Search This Blog

Sunday, January 30, 2011

Oh Pfizer

I've spoke of the truth spectrum. On one end you can miss the truth by making an honest mistake. On the other end you have committed a fraud that you hope to benefit from. In between you can be in a place where you don't care what the truth is as long as it supports your story. That is called BS. Many professional scientists have been exposed as BS artists and gone on to have successful careers. It takes a corporation to be able to get caught at the far end of the spectrum and still survive. It takes money and power to get past violating federal racketeering laws.

Pfizer was ordered to pay $142.1 million to Kaiser Foundation Health Plan and Kaiser Foundation Hospitals for illegally promoting Neurontin for unapproved uses.

Before I go on I must comment on Kaisers responsibility when handing out drugs. Corporate for profit medicine is not a bunch of doctors who get together to discuss what works and what doesn't. They seem to assess symptoms, google them in their brain or some big pharma database and prescribe the magic pill. Problem solved. It reminds one of a scene from Anchorman with Will Ferrell. The main character, Ron Burgandy would read whatever was on the teleprompter. He did not think before he spoke. As a joke someone wrote something for him to say at the end of a broadcast. "I'm Ron Burgandy, that's the news, go fuck yourself San Diego". And that is how the broadcast ended. It wasn't Rons fault. Right?

Kaiser officials alleged they were duped into believing that migraines and bipolar disorder could be treated effectively with Neurontin, approved in 1993 by the U.S. Food and Drug Administration for epilepsy.

They were duped. There is a lot of duping in Cargo Cults. They don't think before they prescribe. It's not their fault.

There are over 300 lawsuits over off label prescribing of Neurontin. It is a dangerous thing according to the lawyers. The scientists and marketing department at Pfizer allegedly knew Neurontin was dangerous also. Where on the truth spectrum does this case really fall. How dangerous is this little pill and what group of people are most vulnerable? Did the scientists, clinical trials professionals, or doctors know that the marketing department was trying to sell the drug to the vulnerable people just for a profit? Did the marketing department really not care about the people they were hurting?

Friday, January 28, 2011

Sinning Against Science

The Sins of Science : A small compilation of people who know how to succeed in the Cargo Cult Airports. It's not as if anyone is ever going to go into the laboratory and check on their results. Right?

The article about scientific scams that you will not find is the one about a team of hard working laboratory professionals who can spot BS and quickly disprove it with empirical data. It is merely assumed that the review process weeds out the liars and cheaters. Why? Because at the highest level they are too sharp to be fooled. This is mandatory for a Cargo Cult. Leadership cannot be questioned. But what do they know of empirical data if they do not venture into the laboratories they rule over?

The word empirical denotes information gained by means of observation, experience, or experiment.[1] Empirical data is data that is produced by an experiment or observation.

A central concept in modern science and the scientific method is that all evidence must be empirical, or empirically based, that is, dependent on evidence or consequences that are observable by the senses. It is usually differentiated from the philosophic usage of empiricism by the use of the adjective empirical or the adverb empirically. The term refers to the use of working hypotheses that are testable using observation or experiment. In this sense of the word, scientific statements are subject to and derived from our experiences or observations.

Those who are charged with deciding if Silvia Bulfone-Paus engaged in scientific misconduct are not the ones who called attention to the BS in her publications. The judge and jury are like her. They left the laboratory long ago and never looked back. Laboratories are for prestige. You raise money for them and put little people in them to obtain results that prove you were correct. But what obligations does the PI have in verifying the results? What do you call second hand empirical data?

The story of N-Rays once again helps us describe modern day science. Long ago, scientists had a way of verifying puzzling results.
Nature magazine was skeptical of Blondlot's claims because laboratories in England and Germany had not been able to replicate the Frenchman's results. Nature sent American physicist Robert W. Wood of Johns Hopkins University to investigate Blondlot's discovery. Wood suspected that N-rays were a delusion. To demonstrate such, he removed the prism from the N-ray detection device, unbeknownst to Blondlot or his assistant. Without the prism, the machine couldn't work. Yet, when Blondlot's assistant conducted the next experiment he found N-rays. Wood then tried to surreptitiously replace the prism but the assistant saw him and thought he was removing the prism. The next time he tried the experiment, the assistant swore he could not see any N-rays. But he should have, since the equipment was in full working order.

