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Sunday, September 27, 2015

Risperdal Versus Volkswagen Diesel Engines

What is worse, Volkswagen purposely developing and installing software to cheat on emissions tests or Johnson and Johnson hiding side effects and a lack of efficacy of the drug Risperdal? Let us not focus on the impact of each act of dishonesty. The question is not whether it is worse to pollute the air than to hide harmful side effects of your pharmaceutical (and a lack of efficacy) from the FDA. The question is about the moral behavior of a group of executives. On a scale of 1 to 10, how morally corrupt was the behavior of the Volkswagen and Johnson and Johnson executives?

We often see this situation. A corporation is listed as a defendant in a huge lawsuit. They lose their case, admit no guilt and pay out huge sums of cash to settle. No individuals are held accountable. It is a perfect set up for a criminal organization.

Volkswagen is in the news. Most people know what they did. Volkswagen has admitted their crime. The CEO is gone. Volkswagen is now seriously taking on the job of restoring public faith in the integrity of their brand.

Johnson and Johnson was also in the news. They were found guilty of hiding side effects and a lack of efficacy for their drug Risperdal. They have been fined $2.2 Billion USD... $2.2 Billion?

Volkswagen is facing a potential $18 billion in fines after admitting that they sold 482,000 diesels since 2009. They will also have to recall all the vehicles and modify the emissions systems. And did I mention that the CEO is out of work?

If you divide $18B by $2.2B you get 8.18. Is the Volkswagen scandal 8.18 times as bad as the Risperdal scandal? What about the leadership of Johnson and Johnson and Janssen Pharmaceuticals? Who lost their job? Not one executive felt the need to throw themselves or someone else under the bus like former Volkswagen CEO Martin WInterkorn. These executives still thrive in the pharmaceutical industry. They are what we consider, successful men and women.

It has always seemed strange to me... the things we admire in men, kindness and generosity, openness, honesty, understanding and feeling, are the concomitants of failure in our system. And those traits we detest, sharpness, greed, acquisitiveness, meanness, egotism and self-interest, are the traits of success. And while men admire the quality of the first, they love the produce of the second. - John Steinbeck

Here is a list of drug company fines from 2001 to the present. This is a list on Wikipedia listing the 20 largest settlements from the pharmaceutical industry. Note that the sum total of the 20 largest big pharma settlements with the Dept. of Justice equals $18 billion. The 20 largest fines equal one scandalous act by a car company selling 482,000 cars.

In case you have missed it, The Huffington Post has an ongoing narrative of the Risperdal case entitled Americas Most Admired Lawbreaker by Steven Brill here.

Saturday, September 19, 2015

William Lane Craig - The Gish Gallop

Cargo Cult thinking is embraced by our religion, Christianity. Cargo cults are groups of people who live in a world far separated from western society. Their beliefs have to be judged with consideration of their isolation and history. Christianity in the west does not have such a caveat. In spite of our superior understanding of how things work, we still cling to Jesus and God the same as cargo cult tribesmen cling to John Frum.
Many people in western civilization would not skip a beat if they were born, with the same mental make-up that they currently possess, into a Melanesian body and Melanesian tribe. William Lane Craig is a perfect example.

I first witnessed the madness of this person when watching YouTube videos of Christopher Hitchens. Hitchens is one of my heros. William Lane Craig (WLC) is now one of my anti-heros. He represents the kind of mind that Mark Twain spoke of when he said, "The trouble with the world today is not that people know too little, but that they know so many things that ain't so."

WTC debated Hitchens on the existence of god. Hitchens was brilliant as always. WLC did not belong on the same stage. He would hear an argument, pull out a file in his brain that contained a dumbed down version of the argument and then offer his pre-arranged response. I soon found myself watching WLC videos to pinpoint the thing that was so maddening about him. I listened to his podcasts, watched his debates and I became obsessed. I felt that if I could deconstruct this mans mind I would find a path to cargo cult belief systems.

The first thing I noticed was a curious method of debate. Craig would always choose the biggest words. His arguments were long winded and difficult to address in a public setting. Craig would present several bullet points and his foe would have to address each one to Craigs' satisfaction in order to "win" the debate. Upon failing to satisfy these demands, Craig would take the role of a judge and declare that his foe had lost the debate. In my estimation, WLC was completely destroyed in each debate. The problem was that he was too dumb to know he had been soundly defeated. By reading what others thought about the maddening debate tactics of Craig I discovered the concept of the Gish Gallop technique. If you follow that link to the bottom you will find a link to William Lane Craig. I will leave off of WLC bashing and let the reader learn more about him through the RationalWiki link.

