Born Sick, Commanded to Be Well

A cargo cult is an example of how any religion gets started. People see the complexity of the world and they can't accept not knowing how it works. They need answers. Faced with their ignorance they quickly seek anything that they can understand. Gods have always fit the bill. They created the world in which we live. Don't ask any more questions, just worship.

The actual cargo cults want to believe that someday they will have big metal birds delivering their food and medicine. Rather than focus on obtaining these things via the scientific method they take an easier route. To rectify the situation would be simple, at least in the beginning. Talk to the westerners and ask them how they built the airports. Learn that building your own airport is possible, but it is going to take hard work. They have to move from the simple belief system of religion to the complicated understandings of science and technology and progress at understanding the complexity of life on earth.

This clip of Bill Burr letting go of religion demonstrates a couple elements of the biotech cargo cult science. We often hear from the leaders that they cannot find the right people. The people they have to choose from are the ones the industry has educated and trained. They created us and now they want us to have a different skill set! Once again let me pick on Juno Therapeutics.

Hans Bishop, chief executive officer of Juno, said the state (Washington) needs to provide incentives to biotech companies in order to spur growth from existing companies and to attract small and mid-sized biotech companies to the region. Bishop said the state’s talent pool needs to be built up, which will happen through fostering innovation. He said Juno has had to attract more than half of its 300 employees from out of state.

Juno Therapeutics began when Lawrence Corey met David Fallace on a flight from Boston to Seattle. Fallace was in charge of special opportunities for the Alaska Permanent Fund. Ironic that a fund that wishes to be permanent would invest in biotech start-ups. Larry Corey was running the Fred Hutchinson Cancer Research Center. The two formed a partnership that got Juno off the ground.

Larry Corey. He once worked with Gertrude Elion, whom we at the CCS love and admire. At a presentation I attended in Colorado she ended with a slide that had a picture of the path she took in research. It went from chemistry to microbiology to biochemistry to medicine and so on. She was asked by a biochem professor how that path would have been altered if she had had the new technologies that we currently have. She said that it would not have mattered. The real work was done by thinking of the scientific problems and not the human constructs of technology. I'm paraphrasing but I believe her point was that research is a journey that takes you places. If you begin with technology and force it to take you to the land of milk and honey you will never get there. Larry Corey, on the other hand, took what Gertrude Elion had begun and headed off to the cargo cults. His career is in leadership, power, and money. In 1987 Corey directed the AIDS Clinical Trials Group, or ACTG, which conducted pivotal clinical trials confirming the use of the antiretroviral drug AZT to reduce maternal-fetal transmission of HIV and the usefulness of highly active antiretroviral therapy (HAART). Horrible research done without a heart and soul. He has authored 12 books and more than 690 scientific publications. Quantity over quality is a cargo cult career skill. Larry Corey has had one hell of a successful career in the cargo cults.

The "permanent fund" that invested in Juno no longer has Fallace and Corey to develop their idea. They have both moved on to other things. One has to wonder why anyone would leave such a promising narrative? Leadership in the cargo cults however requires one to keep moving. You don't want to be around when the followers look up to the skies to see once again that the planes will not be coming. The new leaders of Juno have already laid the foundation for failure. The state of Washington is somehow obstructing their ability to attract the right talent. "Washington state's talent pool needs to be built up, which will happen through fostering innovation." Has Corey innovated? The problems he set out to solve are now being left to people who must emerge from a talent pool that has not yet been built by our leaders. They need government money first!

The talent pool that currently exists in Seattle consists of ex-employees of the cargo cult companies that have come and gone. Resumes of people in Seattle life sciences include the companies that leave many an investor with a bad taste. Bad science is not sustainable nor is a talent pool that comes from such companies. The people naturally change their ideas on how to maintain employment. Like Lawrence Corey, they seek to distance themselves from the situation that makes science fun. That moment you go into the lab in the morning to see how your experiment turned out. The anticipation that your work is leading to bigger and better things. The confidence of mastering skills that once took so much of your time. The talent pool that innovates does not exist in Seattle. But unlike Bill Burr letting his religion go, it is the cargo cults that let their people go. The narrative lives on even though there is no talent to validate.

