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The Antibody Reproducibility Crisis: Part 2

By: Luis Chiriboga, PhD, HT(ASCP), QIHC(ASCP)


In Part 1 of this series, Dr. Chiriboga discussed the growing problem in the research community, of not being able to reproduce scientific studies, specifically how lack of standardization in antibodies contributes to this problem. Read Part 1 here. Part 2 will discuss what is driving this problem, and what this problem means for the histology profession.


What is driving this problem?

Despite the broad scientific community response, the basic question remains: What is driving the problem, especially when it comes to antibodies? Is it an industry, academic or government problem? Is it lack of education and training or just standardization and quality control? Has dwindling research funds or the “publish or perish” mentality resulted in investigators circumventing good laboratory practices in order to drive their careers?


In 2013, the Global Biological Standards Institute (GBSI) formed with the sole purpose of promoting the use of best practices to improve the quality of life science research. In 2014, GBSI formed the Research Antibodies and Standards Task Force. In order to better understand the forces driving the problem, the Task Force created an anonymous online survey that received just over 500 responses [5]. The responses, stratified based upon respondent tenure, showed one distressing trend. Almost a third of junior faculty (<5 years tenure) do not have their research antibodies validated. When asked why, they said they “do not see the need”!



This reveals a problem, since less than 10% of senior faculty responded similarly. More recently, a different survey of 3200 scientist found some cracks in the “mentor-mentee” training relationships that may underscore the issue [6]. Close to 95% of PI’s agreed with the statement that they “check the experimental design done by their group”. However only 60% of non-PI’s agreed with the statement. Similarly, 90% of PI’s said they “looked at raw data” while fewer than 60% of their staff agreed. The significance? These are two vital steps in the scientific method.


What does this mean?

The message promoting good laboratory practices may not be reaching the next generation of scientist.

Of course this is not universal, as always there are going to be labs that do a better job and those that do not. However, the trend is clear. Communication is key, reliance on “previous results”, “manufacturer’s data” and on “kit” reagents can create a presumption of legitimacy that overtakes good laboratory practices. Insufficient emphasis is placed on the responsibility to authenticate each step for the sake of time, money and perhaps prestige. However, the take home message is not to make biomedical research more laborious and dense, quite the opposite; instead, to try to make it simpler and robust so that that the time and money invested, results in advancing the human condition as well as creating successful career scientists.


References

1. Begley, C.G. and L.M. Ellis, Drug development: Raise standards for preclinical cancer research. Nature, 2012. 483(7391): p. 531-3.

2. Bradbury, A. and A. Pluckthun, Reproducibility: Standardize antibodies used in research. Nature, 2015. 518(7537): p. 27-9.

3. Collins, F.S. and L.A. Tabak, Policy: NIH plans to enhance reproducibility. Nature, 2014. 505(7485): p. 612-3.

4. Freedman, L.P., I.M. Cockburn, and T.S. Simcoe, The Economics of Reproducibility in Preclinical Research. PLoS Biol, 2015. 13(6): p. e1002165.

5. Freedman, L.P., et al., The need for improved education and training in research antibody usage and validation practices. Biotechniques, 2016. 61(1): p. 16-18.

6. Van Noorden, R., Some hard numbers on science's leadership problems. Nature, 2018. 557(7705): p. 294-296.

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