Why does WLC matter? He has mastered the Gish Gallop technique. We must learn from him. WTC will live his life believing what he believes without any resistance from logical arguments. Cargo cults will continue whether or not we go to them and explain where they are going wrong. Science on the other hand must fight against the Gish Gallap form of argument.

The Gish Gallop is the debating technique of drowning an opponent in such a torrent of small arguments that the opponent cannot possibly answer or address each one in real time. More often than not, these myriad arguments are full of half-truths, lies, and straw-man arguments — the only condition is that there be many of them, not that they be particularly compelling on their own. They may be escape hatches or "gotcha" arguments that are specifically designed to be brief, but take a long time to unravel. Thus, galloping is frequently used in timed debates (especially by creationists) to overwhelm one's opponent.

Is the Gish Gallop related to the complicated method of scientific discourse? Is it possible to apply the Gish Gallop concept to scientists who publish hundreds of papers in their careers? In the time allotted for an average human to have a "scientific" career, can we expect Einstein-like discoveries from the majority? Are we sometimes hoping to be believed knowing that our arguments are weak?

In my utopian world of scientific research there is a police force that has no other occupation but to enforce the law. Just as a street thug with thousands of dollars in cash in his pocket gives rise to the suspicion that he has engaged in some form of criminal activity, a scientist who has filled the journals with hundreds of papers should pique the interest of our police force. We must then begin to pour over the many papers with the Gish Gallap concept in mind. Will we find a myriad of half-truths, lies, and straw-man arguments, none of which are compelling on their own? Should we go back and pour over published work as a form of scientific research?

Religion does not like people who deconstruct their history. Stories such as Abraham ready to murder his infant son to somehow please his god do not bode well for the religions who use the story. Besides the immorality of the story, the "fact" that Abraham was 100 years old and his wife Sara was over 90 when Isaac was born presents a real dilemma for the believer. Apologists like WLC are needed to smooth over the bullshit. Science however has an ace up its sleeve. We do not like people like WLC. We like people like Feynman whose minds work differently.

I would rather have questions that can't be answered than answers that can't be questioned.

Sunday, April 19, 2015

Learning How to Fail

I have been taking stock of my 50 years since I left Wichita. How I have existed fills me with horror, for I failed at everything. Spelling, arithmetic, writing, swimming, tennis, golf, dancing, singing, acting, wife, mistress, whore, friend... even cooking. And I do not excuse myself with the usual escape of not trying. I tried with all my heart. - Louis Brooks

I haven't failed. I've just found 1000 ways that don't work. - Thomas Edison

Failing is subjective. The problem with the average judgement of success and failure is that the outcomes are valued more than the effort (the trying). If there was formal instruction on how to conduct research, there would need to be a semester or two on failure. What is it and how do we deal with it? When is it good and when is it bad? How can we write about failure in ways that will be helpful to others?

How can we truly judge an effort (the trying) without the bias that comes from knowing the outcome?

When I was a Boy Scout we had a meeting with about 30 of us boys. The Scout Master told us we were going to have a contest to see who could hold their breath the longest. I took in a deep breath and held my breath for as long as I possibly could, about 50 seconds. The winner clocked in around 4 minutes. This was, of course, a lesson in Boy Scouts never telling lies. When it was over the grown ups had a good laugh. I forget what the joke was, but the Scout Master made his point. No one can hold their breath for that long. In order to achieve the outcome we wanted (winning a prize for being #1) we would have to cheat. The only question the Scout Master needed answered was how long we would cheat.

In my class on coping with perceived research failure, I would start with Feynmans Cargo Cult speech.

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 explicitly say what this is, but just hope that you catch on by all the examples of scientific investigation.

We can't hope that the kids will catch on to the ways of scientific investigation. We can face this dilemna head on. In order to teach lessons on failure we must define what it is. How do we distinguish between a failure, such as using the wrong reagents, versus failing to get the results we expect? How can we teach a student how to look at failure the way Thomas Edison did?

