Search This Blog

Loading...

Monday, February 08, 2016

Thronanos Seeks Bullshit Artist

RESPONSIBILITIES
Innovate and conceptually solve problems through the power of excellent storytelling.
Integrate narratives utilizing film, books, television, retail and emerging web entertainment.
Collaborate with the creative team on most projects.
REQUIREMENTS
Bachelor's Degree from a top tier university with solid journalistic/creative/marketing credentials.
3+ years of experience as junior copywriter/screenwriter in a creative environment advertising agency, studio, freelance writer, graphic design firm, etc. with experience working on narrative driven projects, both professionally and personally.
Strong knowledge of Microsoft word.
Demonstrate a high level of initiative and ability to function superbly in both individual and team environments.
Handle stressful situations and deadline pressures well.
Team-oriented and collaborative idea building skills are a must.
Bold experimentation in different styles of writing and communications are a must.

The book I am writing is tentatively titled, "The History of the Narrative". When I thought about the biggest difficulties facing real science and the cargo cult mentality within biopharma, it always came down to "the best story". As former Amgen scientist C. Glen Begley discovered:

Part way through his project to reproduce promising studies, Begley met for breakfast at a cancer conference with the lead scientist of one of the problematic studies.

"We went through the paper line by line, figure by figure," said Begley. "I explained that we re-did their experiment 50 times and never got their result. He said they'd done it six times and got this result once, but put it in the paper because it made the best story. It's very disillusioning."

Such selective publication is just one reason the scientific literature is peppered with incorrect results. -Sharon Begley, Reuters

The narrative of the cargo cults of biopharma always seeks the best story. Contrast this with real science being restricted to only telling true stories. This job description from Theranos is either an example of the cargo cult "best story" problem or just a poorly worded ad for a marketing specialist.

The danger to the rest of us is the fact that Theranos is selling itself as a tool of the healthcare industry. The narrative they are putting forth can be found in their mission statement, "Our mission is to make actionable information accessible to everyone at the time it matters. By making actionable information accessible to everyone in the world at the time it matters most, we are working to facilitate the early detection and prevention of disease, and empower people everywhere to live their best possible lives." If there is any creativity from a top tier University B.Sc. found in the actionable information concerning the detection and prevention of disease, then we have a problem. Hopefully the writer would only be used to help spin the story about Theranos and their many scandals.

A very simple test on the Theranos product was shown here. Such a random sampling is so simple. In this piece Jean-Louis Gassée, a former director of engineering at Apple who is "compulsively curious" compared the Theranos narrative to reality. Using an alternative blood testing service Jean-Louis came up with some data. He contacted Theranos with his findings and received no response.

For a $9+ billion company that has the federal government on its board of directors, the hiring of an undergrad as a spin doctor seems crazy. Where in the massive dung heap of BS does the new guy enter? How many "creative storytellers" within Theranos have been brought in before him/her? What did their job description look like?

Tuesday, February 02, 2016

Harlan Krumholz On Data Sharing

It is easy to envision how a community of scholars should be organized. Every idea would be taken on its merits, and every person judged on the worth of his ideas. The need for a social hierarchy would be strictly limited. Each member of the community would enjoy status that was determined by merit and that owed nothing to social standing or any other personal attribute. Elite group[s might appear temporarily but would never outlast the original reason for their existence. -Betrayers of the Truth, Chapter 8, Power of thew Elite -William Broad and Nicholas Wade

In a world where social hierarchy is strictly limited, why would a scientist withhold data? To gain notoriety a scientist must get his/her work published. That means communicating with the rest of the community. Communication is the purvey of the bullshit artist. Scientists write up their papers according to the structure required. Somehow the required structure of the scientific paper has evolved to excise meaningful data. One possible explanation is that those who are now in charge were once up and coming researchers. They knew the perils of data sharing to their careers. Now, as leaders, they have opened up the path to more creative narratives. Science took the hit and careerists had way around the old fashioned rigors of science.

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. 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.

Scientific integrity, the layman might assume, means operating in the ideal world described above. The world where ideas are judged on their merits and not by the pedigree of the originator. Scientific integrity, the layman might assume, means that the leaders of the scientific community require their underlings to report everything, good and bad. Yet the scientific paper has evolved to the point where the actual data that supports the conclusions is top secret. And the rest of us do not have the proper clearance.

AllTrials is an organization that sees the problem and seeks to do something about it. AllTrials has targeted the pharmaceutical industry and their clinical trial data. Another scientist pursuing data transparency is Harlan Krumholz. Please read his article and listen to the NPR interview.

Data sharing is knowledge sharing. It is the same concept of forming a university where we share knowledge with intelligent young people in hopes that they will further the knowledge. Dr. Krumholz says
Among the first things we learn in school are to share and to show our work. This lesson has been lost on medicine for many years. The medical editors are reminding us that we scientists have a principal responsibility to society and to those who agreed to participate in our studies.


