Freakology, The Hidden Side of Life Science

What would turn up if we took a Freakonomics approach to uncover the hidden side of the life sciences?

Imagine having control over a small percentage of the NIH grant money. Wouldn't it be interesting to task a handful of scientists with a different sort of project. Take the approach that Freakonomics has taken in looking at "the hidden side of everything". They actually use the scientific method to examine that "hidden side". For example, they looked at Sumo wrestling in Japan. Observation: Using statistics they found that cheating was commonplace at the highest level. Each year the wrestlers must compete once a day for 15 days. If you win 8 matches you are advanced into the Sumo wrestling premiere league. If you lose 8 or more, you are not advanced. What they found through the powers of statistics this. A wrestler with a record of 8 and 6 would lose to his opponent 75% of the time when the opponent had a record of 7 and 7. Later, when the same two opponents met again, the 8 and 6 wrestler would win a majority of the matches. Hypothesis: The loss was a free pass into the premiere league for the would-be loser. The stronger wrestler now has a weaker field to face in the coming season.

Because Sumo wrestling is so revered in Japan, the mere idea of cheating was not to be entertained. Prediction of future observations: Freakonomincs authors Levitt and Dubner were convinced cheating was taking place. Over time people came forth and verified that cheating was a part of the Sumo culture at the highest level. In spite of the human habit of ignoring things for which we don't have an appetite, the truth had to be faced. Cheating was accepted as fact.

Let's take this notion into the world of professional scientists. Certainly there has been no appetite for an examination of the hidden side of their profession. We hold scientists above the common man with regards to honesty and self-policing their occupation. The creation of this "Freakology", funded by an NIH grant, would first have to face this obstacle.

The Freakology exploration into the hidden side of the life sciences would also have a similar purpose as Freakonomics, to entertain. Wouldn't it be a nice break to set aside the latest issue of Science or Nature for some light reading on the hidden side of your occupation? For those who do not believe it is appropriate, those who have similar brain function as religious folk or Sumo wrestling aficionados, we leave them to continue reading the latest study on RNAi knocking out protein X and curing disease Y. For those who see science as the only worth while use of our brains, let's see what this NIH funded Freakology has to say about us.

The first issue of Freakology. WHAT WILL GET YOU PUBLISHED! According to the journal Science:

Science's Mission: Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit the recognition by the scientific community and general public provided by publication in Science, beyond that provided by specialty journals.

There is a hidden side of science (not the journal Science) to be explored here. This description of a Science journal publication versus say that of a Biochemistry journal publication implies that Science editors somehow know what is "beyond" the specialty journals limitations. The proper application of the scientific method is not priority number one, although it is suppose to be assumed that everything they publish has gone through the rigors of our method and is thus reproducible. Beyond that trivial little issue of the scientific method, the editors of Science want sexy science. They want the stuff that will change the world in one paper. They don't want follow ups and detailed sharing of information. They want superior sounding papers. Papers that are "beyond" the rest.

The hidden side to publications in the more elite journals is that there is this built in bias towards more sensational analysis. In the case of Stan Prusiners first prion paper in Science in 1982, for example, the researcher who did the actual lab work at UCSF quit over the publication. He felt that Prusiner was overinterpreting the available data to push the prion hypothesis. No one is willing to admit that a scientist would overinterpret to advance their reputation. Yet in order to be published, Science requires your work to go beyond that of common researchers. This might in fact lead researchers to simply go beyond what the data is telling them. You are after all required to impress by going beyond. Once it reaches the journal, a truly non-scientific method begins. No one reproduces the work. No one is allowed to offer alternative explanations. It is the word of one man, and the et.al. who need the publication on their resume. The greater the "sexiness" requirement, the greater the risk for bad science.

By contrast, lets look at the life of Ignaz Semmelweis. While working at the Vienna  General Hospital in the mid 1800s he discovered that the doctors had 3 times the mortality rate as midwives. The doctors had been conducting autopsies in the basement then going straight upstairs to deliver babies. Ignaz proposed the rather un-sexy and , to some, insulting idea that the doctors needed to wash their hands. In one study the mortality rate of women giving birth at the hospital (10 to 35%) was reduced to under 1%. Ignaz was ignored. Later institutionalized where he died at the age of 47.

This is an old issue for some of us. To some however it would seem to be a hidden side. Long ago we did things that does not make sense to us now. In 100 years or so we will look at the publication model and laugh. With new technologies that can search for plagerism we can spot cheaters. We can conduct meta-analysis to find conflicting results. In time we will have more tools to replace the assumed superiority of the reviewers. For now we can only hope to shine a spotlight on the hidden side of our profession. The first step is to admit that there is a hidden side.

Pink Ribbons Inc.

Breast cancer has become the poster child of corporate cause-related marketing campaigns. Countless women and men walk, bike, climb and shop for the cure. Each year, millions of dollars are raised in the name of breast cancer, but where does this money go and what does it actually achieve? Pink Ribbons, Inc. is a feature documentary that shows how the devastating reality of breast cancer, which marketing experts have labeled a "dream cause," becomes obfuscated by a shiny, pink story of success.

"Instead of saying what has come out of these investments, they tell you how much money they've put in." 

Pink Ribbons Inc.

