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Wednesday, December 17, 2014

How Can You Not?

This is a clear case of a Cargo Cult leadership. Quality control/assurance is not possible at the NIH? The elephant in the room is how so many researchers get the results they seek regardless of what cell lines the use.

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Monday, September 01, 2014

Optimism Is Essential For Our Success?

“I have always believed that scientific research is another domain where a form of optimism is essential to success: I have yet to meet a successful scientist who lacks the ability to exaggerate the importance of what he or she is doing, and I believe that someone who lacks a delusional sense of significance will wilt in the face of repeated experiences of multiple small failures and rare successes, the fate of most researchers.” ― Daniel Kahneman, Thinking, Fast and Slow
This is probably the most profound quote from 'Thinking Fast and Slow', pertaining to the CCS. However much I disagree with the concept of optimism, a human emotion, being essential for success in science, the statement is true. The fate of most researchers is to wilt in the face of repeated experiences of multiple small failures and rare successes. We get beat down from our inability to impress with our research. Just ask the 660 Amgen employees in the Seattle area who are facing an unknown future. Our version of the scientific method does not seem to work as well as other scientists. In order to succeed in a science career, we have to appear optimistic. I, the CCS, am not an optimist. I believe in the power of the negative. If I put my hand on a red hot skillet, I accept the negative burst of pain that prompts me to relocate my hand to prevent permanent damage. Negative outcomes are merely perceptions of the viewer. Any outcome is a clue for the researcher. You can choose to accept what you see or you can try again hoping for a different outcome. Success occurs when you accurately explain an outcome.
That is the idea that we all hope you have learned in studying science in school--we never say explicitly what this is, but just hope that you catch on by all the examples of scientific investigation. It is interesting, therefore, to bring it out now and speak of it explicitly. It's a kind of scientific integrity, a principle of scientific thought that corresponds to a kind of utter honesty--a kind of leaning over backwards. For example, if you're doing an experiment, you should report everything that you think might make it invalid--not only what you think is right about it: other causes that could possibly explain your results; and things you thought of that you've eliminated by some other experiment, and how they worked--to make sure the other fellow can tell they have been eliminated.
The person who can do this and not suffer the consequences of seeming less than optimistic is having a successful science career. The scientist who feels pressure to exaggerate the importance of their work is not as successful as they let on. Lysenko, for example, was a highly successful scientist, if ones rank in the hierarchy in which you serve is the criteria for success. Dipak Das and Diederik Stapel are examples of college professors who have a history of successfully getting their work published. Yet history has to paint a picture of unsuccessful scientists. Their work is not useful. So what is success? Does it require optimism? Certainly Lysenko, Das, and Stapel knew well the politics of a success career. If they could have been better researchers, they would have used the truths they uncovered to accomplish the same success they achieved through deception. Any BS'er will tell you, the truth is a better weapon than a falsehood. The truth does not have to be guarded and kept behind the curtain of Oz. Any time an exaggeration is used, the scientist must be careful not to cross that line Das and Stapel crossed.
“A reliable way of making people believe in falsehoods is frequent repetition, because familiarity is not easily distinguished from truth.” ― Daniel Kahneman, Thinking, Fast and Slow
So sayeth Dr. Kahneman.
We've learned from experience that the truth will come out. Other experimenters will repeat your experiment and find out whether you were wrong or right. Nature's phenomena will agree or they'll disagree with your theory. And, although you may gain some temporary fame and excitement, you will not gain a good reputation as a scientist if you haven't tried to be very careful in this kind of work. And it's this type of integrity, this kind of care not to fool yourself, that is missing to a large extent in much of the research in cargo cult science.
So sayeth Dr. Feynman. A successful science is the product of many individuals who work under the title of "scientist". A "successful scientist" is one of many such individuals who may be contributing positive or negative things to the science. And the truth will come out. A truly successful scientist is one who gains a good reputation in the long run. Our ideas and theories are bigger than our careers, in the long run. What determines a successful scientist is the science behind the rhetoric.