What can one say about N-Rays and the multitude of scientists who publish papers on things they've never seen first hand? Self deception is one explanation. On the other end of the BS spectrum you find Dr. William Summerlin who coloured in the black patches of fur on white mice with permanent markers to prove his skin graft technique was a success. Bulfone-Paus' people coloured protein bands on western blots. Either way, they got what they wanted. By separating yourself from the collection of empirical evidence you will have an easier time climbing the ladder of successful scientists in todays world. By not entering that lab you will not have to fabricate data. You hire people to do that for you.

Monday, January 24, 2011

Questioning Favorable Results

Baltimore, Bulfone-Paus, and Daniel Klessig all had the wool pulled over their eyes by people telling them what they wanted to hear. It is not only easy to do this to some scientists, it seems to be the only way to get ahead in their world.

It's not always black and white. Baltimore wanted the data from Imanishi-Kari. Imanishi-Kari got the data from her lab staff. The data that was wanted was published. The data that contradicted the desired results was the cause of a whole lot of trouble.

Bulfone-Paus wanted the data from subordinates who worked in her laboratory. She got it and published. When did she decide that there was a problem?

Daniel Klessig wanted the data and he published. Trouble!

How does the Cult deal with the trouble?

Highest level:

A BTI investigation concluded there "was no conclusive evidence that Dr Chandok achieved the results reported" but also found "no conclusive evidence" that misconduct had occurred.

Publishing data that no conclusive evidence supports isn't scientific misconduct?

Principle Scientist Leadership level:

This was considered a significant discovery in the field of plant biology. Dr. Klessig and Dr. Chandok began work on a paper to publish the results. Dr. Klessig requested that Prof. Brian Crane, a researcher of animal NOS activity who was familiar to Dr. Klessig, attempt to confirm.

And it was confirmed! How?

Prof. Crane assigned the work to Mr. Pant, a doctoral student who was already performing similar work. Dr. Chandok worked with Mr. Pant to reproduce the results, which was reported as a success. At that time, Dr. Klessig seemed satisfied with this verification, and the paper he and Dr. Chandok completed was submitted to Cell for publication. The paper was published in the Spring of 2003.

Remember the degrees of separation? The fact that PHd scientists do not work in laboratories to confirm data? Dr. Klessig needed to keep building on this foundation of quick sand. He needed more proof. To the lab?

In 2003, Dr. Kim was hired and assigned to verify Dr. Chandok's work.

Were they not convinced yet? What was wrong? Whatever it was, Dr. Chandok wasn't about to go back into that damned laboratory to validate her work. Dr. Kim was not getting the same results as she did. She sued over the retractions of the papers.

Was it scientific misconduct? Bad science? Fraud? Error?

It was a Cargo Cult Science!

Wednesday, January 19, 2011

The Culture of the Cult

Western blot and ELISA are simple things. They are also what got David Baltimore and Silvia Bulfone-Paus into trouble. Both tests can give varying and ambiguous results. When you are on the margin of detecting a signal that proves your theory, you should bend over backwards to prove you did or didn't detect it. This, however, is a part of the culture of the cult.

As a cargo cult leader, you must set up what you perceive to be the truth. The bamboo antennas for example, may be reshaped time and time again. Each time you must have a reason for reshaping the antennas and a reason for the new shape. Therefore, there must be some truth that makes the old shape wrong and the new shape correct. That truth is the heart of the matter. If the makers of the antennas screw up, you can maintain, as a leader, that you are still the keeper of the truth. You are in charge and the others need to do their job better. In general, you must keep several degrees of separation between your "heart of the matter" and the incompetence of the others. They keep the planes from landing in spite of your brilliance.

How does this translate in the real world of science? You may think that scientists work in laboratories and maintain careful records of all they do. This is false. I once worked for a Nobel Prize winning scientist. He came into the lab once to have his picture taken for the award ceremony. He was loaned a white lab coat. He posed next to a hood where inside we had lit a bunson burner for a special "sciency" effect. Later that photograph was hung up inside the laboratory. The caption underneath the picture read, "this isn't like my piano at home". Rest assured, this would have made the Nobel Prize winning scientist very angry. There was little chance of him ever seeing it however. It was inside the lab.