The 2011 documentary Pink Ribbons Inc. highlights a microcosm of Cargo Cult Science. Right around 47 minutes into this video (per Netflix) they start to ask hard questions of the science being funded by the Pink Ribbons money makers. What has been done, with regards to understanding breast cancer, as a result of all of the money raised? We know that the Susan Koman walks and Avon pink ribbons have raised money, and made a lot of people happy. The real cargo however is the productivity of breast cancer research. The productivity cannot be measured by dollars raised.

Who are the scientists supported with money from the pink ribbon people? What are the scientists doing? Are they on to something intellecually? Scientifically? Are they busy raising money? Do they understand the disease? Why in the hell have they not taken notice of the Amgen paper its ultimate discovery of how much payed-for and publilshed cancer research is of any use?

The inability to reproduce the work of ourselves and others is our greatest enemy. As I've often said, honesty in research is akin to honesty in a crossword puzzle. Purposely publishing non-reproduced research means that you have little concern for overall outcome of the body of knowledge to which you are contributing. Yet in our current system, the consequences of being discovered as "non-reproducible" are easily brushed aside. Blame a tech, blame someone or something, but never admit that you jotted down the wrong word in our proverbial crossword, because it benefitted your career.

Susan Koman and the Pink Ribbon people are not bad people. They raise money and that is a good thing. Where they leave the righteous path of actually doing something about breast cancer (or any cancer) is directly at the point of handing that money over to a small group of scientists. At that point we leave it in their hands. We have no way of checking on the validity of their work. The money goes into the hands of a specialized class of people who have convinced the world that they have some god like understanding of what we need to figure out. This special class does not want anyone analyzing their work. They do not want an accounting of the work. Simply accept the final word, which always comes with the line, "more research will be needed". More money will be needed.

Thoughts on Mackey and AstraZeneca

I talked about the biotech/pharma "South Sea Islanders" and how they arrange things but never seem to "get some wealth in their system".  Back in 2010 AstraZeneca (AZN) rearranged their cargo cult airport and hired Martin Mackey to be their new head of R&D. He has now been let go in yet another shake up of Cargo Cult research and development leadership. The new guys will come in with great expectations, just as Mackey did, and they will proceed to do whatever people at that level do. I don't know what they do. It's not science. It's a new arrangement in the Cargo Cult Airport of AZN meant to build wealth into their system. According to Fiercebiotech:

Now the global R&D operation will be divvied among three key players: Mene Pangalos, MedImmune's Bahija Jallal and Morrison Briggs. They will each be given one of three tasks: Head of discovery and early development of small molecules, running early-stage work on biologics (MedImmune's role), and late-stage development.

Pangalos has been an outspoken proponent of finding a more flexible, lower cost approach to drug research, championing the virtual strategy adopted for neurosciences work and shunning big investments in bricks and mortar in favor of a more open R&D environment. Jallal, meanwhile, has been pioneering new deals as well, recently inking a pact with a Chinese CRO aimed at shaving four to 6 years off the development time for one of her biologic programs. Morrison, meanwhile, is another survivor of the storm. He was brought in a year ago to head late-stage work after stints at Merck ($MRK) and Pfizer.
"This new senior executive team structure, that draws heavily from the leadership talent within the company, enables us to bring an even sharper management focus to key pipeline assets, key brands and key markets, and helps us further accelerate decision-making," said Soriot in a statement.     

I mentioned (in this post), that high ranking positions in any company are often judged in non-scientific, random ways. In "The Drunkards Walk" Leonard Mlodinow tells the story of, Sherry Lansing, the former CEO of Paramount.  She was the boss during a string of blockbusters like “Forrest Gump,” “Braveheart” and “Titanic.” She was hailed by the Hollywood press as a genius. After a series of box-office disasters however, she was replaced. After she was let go for her poor performance Paramount went on to have its best summer in a decade. Mlodinow pointed out that the new success of her replacement came from such like, “War of the Worlds” and “The Longest Yard,” that were in production when Lansing was still in charge. 

Martin Mackey certainly doesn't like what is happening to his career. He lived and died in a random system that he felt was not random. When he was on top it was a great system. Now? When Martin Mackey was given his turn it was not a good time. 

The Cargo Cult Airport has been rearranged. We look to the skies...

Lysenko

Soviet agronomist Trofim Denisovich Lysenko was a Cargo Cult Scientist. He had a job to increase crop yields. He did not succeed. He succeeded, in spite of his scientific shortcomings, at being one of the most powerful scientists in the Soviet Union during his lifetime. He is now considered an embarrassment. What can we learn from this dark story in the history of science and popular opinion. Certainly, if the opinion holders are influential human beings, opinions can trump scientific facts. At least until facts can no longer be ignored.

What led to the influence of Lysenko on Soviet science? We in the biotechnology business have had a similar problem. The influencers set up a system of conducting research that has been a failure. The rest of us bought into the prospect of riches and fame, in spite of our average minds. Is it possible that the social phenomenon that lead to the rise of Lysenko is infecting modern scientific systems?

Lysenko and the scientific method parted ways at the corner of Nature and Nurture. Lysenko did not believe in Mendelian genetics. He felt that the environment was a more important factor in the long run. For example, in 1927 Lysenko described a new method to fertilize fields without the use of fertilizers or minerals. The method was called vernalization. Germinating seeds were exposed to low temperatures under specific conditions allowing for human control of the plant's flowering time. In the modern world we could easily test his theories. Using design of experiment (DOE) one could create the series of growth experiments. Determine the variable, temperatures, lighting, soil, water... Undoubtably, there will be a sweet spot in which to grow your seeds. Lysenko, in this fashion, was not unlike many scientists today. Take a system in which something must happen, randomly test combinations of variables, and claim that you have discovered something. It is a useful process, testing variables via DOE, but something was missing in Lysenkos work.