Tuesday, August 05, 2014

Location Location Location

The constant job loss is a part of the cargo cults. They hire with little understanding of what is really needed. In time the lack of cargo leads them to the path of laying off unproductive members of the tribe. Those who make the decisions have to retain their own services because they have a different function. It is their job to keep the cult alive so new ceremonies can be attempted. What Amgen did with their layoffs is no different than all of the other layoffs. In New Jersey, Roche has left enough empty laboratory/biopharma space to fill every floor of the Empire State Building. Seattle has nothing on the state of New Jersey.
Five years ago, Roche acquired Genentech, moved its management to San Francisco and started to slowly withdraw from New Jersey. That's a pretty typical story for what's been happening in the state. In the past 20 years, New Jersey went from having more than 20 percent of U.S. pharma manufacturing jobs to less than 10 percent.
The state of Washington or New Jersey is not the state we need to dissect. The state biopharma is the problem. When it comes to our hopes and dreams about jobs and useful drugs it is going to take more than new surrounding and new money. The constant relocation of the jobs and the shuffling around of the workforce is not working. It contributes to a weaker and weaker workforce. It leads to Yes-men and desperate researchers willing to say what is needed to work another day. If we were to look carefully at the state of biopharma and their scientific method, we would find that it does not vary from one place to the next. Likewise nor do the layoffs.
"Essentially, every time there's a merger or one company acquires another company, there's a reduction in force, and there's been furious mergers and acquisitions in the pharma industry, particularly over the past 10 years," says James Hughes, dean of the school of public policy at Rutgers.
The furious mergers and acquisitions are work functions that keep the leadership away from the higher risk activities of conducting research. It is hoped that someone else will come up with something in the pause created by merging companies, laying off people and articulating the way forward. History has shown that this is not a very effective method.
Business professor Erik Gordon of the University of Michigan says cutting-edge research isn't being done on closed campuses in the suburbs anymore. "The new innovation in biotech, in genomics is happening elsewhere. It's happening in places where there are graduate educational institutions that have research faculty doing that, and New Jersey really doesn't have that," he says.
Again, we see this concept that cutting edge research is done only at certain locations. We've even been given an explanation for why that is. You need to be close to graduate education institutions that have research faculty doing new innovation in biotech and genomics! Take that Rutgers. Serepta had this concept long ago. They moved from Oregon to Bothell WA then to the Boston area. They hired and fired a new Chief Scientific Officer and the CEO and Chairman of the Board had a public spat. Those who think long and hard about what science is know that it is not something that only occurs at certain locations. The natural world can be observed anywhere. A laboratory in Seattle versus a lab in New Jersey or China, is no different. When we want to purify DNA will will all go to the internet to purchase a kit from Invitrogen or some other favorite kit provider. When we want to buy an HPLC we will hold meetings and decide upon our favorite HPLC provider. All HPLCs work the same. They also work the same in Seattle, New Jersey and China. This is the beauty of science. If you are thinking about it correctly, you are thinking about things that do not change from location to location. It can be done anywhere.
"What really sets this site apart is its location," says Tom Stanton of Jones Lang LaSalle, the real estate firm marketing the site. The site is so big that to show it off, Stanton needs a minibus. Looping through a parking lot with thousands of empty spaces, Stanton stresses how close the campus is to Manhattan, Newark's airport and public transit. "Hiring young, talented people is really important to these companies. And that population of upcoming talent is more into the city life," he says.