Having worked with Cargo Cults so often I can design several laboratory experiments to test the students in a similar manner to my Boy Scout leader. For example, phage display using New England Biolab kits. See how the students treat the repeat sequences and/or contiminants. Test how the students think about the results. There are papers that have been published that tell us what are the most probable explanations for certain sequences are. Will the students find those papers in their attempts to get to the truth? Will the students make the same mistakes that others have made in their attempts to move the research along to more interesting avenues of creating a narrative.

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.

Wednesday, February 25, 2015

The Narrative

It has always seemed strange to me... the things we admire in men, kindness and generosity, openness, honesty, understanding and feeling, are the concomitants of failure in our system. And those traits we detest, sharpness, greed, acquisitiveness, meanness, egotism and self-interest, are the traits of success. And while men admire the quality of the first, they love the produce of the second. - John Steinbeck

The goal of the politician is to communicate convincingly that s/he operates with the quality of the first to achieve the produce of the second. Science is no different. Our leaders are in powerful positions. They get to tell the story of how they are a part of the productive world of science. How honest are they really?


When you live a life like Frank Sinatra you leave behind plenty of information about who you were. Movies, records, interviews, books, and photographs are there for anyone to tell Franks story. There is one piece film footage that I've seen on two separate documentaries. In the first documentary you see Sinatra surrounded by ten burly men. They are rehearsing for a scene for a movie while Frank was taking a break from recording music in a Capital Records studio. The gist of this scene in the documentary is that Frank is a consumate workaholic. In the next documentary you have the same film footage. It starts just when the rehearsing begins, giving the idea that this is not acting but a moment in his actual life. The scene Frank and friends are going over is one where Frank is playing a tough guy. He calls one of the other men out while the rest stand back in deference to the boss. The gist is that Frank really is a tough guy.

Compare a couple of harmless Sinatra retrospectives to the narrative of a scientists work. In spite of the seemingly objective structure of scientific publications, the fact remains that a publication is merely a narrative. How many hours of work are being represented? How many months? Years? Who did what and how many times did they do it? A carefully edited bit of reality will quickly turn the truth to bullshit. Thus, the narrative is worthy of study as well as the thesis being supported.


1. a story or account of events, experiences, or the like, whether true or fictitious.
2. a book, literary work, etc., containing such a story.
3. the art, technique, or process of narrating, or of telling a story:

What scientists want everyone to believe is that we follow a superior set of rules that guide each and every one of us to a superior understanding of our world. What a study of "the narrative" put forth by scientists might uncover are, as Steinbeck called the concomitants of failure and the traits of our success.

Is it possible that "The Narrative" lies at the heart of our problems? Could a change in how we communicate deliver a blow to the cargo cult careerists among us? Can we design a better way, a solution, to share the experience of our work and what we think it means?

Once again, ladies and gentlemen, Betrayers of the Truth - William Broad and Nicholas Wade

Considered as a literary form, a scientific paper is as stylized as a sonnet; if it fails to obey rigid rules of composition, it will simply not be published. In essence, the rules require that an experiment be reported as if every aspect of the procedure had been performed according to the philosophers' prescriptions. The conventions of scientific reporting require the writer to be totally impersonal, so as to give the appearance of objectivity.

One solution is to replace the peer review system with a system where data and notebooks are actually reviewed by scientists trained in dissecting "The Narrative". This would create a new career path for scientists. Imagine also a private firm that performs due diligence for investors and/or charities. Is it possible to propose such an affront to the status quo of peer reviewed narratives?

Monday, February 23, 2015

Chapter One

The History of the Narrative

A Cargo Cult Tribesman Discusses His Life In Biotechnology

The company was situated in one story strip mall style industrial area in Woodland Hills California. The employee parking lot was stuffed in the center of the buildings. Wind did not stir the air in our secluded parking lot. It was quite. By 5 o'clock it was always empty. I walked to my car at the days end in this uncomfortable place. I hadn't done anything useful today, I thought. My mind seemed to be as empty and quite. No profound thoughts had stirred my brainwaves. It was as though I had been in REM for hours. No matter what I did I couldn't get the technology to work as promised. I couldn't prove that the guys working on selecting drug targets were correct. I couldn't get the RNA interference, the latest big thing in biotechnology, to work as promised. Was it me?