It is not just Nobel Prize winning scientists who stay away from the plebeian confines of the laboratory. Almost all PHds stay away. The laboratory worker is the lowest member of any scientific project. Ironic? There are scientists, project managers, department heads and many more individuals, all of whom help create the degrees of separation. This is why Dr. Silvia Bulfone-Paus had the wool pulled over her eyes by her scientific misconductors. 12 papers now have to be retracted which will effect the other non-laboratory scientists. Their lab staff may have already tried to replicate the results that were a part of the misconduct. At this point it becomes a toss up between who is right, your lab tech or the published (un-retracted) paper. It's hard to use laboratory data to refute published data. Non-laboratory scientists prefer published data.

The quest for fame and funding create this culture. That is what this Cargo Cult Scientist believes. Toiling away in the lab for days only to find out your protein was misfolded or your reagents were at the wrong pH in step 27 is tough. It's also boring. You end up in an office with the non-laboratory scientists explaining what happened. If it is what they wanted to happen you will have an easy time. If it's not the mood turns dark and the relationship becomes more adversarial. But reality is best observed in the laboratory. That is where we need to go back to. Considering how much money has been lost in the industry, can we afford to keep the degrees of separation in place?

Tuesday, January 18, 2011


Once again we see an old pattern. A scientist wants the world to work the way they think it does. They've done all the right things and they are in a position to help write/rewrite the texts books used in Universities throughout the world. They must be scientists! So it is time to get to work and publish everything you can that supports your career. There may not be time to follow Feynmans recommendation:
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 journal Nature seems to be against this idea.
An unknown agitator using the presumed pseudonym Marco Berns is engaged in an e-mail and Internet offensive against two biomedical researchers whom he accuses of scientific fraud.

It seems as though they (Nature) are against "blinding". This agitators greatest crime is his/her anonymity. What do we know about the people who wrote this article in Nature? They represent authority just like Silvia Bulfone-Paus in her role as a principle investigator. What really matters? Are we religiously placing faith in Nature editors and tenured professors? Perhaps anonymity is a scientific imperative. There needs to be a "blinding" of the judges and those presenting the case. Then take a different angle at looking at the problem. That is what we do in clinical trials. That is what we do in the laboratory with our "controls". The content of the claims is what needs to be analyzed. Rather than addressing the issues, Nature has chosen to attack an unknown person for going about things the wrong way. But what are the chances of getting Nature or the Research Center Borstel to explain to the rest of us how they came to their conclusions? Is it not a pattern for these organizations to protect the scientists and attack their detractors through anonymous reasoning? Just trust them because they are in charge?

What you don't hear about in many articles about the Silvia Bulfone-Paus story is what exactly her "agitator" is saying. It is interesting stuff. This is the stuff you want to know if you are honestly doing what Feynman suggests. I'm not talking about IL15 and the papers that need to be retracted. I'm talking about whether or not Silvia was not at fault. The data that was fabricated supported her story. She didn't look into it nor did anyone else try to repeat a simple western blot. The false data fit her story and she stuck with it. It's a crime against the good name of science.

Wednesday, January 12, 2011

Why Sequence Your Genome?

As one reporter puts it, "it’s worth remembering that it took $3 billion and about 13 years just to sequence one genome, and as of a couple years ago, it was so expensive and time-consuming, only about a dozen or so complete genomes were sequenced. Today, a company tells the world it will sequence 615 complete genomes for a single customer, and Wall Street gives it a paltry 5 percent stock lift".

The problem with sequencing your genome is this. You can take your car apart and lay out each part in a line. Maybe photograph each part and catalog it in a book. What does it mean? You still don't know how your car operated. Now imagine a new company trying to sell you a technology that makes the dismantling and cataloging of the parts 10 times faster. So what?

They need to put some wealth into their system.

I had a professor tell the class that most of the DNA in our genome is junk. It didn't do anything. He was referring to the fact that genes make proteins and that is doing something. The rest is doing nothing. Arrogance! When certain environmental changes occur a stem cell will decide to become a specific kind of cell. How does the linear sequence of nucleotides change? Perhaps not at all but certain genes will cease to "do something" while others will begin to "do something".

