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Sunday, January 05, 2014

The Power of Science

I've often cited the Begley and Ellis Nature paper, "Drug development: Raise standards for preclinical cancer research".  Glenn Begley has graced Xconomy with an article on scientific reproducibility. 

The concept that science must be reproducible before you can call it science is a slippery slope to some. A comment from the Nature webpage listed above:
The claims presented here are pretty outlandish. Particularly relevant to "Hematology and Oncology" we now know that mice housed under different conditions with different microflora can have vastly different outcomes in any model, not just cancer. To suggest academic incompetence or outright unethical behavior is offensive, and is a particularly narrow view of why experiments are difficult to reproduce. Further, as indicated in Table 1, the entire definition of not-reproducible hinges on a priori profit motive of "robust" differences (whatever that means). There is always room for improvement in science, but this entire article is disingenuous and belittling to those of us who are on the front lines.
To this I would respond:

"The manager accepts the status quo; the leader challenges it."Warren G. Bennis

Here is the enemy. Feynman described the mouse maze experiment where confounding factors lead many researchers astray. Finding out where we can go astray is an important part of the scientific method. If you don't rule out as many confounding factors, you are subject to making mistakes like those made by not knowing the effect of microflora on mouse experiments. Will a study on microflora get you a tenured position or will it make you a thorn in the side of the scientists who are more concerned about their career in cancer research? Most likely the latter is true. It is the responsibility of leadership to create a more welcoming place for real science, that may not jibe with the career/corporate aspirations of less rigorous scientists.
It is important to realize that this debate, highlighting the deficiencies our scientific process, is taking place openly within the scientific community. This is a sign of the strength of our scientific system.
That is a very important point. People are embracing the conversation about our shortcomings in science. We need more humility, more honesty and less arrogance. A call for increasing the rigors of our soft science is only going to be a positive for the good name of science. The people who will be hurt by a push in the direction of the scientific method are those who do not appreciate what it can do.

The above commenter may believe that any dissenting view of modern science is heresy. (I don't want to create a straw-man argument, thus he may...) If the argument against increasing reproducibility, increasing transparency, and increasing rigor, is that it would make working in science too hard, then I would argue that the power of real science is misunderstood. Your boss may want to see a positive result from your mouse study on his desk prior to his/her next board meeting. You may have just discovered that the microflora is confounding the reproducibility of your experiments. What do you do?  Is it wise to assume that everyone believes that the newfound knowledge of the microflora will be received with open arms from the guy who didn't ask you to look into such details? In this case, the scientific method is in opposition to the political method. The Machiavellian tactics you employ to advance or simply to keep your job are often times jeopardizing future research, yours and those in your field.

The questions Glenn Begley asks:

What constitutes reproducibility?
What, if anything, has changed?
What is driving this?
What is being done and where will this take us?

What Glenn Begley is doing is very important for others who currently work in, or one day hope to work in science.
The majority of scientific discoveries in the biomedical sphere should be sufficiently rigorous and robust to allow other investigators to build on that work and move the field forward. Hopefully the changes instituted as a result of this debate will help further strengthen our discovery processes. - Glenn Begley
Status quo, you know, is Latin for 'the mess we're in'.
Ronald Reagan
If there is dissatisfaction with the status quo, good. If there is ferment, so much the better. If there is restlessness, I am pleased. Then let there be ideas, and hard thought, and hard work. If man feels small, let man make himself bigger.Hubert H. Humphrey 

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