Steve Jobs said that the most important thing is the project. Great things in business are not done by one person, they are done by a team of people. You hire an A Team and you get the job done. You will encounter people who are difficult to manage. They are passionate about what they do. There will be fights. There will be a lot of noise coming out of that conference room from time to time. We all seemed to get along just fine. Some nights however, there was a little noise to be heard in the parking lot. We would occasionally open the loading dock door and have a noon time barbeque. We would have ribs, hamburgers, potato salad, chips, soda... and beer. Lots of beer. The beer drinkers knew the end was certain so they were going to enjoy the final days. I was no prude. I would have a couple beers at lunch but I had a long drive home. I'd go back to work. It made me nervous to think this was even allowed. At five o'clock I'd make that lonely journey out to my car. The BBQ would have degenerated into a wasted day of drinking beer in a sad lonely parking lot. The A team.

When the end finally came, nine months after I started, three years after the company began, it was just as quiet inside as it was out back on a non-drinking day. I entered through the lab. Empty. I checked the front desk. Hmm. No one here yet. I was early as usual. No one in the cubicle area. Finally, someone appeared. It was the Chief Scientific Officer coming out of his office. "Come on in Sal". We were out of money. It was over and he meant today. "Go on home and start your job search. Use me as a reference. You did a good job."

Monday, February 16, 2015

The Cycle and The Betrayers of the Truth

When The Great Recession hit in 2008, Jamie Diamon of JP Morgan said, "My daughter called me from school one day, and said, 'Dad, what's a financial crisis?' And, without trying to be funny, I said, 'This type of thing happens every five to seven years.'"

That was 7 years ago. Are we due for another "this type of thing"? If so, how will the cargo cults of biotech fare after their surge in IPOs?

A cargo cult does not get to experience the arrival of cargo. It doesn't come once every 5 to 7 years. They spend their lives performing ceremonies in hopes of one day enjoying the cargo. Likewise, biotechnology and the pharmaceutical industry employees/scientists can spend their whole careers in hopes of one day working on a successful drug project. It may never come. There are no cycles in real science.

Western investors are just as susceptible to the lure of ceremony as any cargo cult tribesman. They listen to scientists who have the best credentials. They invest in companies that are using the latest Nobel Prize winning "science". They look for companies that need money within a certain range, as opposed to a specific amount for specific tasks. They tend to differ, however, in the attitude towards the lack of cargo. They won't wait a lifetime to see results. Thus, we should be able to predict our that investment cargo cults will begin to pull out of their biotech cargo cult investments.

What makes investment even more risky is the system of conducting science in modern times. It is not as the professional community of scientists would have you believe. We are led to believe that science is a strictly logical process, involving skilled objective scientists performing experiments in the laboratory, that are rigorously verified by other scientists. All work is published and shared in order to advance the basic science. Any deviations from the truth are weeded out in a self-policing manner.

In the 1982 book, "Betrayers of the Truth, Fraud and Deceit in the Halls of Science" by William Broad and Nicholas Wade, a different description of how science is conducted was offered. "Logic, replication, peer review, objectivity - all had been successfully defied the scientific forgers, often for extended periods of time." This book written right around the advent of our modern biotechnology industry, did not think about the influence of a multi-billion dollar industry. It focused only on the problems of science.

Chapters in Betrayers of the Truth include; 1)The Flawed Ideal 2) Deceit in History 3) Rise of the Careerists 4) The Limits of Replication 5) Power of the Elite 6) Self-Deception and Gullibility 7)Myth of Logic 8) Masters and Apprentices 9) Immunity of Scrutiny 10) Retreat Under Pressure 11) The Failure of Objectivity 12)Fraud and the Structure of Science. In 1982 the biopharma world began spending billions and billions of dollars resulting in a handful of millionaires and no significant medical advances. William Broad and Nicholas Wade had sent out a warning. As they explained

Fraud, we believe, offers another route to understanding science. medicine, after all, has derived much useful knowledge about the normal functioning of the body from the study of its pathology. By studying science through its pathology rather than through some preconceived criterion, it is easier to see the process as it is , as distinct from how it ought to be.

The pathology of the life sciences is like a big juicy piece of fruit ready to be picked from the vine. Has anything changed since the publication of Betrayers of the Truth in 1982? Have we taken a few hundred billion dollars and amplified the problems of careerism and non-reproducible work? Clearly fraud continues to be a part of everyday life in the sciences. We are no better at preventing nor spotting deceit. The cargo cult aspects of science and the biotech industry remain steady.