Of course there are many many scientists who are working to explain what DNA does. Geospiza for example, is a company that makes software for biologists to analyze genomic data. Biologists are taught to know what DNA is. They know about the nucleotides and the phosphate backbone and so on. But what do they know about translating a DNA sequence into an explanation of life? I guess that's what the software is suppose to help them do. That is the most interesting aspect of genome sequencing. If only there was a translator to accompany the sequencer! I don't believe one exists. Indeed, the field of Genetics is full of cargo cult scientists.

So where is the profit in the new superfast DNA sequencers? Those with the money and an almost religious faith in "science" will have their genomes sequenced and rely on their doctors to tell them if they are at risk for certain diseases. For example, the ApoE-ε4 gene isoform is tied to an increased vulnerability to Alzheimer's. There is nothing you can do about it but some people want to know what to expect. Probably not enough however to turn a profit. One would think that the rapid sequencer companies would have a genetics branch in R&D to explain what your sequence means. Imagine your future is written in book form in Spanish. Wouldn't you hope for at least a translator to tell you what the book says? The sequencer companies have a business model for half a product. They are too blinded by how neat the first half is.

What if the Genetics scientists were the real customers for the sequencing machines? Sequence one persons DNA every month for his/her life. How does it change? What do the changes mean? What if you had identical twins and one smoked and the other did not? What happens to the linear sequence of nucleotides on a genome then?

We have to build wealth into this system. It can be done. It is very interesting for reasons no one is talking about. It's not sexy and it's not going to result in a Nobel Prize for a young scientist anytime soon. Rather this kind of research should be done by a group who toils for the lifetime of the subjects being tested. After we all die the next group of scientists will still have to try and make sense of the variations. The telomeres fade away. We see anuploidy in cancer cells. Point mutations, silent mutations, hairpin loops and on and on. How does any of this happen and what does it mean?

Saturday, January 08, 2011

What Works

Biogen Idec runs in the black. It generated $4.37 billion in revenue in 2009, and has a workforce with 4,275 employees at last count. The R&D budget was about $1.3 billion in 2009.

Despite all that, Biogen hasn’t been able to deliver a new FDA approved product since natalizumab (Tysabri) in 2004. The lack of R&D output has prompted blistering critiques from billionaire investor Carl Icahn, who accused the company in 2009 of suffering from “failed leadership.”

Last year was the first time in a decade that Pfizer Inc., the world’s largest drugmaker, as well as Merck, Eli Lilly & Co. and Bristol-Myers Squibb Co., each failed to win regulatory backing for a new molecular compound.

The airplanes did not come!

Leadership? Finance experts telling scientists how to do their job? Businessmen who run companies have all the answers as to why scientists in their organizations aren't producing. But what about this?

Brain plaques, long considered the chief killer of brain cells and the cause of Alzheimer's disease, may actually play a protective role under a new theory that is changing the way researchers think about the disease.

Imagine that. Scientists have been trying to treat a disease by possibly attacking a protective response by the body.

Scientists in biotech succeed all the time. For example, if you have an protein drug, scientists successfully identify cleavage products that are considered impurities. Next the scientists successfully remove those impurities. Science, when properly applied, gets the job done.

What have drug companies mentioned above been missing? Perhaps they could hire a team of scientists to look into what targets are taking them down the wrong road. The "experts" have lead the drug manufacturers into the state they are currently in. Perhaps a new biotechnology could one day arise that sells unbiased assessments of the path they are currently on. No Yes Men!

Friday, January 07, 2011

Merck Logic

Merck has a plan. The new Chief Executive Officer Kenneth Frazier said the company will make “tough” research spending decisions while developing innovative products.

Merck hosts regular symposia where its finance experts teach scientists how to seek better return on invested capital, Frazier said. The three-year return is now tied to researchers’ compensation, he said.

Finance experts? Teaching scientists? We at the CCS are of the belief that no one who works in finance holds half the expertise in their field as the average mechanic holds in theirs. We clearly do not believe that a scientist can be taught anything. Their arrogance prohibits them from being on the learning side of the any educational scenario.