Sunday, January 24, 2016

C Glen Begley Demonstrates the Perils of a Biopharma Career

C Glen Begley, author of The Amgen Study, is out of work again.

After the company terminates the 19 employees it plans to, TetraLogic will be left with 10 employees, the Journal said. Among those terminated are G. Glenn Begley, the company’s chief scientific officer, and Lesley Russell, the company’s chief operating officer. Their termination will occur on April 19, the Journal reported.

When Begley and Ellis wrote their paper on the difficulties of using bad science as a foundation for ones research they were acknowledging that there was a problem. Not everything we read in the journals is true. Some say most of it is not true. If you work in the biopharma industry you know that job of yours is contingent upon the success of the molecule on which you are working. If it does not perform according to the narrative of the company, you might be tossed out the door along with the project. Even if your job is to simply clone, grow, purify, define biochemically the molecule, you will be packing up your belongings from your cubicle if the molecule does not succeed in the clinical trials.

TetraLogic had a plan. Birinapant was to be a treatment for high-risk patients with myelodysplastic syndromes. However, phase II trial results showed birinapant did not demonstrate any clinical benefit over placebo. The study has been terminated, and C Glen Begleys job has been terminated. So has 18 other individuals including the COO/CMO! Was that a part of their plan? Were the leaders upfront about the connection between everyones job and the outcome of the phase II trials of birinapant?

Of course the CSO and CO/MO are a part of the leadership. They make the decisions and serve as spokesmen/women for the narratives of the company. Scientifically they had to have reason to believe that birinipant would succeed but I doubt they were betting their jobs on it.

Birinapant is designed to mimic the activity of an endogenous protein, the Second Mitochondrial Activator of Caspases, or SMAC, which is involved in the regulation of the apoptotic process within cells. Avoidance of apoptosis is a critical step in cancer tumor development and certain infectious diseases. Birinapant reactivates one of the common apoptotic pathways, thus restoring the natural balance in our bodies. This is a completely novel approach to treating these diseases and may provide new treatment options for patients suffering from cancer or serious infectious disease. The company is reviewing its strategic alternatives in light of the birinapant clinical trial results announced on January 6, 2016.

To add a little more detail to the scientific knowledge of SMAC for us laymen:

Myelodysplastic syndromes are a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. In patients diagnosed with myelodysplastic syndrome, the “blood stem cells (immature cells) do not become mature red blood cells, white blood cells, or platelets in the bone marrow. These immature blood cells, called blasts, do not work the way they should and either die in the bone marrow or soon after they go into the blood. This leaves less room for healthy white blood cells, red blood cells, and platelets to form in the bone marrow. When there are fewer healthy blood cells, infection, anemia, or easy bleeding may occur,” according to a report on cancer.gov.

So birinapant was suppose to fine tune apoptosis of blasts which would make proper room for healthy white/red blood cells and platelets to form in the bone marrow. That was the narrative. Once the fine tuning was accomplished by birinapant the disease state would no longer bedevil the patient. It worked as well as, but no better than a placebo.

The cynefin method of thinking would have helped the people who lost their jobs.



All biopharma research projects have a narrative that states molecule X will cure or treat disease Y. Biotechnology works. It operates in the known knowns area after the known unknowns are dealt with. Does birinapant properly mimic SMAC. That was a science/technology project that succeeded and that is the job of the scientific staff at TetraLogic. Then came the unknown unknown. Will birinapant go into the body, find its way to where SMAC was lacking and properly restore the function of the endogenous protein? When the narrative went from known unknown (SMAC is lacking and birinapant will fix the problem) to unknown unknown (will birinapant solve the problem?) and then to known unknown (birinipant will not fix the problem of SMAC deficiency) the project was deemed a failure and jobs were shed.

That is how it works. Even an honest man such as C Glen Begley is not immune to this dilemma. Everyone working in science must admit that they are not going to get it right every time. The most perilous place to be is on the scientific frontline when the results come in.

Sunday, January 03, 2016

Hillary Clinton Cures Alzheimers

Hillary Clinton has announced a nine year plan to cure Alzheimers. Not a bad idea. What about the plan of action? I want to examine her plan from the perspective of Design of experiment . You won't get the perfect method using the statistical method of design of experiment. You will get the best possible method within the time and materials set forth.

Experimental design involves not only the selection of suitable predictors and outcomes, but planning the delivery of the experiment under statistically optimal conditions given the constraints of available resources. -Wikipedia

According to the Alzheimer’s Association "nearly all we know about Alzheimer’s, we have learned within the last 15 years, due in large part to significant federal investments in research". $2 billion per year for the next nine years will finish what was started. Why that amount? The research advisory council to the congressionally backed National Plan to Address Alzheimer's Disease have said $2 billion a year could make a cure possible by 2025.