Sunday, August 03, 2014

Positively Sink'n Think'n About Amgen Seattle

An Amgen spokesman told Xconomy its Seattle R&D site and Bothell manufacturing sites employed 660 people combined, with 430 more in Colorado. The facilities will be closed by the end of 2015.
I've extracted this bit of news from an article on Xconomy. The rest of the article depicts the upside that remains in Seattle.
When asked for his reaction to the Amgen news, Washington Biotechnology & Biomedical Association president and CEO Chris Rivera said, “In a word, disappointing.” But Rivera adds he is optimistic that the employees who don’t relocate—Amgen said it would shift jobs to its Cambridge, MA, and San Francisco Bay Area locations—should be able to find jobs in Washington state if they want to.
The Seattle Times reported Riveras' thoughts on the matter this way:
Chris Rivera, president of the Washington Biotechnology and Biomedical Association, said that while the news was a letdown given Immunex-Amgen’s history in Seattle, he is “pretty confident” those employees who want to stay here will be able to find a job in the sector. “There are plenty of opportunities here,” with about 190 biotechnology and pharmaceutical companies in the area, he said.
Next we hear from Bob Nelsen of ARCH Venture Partners, a longtime investor in the Cargo Cults of Seattle: "Amgen’s departure is not good, but the area’s strength in various disciplines will make up for it in the long run.” Oh sure, Amgen in Seattle had 1600 employees in 2004. In 2015 they will have zero. The 750,000 square feet facility will now go on Craigslist perhaps. 'R&D space available. Nice view! DNA bridge included!' The unemployed will take their resumes, many of which will list a degree from UW and one narrowly defined job at Amgen, and go find those jobs that Rivera and Nelsen believe exist. The cargo cults are going to be just fine. The truth is that this is bad. Really bad. We haven't learned anything nor have we admitted that this failure is something worth a concerted effort to prevent in the future. We cannot look past this spectacular failure of the biggest deal in the history of Seattle biotech. The demise was not sudden. There were 1600 jobs in 2004 and only 610 left to eliminate in 2014. The demise was a long slow process. Only one decade after the most grandiose R&D cargo cult was finished and fully staffed, it goes to the Seattle Biotech graveyard. We have seen the loss of many companies large and small. From the tiny 3 people companies at Accelerator to the larger implosions of Zymogenetics and Icos, Seattle biotech workers have had to exist in a minefield. Those losing their jobs must share in the culpability of this minefield. They are cargo cult tribesmen who do not want to speak of that lack of cargo planes landing on their runway. The optimism is always there. The cargo? Now they must be moving on to man the watch tower at the next airport. Once again there will be no gathering of "talent" to put down on paper what was learned. The only writing that will take place comes in the form of CVs depicting only positive information. The leadership that survives will rest assured that they have made the prudent decision and that ten years from now, all will be better. This is the problem with positive thinking. Nothing is gained. As one soon-to-be ex-Amgen researcher said, "I understand from a business angle but I think it is shortsighted." Really? You understand cutting out R&D from a science based company where the kind of research you do can take decades to complete? They shut you down in ten years! Get mad! This is a raw deal. Those who conduct research surely have a thing or two to say about a ten year period where 1600 people lost their jobs. Something was not going well. What was the negative side of your work? Why do you think the executives did not see the value in what you did for their company? Times like these require everyone to face the facts, just as the leadership at Amgen has had to face facts. The value of R&D is just not there. Either it is not very scientific (as the Amgen Study reported) or the leadership is missing its point. Why not make a decision yourself then? Speak out about what you did. I once interviewed for an RNAi job at the Seattle Amgen facility. I learned that it was an RNAi job while on the interview. I told them I would not work with RNAi. We chatted politely but the interview was over for all intents and purposes. I shared what I experienced with RNAi and why I did not believe in the future of the technology. Since then I have witnessed one RNAi company fail after another. Serepta continues to crumble. I gave up biotech entirely in 2010 but I remain loyal to the cause. Not in a positive way like Rivera and Nelsen. I am one of the guys who would have lost his job had I got the RNA job at Amgen. I saw the same value then as Amgen executives see now. The people I interviewed with at some point between my interview and now have lost their jobs. The value of the work we were talking about that day has been decided. It is worth nothing. Now what can we do to find value in ourselves? How can we work towards a brighter future for the next generation or will it be up to them to improve upon what we've been begun? What will become of the unemployed in the next few years? There are many questions but no one is asking them. We don't want to seem negative.