I guess we all want to be the expert/teacher. Those running Cargo Cult Airports teach their underlings how to run the Cult. The underlings (middle management) hire the people who run the airport. Upper management then lives and dies on the Cargo. How far gone must Merck be to have finance employees telling scientists how to get the most out of their R&D budgets?

Why is this story not scorned by the entire world, let alone some lone voice that can be heard? My voice is not heard. No one is going to say, "the CCS makes a valid point, Merck has tied finance to science and that just doesn't make any sense". But if you are like me, you get in your time machine and you go back and listen to all of the intelligent talk about how Merck and Pfizer and all the rest were going to turn things around and start getting drugs approved. Then you come back to the present and you see how they did.

I leave you now to hop into that time machine. I will travel three years down the road to see the how this plan worked out.

Sunday, January 02, 2011

Writing About Work

In order to build "wealth into our system" we have to learn how to write. In school we are taught how the English language is to be used properly. Grammatical errors in any course your take may just lower your score. You could use a double negative on an essay question in history class and you lose points. Proper English is always important. What is just as important in science is knowing what needs to be documented.

That may just show my own bias towards certain people I've worked with. The worst of the worst rarely put anything in writing. When they do you almost always have to ask for clarification. The best of the best always try to get what matters written down. Yet even in college the laboratory notebook is taken for granted. It's another thing that is graded. Mistakes are quantitated. The more you make the worse your grade. However, the biggest mistake is to not say anything about something that people are going to want to know. Most often you are going be that person.

The FDA, your scientific misconduct investigators, your PI, your boss are also groups of people who are going to want to know what you do in the laboratory. Most likely you're going to be in trouble if these guys come snooping into your notebook. They are going to grade your notebook. The Baltimore Case gives us keen insight into how this works. A postdoctoral fellow in Imanishi-Kari's laboratory, Margot O'Toole, could not reproduce the results from an experiment that was discussed in a paper published in Cell. Once an office bound scientist publishes something, they protect their claims in a most unscientific way. They did not compare notes taken by two different people who performed the work in the lab. They took what suited their story best and stuck with it using their authority to silence the confounding evidence. But Margot had her data. She used it to make her case. A personal conflict between the two scientists developed. Margot O'Toole bravely went forth with her laboratory notebook to back up her story. What happened next was non-science and Imanishi-Kari and Baltimore got away with their misconduct. Margot O'Toole spent the next few years working out of science as a result.

This would appear to indicate that Margot O'Toole did not have compelling evidence written in her notebooks. It was however alleged that Imanishi-Kari was the one who had not been adept at keeping notes on her work.
"I was supposedly wasting materials by doing the experiment and coming up with the wrong answers." Shortly thereafter she was demoted to breeding lab mice. Then, in the course of researching the heredity of one particular mouse, O'Toole consulted lab notebooks used by Imanishi-Kari and made an astonishing discovery: The data recorded there didn't support Imanishi-Kari's conclusions either. "I knew [the conclusions] had been fudged," says O'Toole. "Finally the world made sense again to me."

Writing down what you do is a skill. You don't always realize something is important when it is happening. Imanishi-Kari didn't realize that there was evidence left behind that what happened with O'Toole was the expected outcome. The laboratory notebook had the real story. The journal Cell, was lied to. This leads to a very important piece to what Feynman was talking about when he spoke of building wealth into a system of discovery. The things you observe and take note of can lead to the truth. Even if you write down that you looked up at the moon last week and it wasn't there, you have useful information. The moon was there but we had an eclipse. You just didn't know about the eclipse. Not seeing the moon (okay I know you can still see it) doesn't mean the moon failed to exist. So just be honest and you will be rewarded. Do what Baltimore and Imanishi-Kari do and you will probably get published more often, but you will not get the rewards that scientific people care about.

Celebrex is an example of how the Pharmaceutical industry doesn't get this. Pfizer had clinical trial data that showed how the use of this pill increased the likelihood of heart attack and stroke. The FDA doesn't require the drug companies to disclose information on every trial so they do not actually have the ability to protect us. They hear what the drug companies chose to tell them.

In summary, the idea is to try to give all of the information to
help others to judge the value of your contribution; not just the
information that leads to judgment in one particular direction or

Keep good records, even when you don't know what they mean. It will come to you later when you have more information.