Vernalization is a proven biological phenomenon. Lysenko however, utilized the cargo cult scientific method: Design research to reach pre-ordained results, ignore any results which do not advance your theories, report only positive results, and guard your career with Machiavellian political skills.  Lysenko pre-ordained that the process of vernalization could be inherited in plants.  He reported successful experiments that yielded healthy, robust pea plants in the dead of winter. Amidst the poverty and frequently frozen Soviet Union, Lysenko was portrayed as a hero of the Soviet state by the state-owned media.

That sounds familiar. For example, in biotechnology we pre-ordained RNAi technology as the next big thing. The media jumped on it, investors handed over billions and "news" organizations such as the journals and the lesser scientific reviewers such as Xconomy touted the coming of a new era in scientific advances. Finding cures for Cancers and Alzheimers was just a matter of time. Ironically, much of the research that I witnessed, and participated in, was very much like the work of Lysenko. If an experiment with RNAi did not produce the pre-ordained results, we were sent back into the lab to tweak the environmental variables. The temperature or CO2 in the incubators must have been off. Try again! The cell media needed to be tweaked. The measurement techniques were sloppy. There was always something wrong in the lab when the pre-ordained results were not obtained. Imagine one small lab experiencing this cargo cult scientific method, then multiply the experience by however much cargo cult work was generated by billions and billions in investments.

Lysenko was a successful man. In his day he accomplished his goals. Like most important members of a society, he was eventually deposed. He worked at the highest level, identified as a scientist, from the late 1920s to 1964. He never repented. He labeled his detractors as nattering nabobs and humdrum hirelings. He had power. When he lost it he was already an old man and people would remember that he was once here. However, in spite of his own opinion on his worth on earth, his name has become synonymous with bad science. According to Wikipedia:

Lysenkoism is used metaphorically to describe the manipulation or distortion of the scientific process as a way to reach a predetermined conclusion as dictated by an ideological bias, often related to social or political objectives.

That is an excellent description of Cargo Cult Science. Lysenkoism is alive and well. I worked under these conditions for years. The bias is related to careers and financial gain. Under our current system, nothing has to reach the market. No product needs to be sold to a customer. We sell potential. The science must be sexy and the potential profits must be identified and described eloquently to our real customers, the investors. Before a drug in the pipeline reaches its final destination, its own death, a few can have successful careers, like Lysenko. Success is merely getting another round of financing. At the lower levels, that of the tribesmen who work in the labs, success is another year or two of work.  The promise of biotechnology, like the promises of Lysenkos science, has not produced. My experience made me a skeptic of the leaders. It lead me skepticism, a word not allowed in the Lysenko approach to science.

The massive layoffs repeated year after year, the useless "Provenge" style products, the wasted educations, the 90% false published findings, THE AMGEN STUDY!, and the arguments against the Reproducibility Initiave are all part of our biotech Lysenkoism. The modern world of humans who thrive now, and who would have thrived under the leadership of Lysenko, are making a mess of science. The successful scientist interviewed in the Amgen study:

"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."

We are, after all, mostly average minds, trying to do what Einstein and Newton once did. We allow the successful scientist to operate in a "best story" environmnet. The leadership, such as Lysenkos, defines what is the best story. Nature is too tough to figure out sometimes. Sometimes we just tell the best story. But it's not science. It's Lysenkoism. It's a Cargo Cult Science.

Humdrum Hirelings and Dumb Followers

If you want to speak out against Cargo Cultism within science you should probably start by being someone like Richard Feynman, not a biotech laboratory worker. The leaders of biotech Cults may not fancy themselves as Cargo Cult leaders, rather real scientists like Feynman. Fools like me have a problem. Whereas the Cargo Cult leaders seem to lack that thing that makes science work, the common tribesman lacks that thing that influences others. Compare the following comments. The first comes from Douglas Fairbanks' book, "Laugh and Live":

Our natural aim is to make for ourselves a true personality that does not know defeat... How immeasurably inferior to such a spirit is the fellow who whines and moanes at every  evil twist of fortune. He has no confidence in himself an nothing else to do except confide his woes to all who will listen to his cowardly story of defeat. Such men are least useful in the important work of this world. They are the humdrum hirelings-the dumb followers. 

Next my friend from Allozyne:

Your posts are emblematic of someone who spends a lot of time complaining and little time actually working to try and make a positive impact a.k.a fighting the good fight. You couch yourself as a "leader" and yet your myopic POV is stark evidence that you have never sat at the "big boy" table nor been an influencer in any strategic decision... 

These two people, decades apart, separate vocations, never having met, would seem to put me and my philosophy in a nattering nabob category. A loser category. 

I was in fact a mere hireling. In my defence I am certain that I was hired to be a dumb follower. My attempts to alter that reality was met with great opposition. I turned to a simple blog to cleanse the mind. I've never thought of influencing anyone through this medium. To me this has been fun. Writing about the little things is enjoyable. Why does something like biotech, and scientific research in general, fail so often? It's fun to think that you might have a few thoughts on the subject. You are not just a humdrum hireling/dumb follower. In "Laugh and Live" Douglas Fairbanks offers up all kinds of advice on how to become the kind of fellow that was popular back in the early 1900's. In the Cargo Cult Scientist I offer up thoughts on a different kind of thinking. As Steve Jobs said, "Think differently". 