Sunday, July 20, 2014

The Trouble With Positive Thinking/Falling From Grace

What is the difference between purposely deceiving an audience and accidentally deceiving yourself? My hero James Randi points out that a magician is the only honest professional, in that s/he sets out to deceive you, tells you that they are going to do it, then does. Contrast that with an advertising professional. They are like magicians except they do not want you to know they are trying to deceive you. A true skeptic however, knows the score. We set our minds to the task of finding the deception, just as Feynman did in the Cargo Cult speech when discussing the Wesson Oil ad campaign.
The easiest way to explain this idea is to contrast it, for example, with advertising. Last night I heard that Wesson oil doesn't soak through food. Well, that's true. It's not dishonest; but the thing I'm talking about is not just a matter of not being dishonest; it's a matter of scientific integrity, which is another level. The fact that should be added to that advertising statement is that no oils soak through food, if operated at a certain temperature. If operated at another temperature, they all will--including Wesson oil. So it's the implication which has been conveyed, not the fact, which is true, and the difference is what we have to deal with.
Imagine Feynman standing in front of the Wesson Oil section of your local grocery store. "Hey, that oil is no different than this one." The would-be purchasers of Wesson Oil would think he is a nut. Yet he speaks the truth. Those who choose to deceive, on the other hand, positively convince the consumer through tv commercials with attractive middle class people that Wesson Oil is a wise choice. The facts thus take a back seat in influencing decisions when more pleasant narratives are in place. Our irrational behavior is our achilles heal. To make matters worse, we have been conditioned to believe that we cannot be so easily fooled. To consider the notion would be to admit a naivete that we don't want to believe. The leaders of biotechnology/pharmaceuticals likewise do not entertain the idea that their selection process has ever been faulty. They have selected for the best and the brightest individuals. Please ignore our history of successes and failures. These individuals simply cannot entertain the notions that luck has anything to do with the fact that they are still employed. Yet lately, even the positive thinkers are starting to have doubts about their chosen profession. In this article we see that people are starting to feel as if we are falling from grace. Grace? Were these people being positive to avoid getting weeded out of our industry? I began this blog with the exact opposite notion about myself and my cohorts. I felt that we were merely watchtower employees of a cargo cult. The layoffs were a part of my industry before I began and after I left. Every time I lost a job I felt that, while I had learned something, the world had not gained much from our efforts. I did not get down on myself because I had learned something. I had grown and every time I found myself at the next cargo cult, I would one day read about the demise of the last one. I made no excuses for myself nor the cargo cult. I failed and they failed because we did not take science seriously. We favored our careers over the thing that made our careers possible. We were standing on the shoulders of giants waiting for them to take us to the land of milk and honey. They didn't budge! As I come back to this blog it is with the purpose to attack the positive thinking that has created four decades of nowhere careers, bad science and the loss of a few hundred billion dollars. In his book, "The Antidote, Happiness for People Who Can't Stand Positive Thinking" Oliver Burkeman describes a study where researchers at a molecular biology lab at UC Berkely were themselves studied. Each time they encountered a result that they had not expected, they first questioned themselves. What had they done wrong. The thought that what they were seeing was to be taken seriously and used to move forward was not entertained. They moved forward in pursuit of the positive result, the one they designed into the experiment. These scientists aspire lead their own labs or groups within biopharma. They want a job! It's not getting harder to have a job as the "Falling From Grace" article suggests. It remains hard to keep a biopharma job. What we are doing is not working. Yet we don't give up. We fight to keep our employment because that one project is your whole job. This is not sustainable. Fight to remain in research, not just the research project you are on. Admit defeat when you know it's time to move on. And move on! It is a cargo cult science out there and that is the problem. Bend over backwards to be honest and leave your hopes and dreams at the door. The scientific method will lead you in directions your positive thinking irrational mind can't imagine.

Friday, January 31, 2014

Biotech Royalty

David Blech earned the title "The King of Biotech". Armed with a Masters degree in Music Education, he became a member of the Forbes 400 investing in companies like Genetic Systems Corporation, Icos, and Celgene. In 1990 he founded D. Blech and Co., a registered broker-dealer involved in underwriting biotechnology issues. On September 22, 1994 the company was deep in debt and ceased operations due to net capital rule violations. The day is known as Blech Thursday.
The uniform net capital rule is a rule created by the U.S. Securities and Exchange Commission ("SEC") in 1975 to regulate directly the ability of broker-dealers to meet their financial obligations to customers and other creditors. Broker-dealers are companies that trade securities for customers (i.e., brokers) and for their own accounts (i.e., dealers).
Blech was given a five year probation sentence in 1998 for criminal fraud. In May 2012 he pleaded guilty to manipulating shares of biopharmaceutical companies Pluristem Therapeutics Inc and Intellect Neurosciences Inc in 2007 and 2008. 