The bullet points of the plan:

1) Commit to preventing, effectively treating and making a cure possible for Alzheimer’s by 2025.
2) Dedicate a historic decade-long investment of $2 billion per year for Alzheimer’s research and related disorders.
3) Ensure a reliable stream of funding between now and 2025.
4) Establish a plan of action with NIH, leading researchers, and other stakeholders to see the 2025 goal through.

Who are the players in this plan? If we look into the details of the bullet points we get:

Top researchers have noted that this is achievable if we make the commitment, marshal the resources, and provide the needed leadership.

$2 billion annually, the level leading researchers have determined is needed to prevent and effectively treat Alzheimer’s and make a cure possible by 2025.

Clinton will appoint a top-flight team to oversee this initiative and consult regularly with researchers to ensure progress toward achieving the treatment target.

These top researchers providing leadership will guide the spending of $2 billion per year. Ultimately Hillary Clinton is the leader but her top flight team will oversee this initiative.

The 2014 National Plan to Address Alzheimers Disease omits "making a cure possible" by 2025. The goal they had set forth was only to prevent and effectively treat Alzheimers Disease by 2025. Hillary, being the master politician said I will get you the money but we will add the wording, "making a cure possible".

One can assume that a cure is already possible because the disease exists. The question is the probability of finding a cure. Does this plan increase the probability to the point of certainty by 2025? The wording here is very cargo cult. Will the cure by delivered from the belly of the big metal birds that come from the sky? Will the belly open up and spill out large boxes filled with syringes of medicine that stop the elderly from losing their minds? According to our leaders, nine years and $18 billion down the road... sure it's possible to get that cargo.

Something is missing. Feynman said:

This long history of learning how not to fool ourselves — of having utter scientific integrity — is, I’m sorry to say, something that we haven’t specifically included in any particular course that I know of. We just hope you’ve caught on by osmosis.

That same "something we haven't specifically included in any particular course" is also missing from Hillarys' plan. The most troubling aspect of the plan however involves the end of the Cargo Cult speach.

I
have just one wish for you — the good luck to be somewhere where you are free to maintain the kind of integrity I have described, and where you do not feel forced by a need to maintain your position in the organization, or financial support, or so on, to lose your integrity. May you have that freedom.

You cannot have that freedom when you have to answer to Hillary and/or her "top flight team". When you have nine years to cure Alzheimers so Hillary can check that off of her legacy list, you will have to spend considerable energy maintaining your position in her organization. If you fail to convince the politicians of progress your funding will go to the golden child down the road.

To pinpoint that thing that is not specifically included in Caltech science courses let us turn to the classic "Betrayers of the Truth" by William Broad and Nicholas Wade.

Chapter 7, The Myth of Logic - Science is the distinctive enterprise of Western civilization in the twentieth century, and yet it is perhaps the least well understood. A major reason for this gap is that the philosophers of science, who have influenced the general conception of how science works, describe it as a purely logical process.

There is indeed a logical structure to the body of scientific knowledge, but the logic is often easier to see in retrospect, after the knowledge has been gathered. The way in which scientific knowledge is produced and disseminated is a wholly different matter. It is an activity in which nonrational elements such as creativity or personal ambition play conspicuous roles. Logical thought is of course a vital element in scientific discovery, maybe even more so than it is in poetry, art, or any other high exercise of intellect. But it is not the only element.

Certainly, Hillarys' plan has the ambition. But it also assumes that the research of the past 15 years has put us on a nine year path to curing Alzheimers. I can just hear the argument now, "We never said we would have a cure! We said we'd make a cure possible. That's different! In the year 2015 will we see the logic in retrospect the same as we see the logic in todays plan? What in the plan provides for learning how scientists and politicians can work together to cure disease? If Hillary and her top flight team can cure Alzheimer's then we need them to create the Design of Experiment method for all future scientist/politician teams. For they will not only have solved a problem that has plagued humanity since the dawn of time, they will have found a method of solving problems.

In closing I will conclude that this is bad for science. What is needed is experienced scientists. We need the kind of people who will not attract the likes of Hillary Clinton. We need the people who will shoot down the popular sexy ideas that make headlines but lead us astray. We need scientists who understand that we can only follow the path. We can't decide where it is leading based on what we want. We only have the method of following one truth to the next truth. False claims can take years to correct. If we want to cure any disease we must find ourselves where we are free to maintain our integrity. Where we don't feel forced by a need to maintain our position in the organization, or financial support. The nine years plan to cure Alzheimers does not understand what is needed to properly conduct science.

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.