I came across an example of scientific/mathematic thinking that I think is important to this blog. Daniel Kahneman gives this simple puzzle to point out the battle between fast and slow thinking. "A bat and a ball cost $1.10. The bat costs one dollar more than the ball. How much does the ball cost?" The fast thinking mind comes up with the answer; ten cents. The correct answer is 5 cents. Think about it. I've come across this same mathematical error quite often among the tribesmen of biotech. For example, a one percent solution prepared by adding ten grams of solute to one a liter volume (not brought up to a 1 liter volume). It is a fast thinking error that is common. Does it matter? Is it complaining to suggest that fast (lazy) thinking is common in the life sciences.

In the above puzzle a common mistake is used to illustrate a bigger issue. An entire book from a Nobel prize winning scientist is dedicated to the subject. "Thinking Fast and Slow" should be required reading for anyone conducting research. You may think you don't make simple errors that arise from thinking too fast. Chances are you occasionally do. I'm not being a nattering nabob on this issue. I make simple errors and I don't think it is negative. The ambitious person may cover up their mistakes. Every time I catch errors I feel I get better at preventing them in the future. I even offer the scenarios up for others to contemplate, much like the common "ball and bat" math mistake described above. Not only do I point out my own mistakes, without guilt of having made them, I tend to point out the errors of others. I don't see the downside, perhaps because I have an un-diagnosed case of Asbergers. It is not the specific error or who made the error that attracts my attention, but the type of error that is made. If it is common we can train ourselves to be on the lookout. 

My response to Douglas Fairbanks and my Alloyzne friend would be that science requires a different kind of person. It requires people who prefer to think slowly and carefully. People who think slow are valuable people in the world of science. People who think fast are great in movie audiences or investor meetings. In science however we run the risk of promoting the "humdrum hirelings/dumb followers" because they are best at thinking fast and being a good follower. They don't know defeat... but they should. They may be too dumb to know they've failed. In science we know defeat. It is a small child dying of cancer or the grandmother/mother/sister/wife with Alzheimers. We have never tasted the success of a Douglas Fairbanks and his rise to Hollywood elite. We've never sat at the big boy table at Allozyne. We just don't care about those kinds of things. We want to succeed at something else.

My Allozyne detractor is someone I'd like to hear from again. I've taken his comments to heart. I've had the very same ideas leveled against me by a silent movie actor who died in 1939. I hear what they are saying. Am I a loser? That's rhetorical. In many ways the answer is yes. I am a bad fast thinker and a very slow thinker in general. It takes me a while to grasp the meaning of things.

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James Randi once created a fake guru to fool the people of Australia. He trained a young man to get on stage and talk to dead people and bend spoons and so on. At the end of the experiment they told the people that the young man was scamming them. The people didn't care. Many still believed in the young man. They wanted to believe the young man. Randi failed to demonstrate to his audience that they were easily fooled. He failed! I think of my failures in the same way. Perhaps I am right about this cargo cult thing. Maybe I am too harsh and there are degrees of CCS to this business. But this is not what people want to hear. The truth, even in the scientific community, is not as influential as more pleasant explanations.

Whether or not I could explain that the correct answer to the "Thinking Fast and Slow" example above to someone who doesn't think it matters, the fact remains that the answer is five cents. I may fail to convince others but I have a way of getting to the truth. That is what I consider success. 

Data Analysis for Researchers? Who Us?

Recently I was looking at the requirements for a data analysis certificate at the local university. Biotechnology takes data analysis too lightly. Certification in anything other than HR is unheard of. The qualifications of a researcher or someone who designs experiments vary greatly. One company may require very little of a person working in their labs. The next company may require a PhD to run their western blots. Who is analyzing the data coming from the lab? Is the data handed off to a specialist for analysis?
The requirements for the data analysis certificate are the following:

Select 10 or 11 credits from the courses below to complete the certificate program.

Required courses

STAT 511 – Design and Data Analysis for Researchers I (4 cr.)

STAT 512 – Design and Data Analysis for Researchers II (4 cr.)

Electives

Select a minimum of two credits from the following courses.
STAA 565 – Quantitative Reasoning (1 cr.)

STAA 566 – Computational and Graphical Statistics (1 cr.)

STAT 547 – Statistics for Environmental Monitoring (3 cr.)

Admission to the University is not required to earn the Certificate of Completion in Data Analysis. You can register for any course in the certificate program as long as you meet the course prerequisites.

Data analysis for researchers? What kind of research? The prerequisite math requirements alone are beyond what most universities require for bio or life science degrees. The degrees most prevalent in biotechnology do not have the same standards as those required to obtain the data analysis certificate.

I took a look at a few jobs in the local area to see if they required the same rigorous standards as the university certification. The Allen Institute for Brain Science is hiring a Scientist I. This individual will be required to "Work with experimentalists to understand their data and to suggest new experiments." What would the difference be between "understanding the data" as it is arbitrarily shared with you by the experimentalists (as AIBS requires) versus packaging the data and subjecting it to the analytical tools taught for this certification program?