There is a pattern however. The layoffs have begun. Sanofi, InterMune, Abbott, Syngenta AG, GSK, and Amgen all have plans to cut their workforce this year. All signs point towards a rough 2015. The consequences of "Fraud and the Structure of Science" do have a pattern.


In the documentary "I Am" movie director/producer Tom Shadyac asked two questions, "What is wrong with the world and what can we do to fix it?" I have long been asking the same questions about the field in which I am passionate about and in which I once worked. What is wrong is complex. I have spent the last year writing a summary of ideas from this blog that very closely mirror "Betrayers of the Truth". Many of the themes, such as careerism, the structure of peer review and publish or parish, and the simple notion that science is a human endeavor thus subject to constant fraud and deceit, are explored. It is my hope to offer solutions for useful careers in science, not the cycle of the money. I will spend the next year or two or three... editing and self-doubting the effort. Then e-publish and offer my thoughts on this blog.

Sunday, January 18, 2015

Anil Potti vs Bradford Perez

"One day everything will be well, that is our hope. Everything's fine today, that is our illusion" - Voltaire

The Anil Potti saga is not just an isolated case of scientific misconduct. It is a case that follows the known patterns of cargo cult science. The latest news from the Duke University Potti scandal adds a few more details.

Let's first review the patterns of cargo cult science.

Step one: A narrative capable of being published is formulated by a person with above average ambition.

Step two: A skeleton outline of experimental design is set on stone by the ambitious author of the narrative. The design must protect the narrative. Assign a subservient laboratory work force to conduct the experiments.

Step three: The misconduct occurs in the analysis of the data. The author of the narrative aligns the data to the narrative. Any egregious deviations are dealt with by "correcting" the work of the subservient laboratory staff.

Step four: The narrative is written up and submitted to the journals.

In the Anil Potti case:

Step One: Anil Potti, a Principal Investigator at a prominent University, formulates a narrative, popular among the cargo cults. Genetic markers can be identified to help western medical professionals treat disease. Everyone loves a winner, and Anil Potti knew how to convince others that he was a winner. Anil Potti was not the only person with above average ambition. His superiors and most of the people around him supported what he was doing because his narrative was so attractive.

Step Two: Bradford Perez, a third year med student, is assigned to carry out the work that supported Anil Pottis' narrative. He came to the realization that the methods being used to assign patients to clinical trials were not validated. I.E. the methods were more narrative than scientific method. Yet Bradford Perez was in no position to influence the direction of Anil Pottis research/career. As Arthur Caplan, director of the Division of Medical Ethics at the NYU Langone Med Center who is reviewing this case, said, "I have a feeling his lowly status made him someone that they would be able to hope would just go away. There was a little bit of don't-let-the-door-hit-you-on-the-way-out."

Step Three: Perez made several attempts to discuss the methodological issues with Potti. Things do not go well for Perez. He has to make a decision; speak truth to power or join the power in the continuation of the Potti narrative. Validation techniques from the Potti narrative amounted to, "erasing the samples that don't fit the cross validation from the figure and then reporting the cross validation as meaningful and justification for a good predictor".

Step Four: Rather than publishing another paper supporting the Potti narrative, Bradford Perez decides to pursue the courageous path. He writes a 3 page single spaced summary of his concerns with Pottis lab. "I have nothing to gain and much to lose", stated Perez in his letter to the University. He gave up the opportunity to be included as an author on at least 4 manuscripts, a Merit Award for poster proetnation at the ASCO meeting, and a year of med school. He had to put in another year to replace the dishonest research with something in which he could take pride.

The politics of this case are worth studying. Not on a simple blog but at the level of real leadership. As we can see from this case however, the leadership is a large part of the problem. Anil Potti is indeed a Cargo Cult Hall of Famer, but what about everyone else around him? Below and above, many people were spending their scientific careers standing next to the steaming pile of cargo cult science that Anil Potti was putting forth. Why was Bradford Perez the only insider speaking out? Why did his words go unheard by so many for so long?

The rest of us must operate, as Bradford Perez did, against this powerful non-scientific political force. The Cargo Cults are not simple fiefdoms rang by rogue PIs. Rather the Anil Potti story is one of bullying by a powerful person who has no reverence for the scientific method. Political prowess continues to butt heads with the truth. The truth will always win in the long run. But how long is that run and who do we encounter along the way?