The problems facing life in the life sciences is daunting. Those who wish to have a career discovering new biotechnologies and helping mankind will soon run up against the need for survival. The likes of Lawrence Corey will be your competition. He, along with the other leaders of Seattle life sciences, have created a talent pool that is not good enough for their latest narratives. My advice to the young scientists is to stay away from biopharma, medical science and the gurus who start companies who seek massive profit. Develop technology, not drugs. Let go of the religion of western medicine. Biotechnology does not have to be synonymous with pharmaceuticals.

The Money - Shkreli to Juno

Forbes had an article in their February issue called "Solving Pharma's Shkreli Problem". The subtitle, "The most hated entrepreneur in America did a public service in some ways: he revealed a fundamentally flawed system that threatens an entire industry".

My investors expect me to maximize profits. Not to minimize them or go half or 70% but to go 100% of the profit curve. -Martin Shkreli

This is a logical statement for any C level executive in Biopharma. They are not put in place to make wise scientific decisions. That is the task of lower ranking members of a biopharma company. C level execs are put in place to turn a profit for the investors. On one hand this works. Without profit or the promise or illusion of profit, no one has a job. Gone are the days where we had people like George W. Merck.

We try never to forget that medicine is for the people. It is not for the profits. The profits follow, and if we have remembered that, they have never failed to appear. The better we have remembered it, the larger they have been.
— George W(ilhelm) Merck

How prevalent are the Shkreli types in biopharma? We know that he did not operate in a vacuum. He had a board of directors. He had investors communicating with him daily. He also had counterparts at Valeant. As the Forbes article points out;

Shkreli had learned about price hikes by watching his elders. In 2007 a mechanical engineer and former defense chief executive named Don Baily took over Questor Pharmaceuticals and raised the price of a drug used to treat seizures in infants, Acthar Gel, from $50 to $28,000 a vial, and then marked it for diseases like multiple sclerosis where there was limited evidence it worked. Quester was sold to Dublin-based Mallinchrodt for $5.6 billion in 2014.

So we really ought to look into theories that don't work, and science that isn't science... Who told Forbes that Acthar Gel had limited evidence that it worked in treating multiple sclerosis? Where is the scientific publication that takes on the scientific claims both positive and negative against a drugs efficacy? It doesn't specifically exist. We have science journals. We have people who work as scientists and communicate much better than the average person. But they do not outrank the likes of Shkreli and Baily. They live perilous lives searching for a livelihood within organizations like Valiant and Mallinchrodt. They cannot rock the boat. Medicine is for the profits.

From Forbes:

In 2005 a banker named Steven Harr pointed out that the only barriers to sky-high prices for cancer drugs were pharma "companies" goodwill and tolerance for adverse publicity" but warned his clients that they risked subjecting the industry to increased regulation and quite possibly price controls. (Harr is now the chief financial officer of Seattle biotech Juno Therapeutics.)

Steven Harrs career is typical of biopharma executives. He was educated in science but quickly turned towards the money. His bio on the Juno website states that he joined Juno in April 2014. Previously he was Managing Director and Head of Biotechnology Investment Banking at Morgan Stanley from May 2010 until he joined Juno. Prior to his investment banking role at Morgan Stanley, Dr. Harr was Morgan Stanley’s lead biotech research analyst and Co-Head of Global Healthcare Research. Dr. Harr received a B.A. in Economics from College of the Holy Cross and an M.D. from The Johns Hopkins University School of Medicine. Dr. Harr was a resident in internal medicine at the University of California, San Francisco.

Johns Hopkins! UCSF!!! Banker?

The likes of Steven Harr could have been a force for good. He could have been one of those looking after our interests in medicine. Instead he is now a top level executive at the Dendreon spinoff Juno. Not as their CSO or CMO but their CFO! Ironically the mistakes of Dendron have proven that Steven Harr was wrong about drug pricing. Dendreon priced their dubiously efficacious product/service way too high and they ended up filing for bankruptcy. While Dendreon lacked the public arrogance of Martin Shkreli, they share his philosophy on drug pricing. They know that the investors want them to go after 100% of the potential profits. Having stumbled badly with Dendreon and the high price of Provenge, they are now ready to take another shot at making money off of their biotechnology.

Threnanos 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?

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.

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.

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.

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.

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.

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.

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?

Sinatra

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.

Narrative

noun
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?

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."

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.

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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.

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?

How Can You Not?

http://www.opb.org/news/article/npr-scientists-often-skip-a-simple-test-that-could-verify-their-work/

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.

Why I Write

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.

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.

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.

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.

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.