Of the jobs available on the WBBA website, none require any data analysis certification. To obtain this certification would be very expensive. The upside is the wonderful knowledge you will gain. The downside is having a useless degree with regards to working in biotechnology. It would be like having a PhD in Aeronautical Engineering in the Cargo Cults.

Stinking thinking? No. This is an area ready for profit. If the Reproducibility Initiative were to one day mature into a world class tester of the tests, analyzer of the analysis, it would need an entire department of nerds with data analysis certification. Job requirement: Certification.

Xconomy Is Running Out of Cargo Cults

I've always felt that the role of Xconomy in the biotechnology industry has been to cheerlead. They are to biotechnology what FOX News is to the right wingers. Xconomy was organized with the idea that biotechnology and money were a match made in heaven. They have tried and tried but they just can't make this Cargo Cult look like a real airport however. Each biotech company Xconomy hoped to befriend was a fire along the Cargo Cult Airport. The fires burned out one by one until only a tiny handful remains. Tribes like Seattle have almost completely disappeared. What is left is nostalgia.

When the Cargo Cult Scientist began back in 2006, I was well into a career in an industry that involved routine mass layoffs. The layoffs were meant to halt the negative direction in which a company was headed. Flash forward to todays headlines from Biospace. Six of eight stories are about laying off staff.

1. Pfizer Inc. and the Incredible Shrinking Sales Force
2. Sandoz Inc. Closes Med Plant
3. AMRI to Close US Site and Shift Work to NY and Singapore
4. NeurogesX Inc. to Cut Jobs
5. Spherix Announces Restructuring 
6. Cumberland Pharma Lays Off One Third of Sales Force

Some things never change. The leaders have been changing direction since we began. Rarely do we revisit the certainty the leaders had when they began doing the thing that they later had to change. Rarely does anyone at Xconomy use our history in understanding our present. Why did those companies hire all of those people? What were those people suppose to have done? Where is the Cargo now?

Xconomy does admit that there could be a problem. In the article linked above, a former Icos (of Cialis fame) employee spoke of what she like about her current biotech job.

This person pointed out that the company was appealing in part because it had a decent amount of cash, which meant it could operate for at least a couple years.

This "this person" has a job. She is not going to change the industry. She does not question her leaders. She does her job and stays the course. She is just glad to think that the layoffs won't be coming for at least another couple years.

What does this "this person" do? Xconomy has never been interested science, just the business of science. The people down below who work for the security of "at least a couple years", aren't interviewed on Xconomy stories. Xconomy was formed to facilitate the conversation between the money and the takers. The people whom Xconomy is written for do not work in the lab. Like a Cargo Cult, none of the people in charge know how things actually work. They know money. The leaders read Xconomy because it offers a positive spin on the one aspect of the business that they care about, the money. The money is the cargo in this cult. Drugs and drug development is of little interest.

The money seems to have dried up. To what extent has this industry faced a reduction in funding, jobs, productivity... Xconomy has been "reporting" on this industry for quite some time now. They seem to have missed the real story. While the industry was steaming headlong into its own personal depression long before the rest of the economy went south, Xconomy was telling feel good stories about people getting rich and making awesome drugs like Provenge. Now they are left wondering where that old "can do" spirit has gone. Never mind that, what happened to journalism? 




 

Hollywood

If one were to study the origens of story telling, they might begin with cavemen and their paintings on cave walls. We are probably missing millions of years worth of information. No matter what we try and wrap our brains around we seem to only see the tip of the iceberg. I recently purchased a set of videos on the history of Hollywood. If you think it all began around the time of Edison you would be wrong. For a long time people had been gathering in darkened theaters to watch images of light flash by on a screen while music or some narrative played. When Edison et. al. came along they began with the simple fascinating images of people in movement. Not long after this novelty wore off they began telling stories. Science has turned out to be very much like Hollywood. Fictional stories are far more lucrative than documentaries that make you think. Peole prefer Batman.

Our history is like this history of Hollywood. Both began long before the era on which people choose to focus. All of the real science that went into creating both industries was exciting. The book "Silent Lives" describes the times of people in the early days of the motion picture industry. The book "Double Helix" describes the lives of two men in the early days of biotechnology. The early days were full of desperation and hope. We now know that success was obtained so we feel comfortable. The movies at first were short examples of pictures creating the illusion of motion. Nickelodeons offered very brief scences of a person jumping up and down or someone taking a walk. The Watson and Crick DNA structure paper was also short, one page long. The early days of both industries started with just the basics. We can show people in motion. We know the structure of DNA. Where do we go from here. We've come a long way.

An interesting side of the movie business is the throngs of young people who flock to Hollywood eager to make a living in the business. You hear about the success of Brad Pitt. He dropped out of college in his last semester. He worked as the El Pollo Loco chicken for a brief while and got a big break on Thelma and Luise. Who you don't hear about is Kathryn Carner. She is a lovely young lady with lots of talent. She never made it however. She is still out there being a creative person but she didn't make it like Pitt. When we think of Hollywood we think Pitt, not Carner. The truth is that Hollywood is both of them.

Now, likewise, when we think of biotech we think of Amgen. We think of Leroy Hood. Some people make it. Most people flounder. Just like Hollywood we have more talent than we can support. There must be some way of sorting out the ones who will make it. Who makes it and who doesn't? What science makes it? What does it take?