The Cargo Cult message of the story is that success in biotech financial matters does not require a PhD from MIT. It does not require bend-over-backwards scientific honesty. It requires the mind of a gambler. Remember the successes, but not the failures. Remember random events around your successes and tout them as skillful tricks of the trade you are in. 

In Seattle there is a building with four numbers in front. 

Inside this building are people who have chosen the same career path as David Blech. Carl Weissman and Steven Quay have been at the helm of several costly biotech investment decisions. Neither has found themselves on the Forbes 400 but they have had lucrative careers in biotechnology. The investments they have attracted have not been lucrative. Weissman is now the former CEO of Accelerator and Quay is in charge of a sinking ship known as Atossa Genetics. 

I don't want to go into further details about these investment opportunities. I've written about them before. Each man is a leader, as defined by the terms of a CEO. You are investing in them and the decisions they make with your money. Like David Blech, they are not scientists, as defined by the terms of a CSO. They seek money and use it to build biotechnology companies. The science is none  of their  business. Their careers have seen hundreds of millions come and go. They want you to focus in their ability to make the money come, never mind how it goes away.

The takeaway from  Blech, Weissman and Quay is that leadership matters. What makes a good biotech leader? In 1992 David Blech would have been considered a great leader. In their rise, Weissman and Quay were considered worthy of stewardship over millions and millions and the careers of many very smart people. In the ruins of their management is the loss of that money and the ruined careers of too many scientists. True, Blech (the music education master) started companies that made money and continue to do so. But he did not do the work that made these companies long term successes. These three individuals are prime examples of the short term mentality. Start company, get out before the fall. They are prime examples of why we need standardization, certified laboratories with certified lab workers. We need to create an career path for scientists who have the power of science to help investors avoid the song and dance of these three men. One of these men is in prison, one is looking for work, and one is draining $600,000 per year (CEO and CSO salaries for he and his wife) until the latest round of financing is depleted. Be assured that all three will continue to fight for their livelihood and raise money to spend on short term money making biotechnology companies.  

There is a little bakery on the bottom floor is 1616 Eastlake called Grand Central Baking Company. They are the most profitable company that has ever done business out of 1616 Eastlake. They have outlasted all of the Accelerator companies. They have a passion for what they do. 
More than two decades after our founder Gwen Bassetti introduced the Como loaf in Seattle’s historic Pioneer Square, we are still locally owned, led by a unique mixture of family and friends, and dedicated to the craft of artisan baking.
Biotech royalty, like Bech, Weissman and Quay, have a passion for the deal. They love being the biggest boy at the big boy table. But this isn't the craft that makes biotech success stories. The craft of "the deal" has led to many a lawsuit, jail time, and high unemployment. What makes any technology company succeed is a dedication to the science and technology behind the product. For this, you need someone outside the royal families. 

Friday, January 10, 2014

The Narrative of Jack Andraka

I would never do a PhD. I’m sorry, but the lab bench is not cut out for me. I don’t want to do academia. I want to work in the clinical field and do business or public advocacy. - Jack Andraka

When I first saw Jack Andraka on 60 Minutes running down the isle to collect his award at the Intel International Science and Engineering Fair 2012, I thought I was watching someone who had just won the Miss America pageant or a chance to bid on The Price Is Right. His demeanor was that of an attention getter. My bias is that I do not like that kind of personality. Rather I gravitate towards Feynman, who did not like awards. I gravitate towards Frederick Sanger who said, "Scientific research is one of the most exciting and rewarding of occupations." I like Einstein who said that true art and science begins where our hopes and dreams leave off. This 16 year old spent 3 months in the lab and a year on the TEDx talk circuit. He was a media darling, but was he a Cargo Cult Scientist?

I've given my bias. I will try to avoid it when making my argument. 

This article from Mathew Herper in Forbes deviates from the positive spin from the popular media that greeted Jacks entry into the scientific community. The title, "Why Biotech Whiz Kid Jack Andraka Is Not On The Forbes 30 Under 30 List".
But I decided not to include Andraka on the list, overriding the recommendation of an expert judging panel, because the work was not yet published in a peer-reviewed scientific journal. It is by published work that scientists are judged.  I still think this was the right decision. In fact, when Andraka volunteered to share a draft of a paper that he does plan to submit to a scientific journal, my concerns deepened.
Here are a few reasons why he is on the Cargo Cult Scientists list:

1) So we really ought to look into theories that don't work, and science that isn't science.

