given by President Kennedy frames the problems we are facing not only in our government, but in biomedical research. These problems are caused by the lack of transparency and traceability under which the biomedical research industry operates, exemplified by research use antibodies.
Tim Bernard, head of the biotechnology consultancy Pivotal Scientific in Upper Heyford, UK says that the 2 million antibodies on the market probably represent 250,000–500,000 unique ‘core’ antibodies. If what Tim Bernard stated in this Nature article is true, then every antibody manufactured will be relabeled an average of 4 to 8 times. This means that the average antibody is available on at least 4 to 8 different vendors' catalogs, which appears to researchers as unique products offered by each vendor. In some cases, the same antibody can be offered in a dozen or more catalogs under different brand names. In the case of the first example presented above, the researcher buys all available products on the market to find out that only a few are unique.
This would not necessarily be an issue if there was not an all-time low public confidence in the findings published in scientific journals. A report released in 2012 stated as little as 11% of the most important published biomedical research could be reproduced by the industry's top scientists at the biotech giant, Amgen, which caused great alarm in the scientific community. A year prior to the Amgen report being released, a team at Bayer HealthCare in Germany supported the claim of low reproducibility with their conclusion that only about 25% of published preclinical studies could be validated to the point at which projects could continue.
It is the relabeling of scientific products which eliminates traceability for the future reproduction of scientific work, and is a business practice consistently used by most vendors. Even though this business practice is at the heart of the dilemma, it is rarely mentioned as a factor by many of the industry's key opinion leaders. Dr. Jan Voskuil, the former CSO of Everest Biotech and founder of Aeonian Biotech, makes it clear that manufacturers are under a "gag order" to not identify themselves as the makers of the products they sell to the vendors.
Because there is not traceability there is also no real accountability.
The vendors keep up the appearance that they themselves are the primary source of all their antibodies. This enables them to keep QC data on the product sheet that were generated many years ago, thus keeping the sales going, while the actual antibody that generated these data may have sold out and has been replaced by successive other batches (from different animals) and the current batch on sale may no longer be able to generate such data at all. Vendors accrue data from their own customers or from their own QC department, thus making the OEM product look unique. Even monoclonal antibodies that are theoretical genetic clones and therefore identical throughout time, suffer from batch-to-batch variations, but not to such severe extent as some types of polyclonal antibodies where the genetic variation is greater. Nonetheless, certain hybridoma clone numbers are still being used for decades while, just like with all cell lines, hybridomas cannot be the same after so many passages.
All the mess is amplified due to the vast network of vendors obtaining each other’s catalogue items. Consequently, the same antibody starts to occur several times in one catalogue. We can now understand how the practices of an industry undermine scientific pursuits.
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The reaction to these reports discovering the low levels of reproducibility in preclinical research has been rightful concern and alarm at the highest levels of the National Institutes of Health (NIH), which issued new criteria for grant reviews aimed at bolstering the reproducibility of NIH-funded research. Another direct result of this “Reproducibility Crisis” was the establishment of the Global Biological Standards Institute (GBSI) which released a study in the journal PLOS "The Economics of Reproducibility in Preclinical Research" which states $28 billion is spent in the United States each year on biomedical research that can’t be reproduced by other researchers. GBSI has now assembled committees to mandate new guidelines that all companies selling antibodies must follow.
Interestingly, members on these committees are comprised of the industry’s top companies which also practice the relabeling of other manufacturers' products. Some believe this may create a barrier to competition with those setting the guidelines eliminating smaller companies from the marketplace. One could draw a correlation with the ushering in of the “Patriot Act” after the terrorist attacks on “9/11”. It was passed into law under the guise for addressing holes in our national security, but has since been discovered to have turned over individual rights to the State. Is the GBSI promoting an enormous problem only to quickly manufacture a solution that will only serve to reinforce the powers that be?
The solution is quite simple, but extremely difficult to implement. It is like meditation where the act only requires you to stop thinking and only be aware of your bodily sensation--simple in theory, but very challenging in practice. Here, in preclinical research we need a platform that identifies original manufacturers and makes their products, i.e. antibodies, available in affordable sample amounts for parallel testing. The platform would also allow for feedback from researchers regarding their experiments and product performance to be submitted in the form of a review. These reviews would be interactive allowing manufacturers to offer guidance and optimization of protocols used. If we can create an egalitarian system in preclinical research, then maybe it will spread to other industries and the rest of the world. That’s how big this really could be if we get it right.
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