As we've often talked about here on the CCS, the narrative is something that all serious scientists take into consideration. The lesser men and women get their PhDs and go desperately searching for a job, any job. They may end up in Seattle or San Francisco. They may have a PhD in Microbiology and end up running a protein purification group at a small start-up. It is the serious scientist that forges his/her own path. David Sinclair, for example, knew that a Resveratrol career would get him tenure and a $720 million dollar biotech deal. Not many protein purification supervisors think big like that. It is that kind of dreaming that made Hollywood and biotechnology. Unfortunately for us, science is not all narrative. Where we part ways in comparisons is in the origens of our stories. In biotech it must be real. In Hollywood it just has to be interesting. In the Cargo Cults we prefer the Hollywood system.

Pills for Fat People

It's been a while since the leaders have offered up an anti-obesity pill. The FDA caught a little flack for the Fen Phen fiasco. The latest prescription diet pill, Vivus' Qsymia, came out recently but has seen slow sales. Maybe the diet and exercise secret has been let out. The real reason for this post however is something I came across while looking into the Vivus pill. I thought maybe Qsymia was PYY. Who would be so foolish as to try and make PYY into a diet pill and would the FDA approve such a thing. It turns out that leaders at the Novo Nordisk Cargo Cult put together a PYY program in 2011.

We first brought up the PYY story in 2006 when the now defunct Nastech crashed and burned in their attempt to make a drug out of the hormone PYY. In this post I pointed out the absurdity of this biotech company attempting to hammer this square peg through a round hole. Merck entered into a collaboration with Nastech but found no reason to continue pumping money into the project.

Novo Nordisk is of course an important and useful company, not a simple Cargo Cult. They have the experience and expertise to provide useful insulin products. They have plenty to teach us here in the Cargo Cults. At some point however, all companies run into a Cargo Cult area. They have to do research and someone will make the decision that will set newly employed scientific team on a path of no return. These new scientists will have only one choice, make PYY a drug or find a new job.

The question for the Cargo Cult Scientist is whether or not PYY is involved in satiety. Many scientist don't believe the research. As I pointed out long ago, not only does PYY fail to impress in the nasal spray form, it might just be another N-Ray in the life sciences.

Science 9 July 2004:Vol. 305. no. 5681, pp. 158 - 159DOI: 10.1126/science.305.5681.158


OBESITY RESEARCH:Labs Fail to Reproduce Protein's Appetite-Suppressing Effects

by Trisha Gura

"In an unusual joint letter in Nature this week, more than 40 scientists announced that they cannot reproduce the central findings of a 2002 Nature paper that showed that a molecule called peptide YY3-36, when injected into rodents, dampens appetite for 12 hours or more."

Once again we have a candidate for the Reproducibility Initiave! What would they do differently than Nastech, Merck, Novo, Dr. Bloom or any of the 40 scientists in the Nature letter lised above? Who could help resolve this issue? Let Novo take a stab at this molecule. But what about basic research? Is PYY what we think it is? Can anyone help us place bets on Novos chances?

Alnylam and Tekmira RNAi Cargo Delivery

Tekmira and Alnylam made the news this week after settling their legal dispute over the use of Tekmiras RNAi delivery technology. According to Xconomy they have:

agreed to resolve all their ongoing litigation, and that the companies have restructured and clarified their relationship, so that Alnylam still has a license to Tekmira’s lipid-nanoparticle delivery technology.

For $65 million dollars Alnylam gets out of the manufacturing contract and they have restructured the licensing agreement for the use of the Tekmira delivery technology.  In 2007 the two companies formed their alliance and further added to it in 2009 with a manufacturing agreement. Then came the accusations from Tekmira that Alnylam was abusing the relationship by using Tekmiras intellectual property to create their own delivery system and sharing information with a third party. One has to wonder why Alnylam would feel the need to improve such an expensive technology that they had researched and selected over the many other options. 

The way forward for these companies? Alnylam is going to take over the manufacturing and Tekmira is going to develop drugs. Xconomy, ever the biotech cheerleaders with a special fondness for Alnylam describes the latest fiasco:

But now each company is on its own, and can’t count on the other side for help. Instead of relying on Tekmira as a contract manufacturer, Alnylam plans to focus on doing in-house manufacturing of the lipid-nanoparticles that it needs to deliver RNAi drugs into cells. The company has been building up that capability for a year, he says, and it has enough capacity to make batches of its lead drug candidate ALN-TTR02 for clinical trials, and into “early commercialization” of the product, Maraganore says. Alnylam also has been focusing on building up internal R&D strength for RNAi delivery. Alnylam’s in-house delivery group developed some new technology that is enabling it to start the first clinical trials later this year with an RNAi drug can be given through a subcutaneous injection—which goes just beneath the skin and is generally more convenient than intravenous delivery.

They have built up manufacturing AND delivery R&D? After laying off a third of their work force in 2010 they turned around and laid off a third of the remaining tribe in 2012. According to Julie M. Donnely at the Boston Business Journal: 

The layoffs include high-level positions including senior director of biotherapeutics, a senior director of business development, a senior director of pharma operations and a senior director of information technology. Nine senior scientists and 14 research associates positions will also be eliminated.

When did Alnylam make this commitment to improving their manufacturing capabilities? What did they do? How much did they invest? Who did they snag from what CMO? What about the delivery system they have developed? What was wrong with Tekmiras? They aren't getting rid of the technology. They've only restructured the agreement. Now they have yet another delivery technology? What is going on with the delivery of RNAi at Alnylam?