As Mathew Herper points out in his article, Jack Andraka has not yet published his work. Many scientists that reviewed an early version had their doubts about some of the claims. The question science asks, "Does the theory work?" We don't know.

2) Now it behooves me, of course, to tell you what they're missing. But it would be just about as difficult to explain to the South Sea islanders how they have to arrange things so that they get some wealth in their system. It is not something simple like telling them how to improve the shapes of the earphones. But there is one feature I notice that is generally missing in cargo cult science. That is the idea that we all hope you have learned in studying science in school--we never say explicitly what this is, but just hope that you catch on by all the examples of scientific investigation. 

Jack Andraka is a young man with little experience in science. Something is missing in his foray into science.

3) Details that could throw doubt on your interpretation must be given, if you know them. You must do the best you can--if you know anything at all wrong, or possibly wrong--to explain it. If you make a theory, for example, and advertise it, or put it out, then you must also put down all the facts that disagree with it, as well as those that agree with it. 

Mathew Herpers article highlights some critical details that others have had to point out that throw doubt onto Jack and his mentors interpretation of the lab work.

Andraka’s “168 times faster, 26,667 times less expensive, and 400 times more sensitive” figures are based on a comparison with ELISA. But Church saw problems with the way that Andraka characterizes the ELISA test.
Test speed: Andraka says he compared the speed of his test to the amount of time he spent trying to get results from an ELISA kit he ordered online: 14 hours.  But usually a modern ELISA test takes 1 hour.
Test cost: Andraka is comparing the commercial cost for a test – including the manufacturer’s profit and overhead – to his own materials cost. That’s not a fair comparison. He says the only mesothelin test that he found cost $912 per kit. But other ELISA tests are for sale online for $400 per 60 tests or $600 for 96 tests – in other words, about $6.50 per test run. That still compares favorably to Andraka’s $3 per 10 tests, but remember that there would also be a commercial markup if a company decided to sell his tests. 
4) In summary, the idea is to give all of the information to help others to judge the value of your contribution; not just the information that leads to judgement in one particular direction or another. 

Since the work of Jack Andraka has not been published, we need more information. His mentor, the media and the public all want to believe we have a genius in the wings. The stories and awards provide us with the information and judgement in one particular direction. The truth might fall short of this story.

I agree with Mathew Herper, it was a pretty neat thing for a teenager to do. To take an interest in biotechnology and cancer detection at 15 is remarkable. The tenacity to present his idea to a hundred scientist before getting the attention of one is why I think the kid is going places. His science probably won't go nearly as far.

Which leads me to the conclusion that the boy has merely been a pawn in the Cargo Cults of Biotechnology. His mentor did not discourage the boy nearly as much as those meanies who came later. But that is how science must work. The truly talented scientists have a passion for this pursuit. They do what they do because they are good at it. They want to work in a laboratory, design experiments, observe what  happens, and live a life learning new things that no one else has thought of yet. The details that separate science from Cargo Cult Science are subtle, often times the cause of eye rolling among non-scientists. Where some will say, "big deal" a scientist will demonstrate just how big of a deal a seemingly small detail can be. These people are often introverted, soft spoken, and more focused on petri dishes than their own reputation.

As one commenter said from the Forbes article: "Based on your description, the kid sounded pretty promotional. I don’t know if he will become a scientist. I have a feeling he may become one of those slick biotech CEO in a few years."

A scientist is not a CEO of a biotech company, a bureaucrat at the NIH, or a judge of a science fair. A scientist might hold one of these titles, but the titles do not make you a scientist. Each title may require the holder to have a PhD. But science is bigger than titles and awards and the people who strive for them. A scientist is merely a life long student of the natural world that still has a billion secrets left for us to figure out. 

Through art and science in their broadest senses it is possible to make a permanent contribution towards the improvement and enrichment of human life and it is these pursuits that we students are engaged in.Frederick Sanger 

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