Of course we don't really know anything about actual data at Alnylam or Tekmira. Tekmiras claim to become a drug development company is equally as bizarre as the continued existence of Alnylam. They deserved each other. With no clear path, each company will continue to zig zag their way to oblivion. RNAi continues to be our number one Cargo Cult.

Tamiflu You

We know that Cargo Cults do not actually succeed at obtaining cargo from airplanes that they summon to land upon the runways. Likewise the leaders of pharma cargo cults know that they won't make it rich curing or even effectively treating disease. Not that they wouldn't want to have effective drugs. It is actaully very difficult to put together a group of humans and ask them to participate in a group think experiment in which the outcome would be to cure some disease. Endpoints become the goal. Convincing the FDA to approve a drug by paving your own path then taking the FDA on a walk down the path is a skill. A little insider help can't hurt.

The real issue we have always had with Tamiflu is the basic concept that such a vaccine would be worth so much. Annual flu vaccines are merely random guesses that make people lots of money. All you need is a group of leaders to give their stamp of approval on the vaccine. Why Tamiflu?

The latest in this saga is an example of how the leaders operate and to whom they must answer. No one!

Last year, Tamiflu was included in a list of 'essential medicines' by the World Health Organization, a list that often prompts governments or donor agencies to buy the drug.

Our leaders have the clout to get governments to buy drugs but they lack to ability to get evidence that they work. In a democracy such as ours we don't get to vote on things like this.

Some might think this is switching gears too fast but stay with me. RNAi has long been my own personal Tamiflu. It doesn't work. It's useless. The latest bit of evidence here demonstrates that large profits can be made by useless things. And it all takes place on the Cargo Cults of biotech/pharma.

Our Cargo Cult leaders create huge promises and ask for huge profits. When they lose they go easy on us and only ask for less millions. They stop selling us the crap and keep the profits they already made. The cargo never comes.

Harry Makopolis

We need a guy like this:



We each have a story to tell. It leads to one of the biggest sins against science of our time. It's not just Silvia Bulfone-Paus or David Baltimore and their bullying leadership. Cumulatively we have a story that leads to a scam that has cost society hundreds of times more than Madoff. What we report in the journals is too good to be true. We aren't all that scientific. We aren't making investors money. We aren't having healthy careers. Something is a amiss. But our leaders are doing quite well. Where could we go to tell our stories and confess our sins against science? Would anyone listen?

Sinatra Was A Tough Guy

When you live a life like Frank Sinatra you leave behind plenty of film footage. There is one piece that I've seen on two separate documentaries. In the first documentary you see Sinatra surrounded by a bunch of burly men. They are rehearsing a scene for a movie while Frank is recording music at Capital Records. The thesis of this scene in the documentary is that Frank is a workaholic. In the next documentary you have the same film footage. It starts just when the rehearsing begins. 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. In this documentary they leave out the fact that the men are only acting. The thesis is that Frank really is the tough guy he is playing. 

The point here of course, is that context matters. Bullshitting, as I've mentioned, does not care about the truth. Bullshitting can take something that really happened, such as this Sinatra scene, and tell a number of stories. In everyday life we fall prey to such deceptions but they don't really harm people who take an active interest. In time, any Sinatra fan will come across the actual scene that took place in the first documentary. They will learn the truth. Frank is still a tough guy but he's not that big of a bully. 

What about stories that come from the lab of a published group of scientists? The stories that come out in the journals allegedly depict something that took place in a laboratory. The scientists who dictate the thesis behind the published work are not the guys who work in the lab. They are more like the producers of the latter Sinatra documentary. They begin with a thesis, they look for data/information that supports the thesis, and they present what they find. Some editing is required. The data/information that is left out often times will tell a different story. One in opposition to the original thesis. What then are the safeguards employed by journal editors and peer reviewers to avoid believing the wrong story?

I have written up a few of my experiences. Here is a cancer study using an antibody against denatured collagen. Here is a phage library that contains the holy grail peptide of RNAi drug delivery. Here is a computer program that pulls out drug targets from published information. Here is the origen of Prusiners prion theory. In each case I sat watching as a laboratory worker highly interested in the big picture science. What role does collagen play in tumor growth? How do we follow a drug molecule after it enters the body? Can we use published data, do we have enough information in the books, to begin to mine for molecules in a disease pathway. On each occasion I watched from my laboratory seat. I saw the whole scene, then read the version of the story that was published. Like Sinatra surrounded by his cronies, we had a scene. We had only to manipulate that scene, edit out the stuff that would hurt the narrative, and offer it up to the journals. Eventually some journal would accept the bullshit, and we could put the publication down on our resumes. After the publications, and maybe a patent or two, we would flounder with what we had put forth. We had to employ the political skill of saving face and distancing ourselves from what we said. If we couldn't use our science to advance our project goals, what were the chances of others succeeding? That was none of our business.

The cases I've listed are all MIA, missing in action. I can't track down the outcome of the work in which I took part. Long ago I had a role but I was removed through company buy-outs, lay-offs, temporary suspensions of projects and me just up and leaving. There is only one project that remains. It is the biggest scam of all. It is the 50,000 liter manufacturing claim from a company that expresses antibodies in yeast. The claim is bullshit. The bullshit claim was accepted by one of the major pharmaceutical companies. They shelled out over $100 million so far because the antibody may have a chance in demonstrating efficacy in comparison to the already approved drug. The question then becomes, can we make the drug in a cost effective manner to steal away sales from the competition? Like Sinatra and the tough guy scene, does the bullshit deception damn the project? Will that claim lead to another MIA biotech product? Would a full disclosure of the problems with manufacturing have prevented the potential loss of capital towards yet another biotech product? 

The potential loss in faith is something that is affecting everyone in biotech/pharma. Job losses have been massive. The promise of the science has not been realized by the scientists. We have to take some of the blame ourselves for not standing up and pointing out that truth. If we were in the room when Sinatra was rehearsing and someone is telling the story as if it were Sinatra being himself, someone should state the truth. Who will listen? Like the MIA projects from my own past, one has to wonder if anyone cares? Hundreds of millions of dollars of other peoples money is also MIA. I know where a lot of that money went. Cars, houses, and plenty of nice things by the people who were in the proverbial room when Sinatra was rehearsing. We all knew it was acting and we helped our leaders tell the world it was real. We get in our new cars and drive to our nice homes and hope we never get caught. 

Cutting Edge World Class Science Leader Wanted

I was watching the election coverage last night. Billions of dollars per candidate were spent and we are pretty much back to the same old people running the show. One of the talking heads lamented, "What could we have done by putting that money into medical research?" As if money equals progress.

Here is a prime example of how it does not. Intellectual ventures is a patent troll company that has made plenty of money from nonsensical science patents. They've decided to get into the biotech biz. Step one: Find someone who knows what this biotech BS is all about. They may have had to hire a consultant to write up this job description since the world leading research team needs to be set up by the guy they hire. I've added a few notes in red:

Job Description


Intellectual Ventures Laboratory (IVL) discovers, invents & develops advanced technology solutions in a wide variety of fields. With broadly interdisciplinary teams of physicists, engineers, chemists, biologists, and physicians, we attack pressing technical problems in energy, medicine, communications, and global health.

Purpose of the Position:

The purpose of this position is to set up and lead a cutting edge and world class biotechnology laboratory to support new technology development projects in fields as diverse as medicine, food science, energy, and renewable chemicals.

They have figured out how to become cutting edge and world class. HIRE SOMEONE ELSE TO GET THE JOB DONE!!!  I hope the guy they hires doesn't realize that his genius could be spent on his own cutting edge world class laboratory.

Responsibilities:

•Position is for a project leader who will be expected to develop clearly defined projects, lead small groups of scientists and engineers to complete the projects, and clearly communicate expectations and results to project stakeholders.

This scientist must cleary define the projects that Intellectual Venture Labs envisions as being fan-fucking-tastic. Beyond that IVL does not really know what their new genius has in mind. They do know that it will involve small groups of scientists and engineers. 

•Must demonstrate a broad knowledge base in the field of applied molecular biology and experience using project management tools to complete important projects in the field

They need a molecular biologist to lead engineers?
•Position is primarily a project leader role which requires frequent and clear communication with multiple internal and external customers and stakeholders.

•Limited travel required

•Must be able to lead biotechnology projects that broadly require manipulation of DNA, proteins, microorganism, and possibly plant and animal cells to solve diverse science and technology problems.

I'm getting the idea that they want someone to lead projects. Is the science getting a little broad here? The scientist must be an expert in molecular biology. This kind of scientist will manipulate DNA, proteins, microogranisms, and maybe... just maybe, plant and animal cells. These are the tools that will solve science and technology problems.  The "how?" is up to the new hire.

•Must help specify, purchase, set up, operate, and maintain molecular biology equipment and instrumentation as needed.

Ever seen a PI set up, operate and maintain lab equipment? What they have not specified yet is that they want a principal investigator with job functions at the RA level. 

•Must have experience leading teams which routinely perform several of the following kinds of tasks in the laboratory to solve problems:

•DNA manipulations including primer and gene design, routine PCR, vector construction, high throughput library construction. Pretty advanced buzz words in the mol bio biz! 

•Optimization of heterologous expression of wild type and modified proteins in various types of host organisms

•Engineering host cells via gene integration and gene knock-outs.

•Use of fermenters to grow and use wild type and engineered microorganisms

•Use of analytical instruments such HPLC and UV-vis to characterize proteins and engineered cells. We need a PI who knows UV-vis! 

•Must work with other technical teams (chemistry, physics, engineering) and customers to identify biotechnology needs and design projects to efficiently solve problems. It sounds like they've already started designing a project. 

•Must develop, plan, staff, and complete independent research projects in applied molecular biology

•Must safely work with biological agents, chemicals and compressed gases and coach others to do the same

•Must keep detailed documentation for all work and communicate results in clearly composed reports and presentations. A PI with a lab book.

•Must assist with the organization of data and other literature for reports and other communications and in files on the company’s server.

 
Qualifications and Skills:

•Master’s or Ph.D. in a Biological or Chemical/Chemical Engineering science. Excellent attention to detail skills. Chemical/Chemical Engineer indeed! 
What does a chemical engineer know about molecular biology?

•Degree and research experience in field which required extensive use of molecular biology techniques.
Didn't they just specifiy what your degree had to be? 

•Education and work experience that demonstrates fundamental knowledge of biochemical and molecular biology concepts and use of diverse array of equipment and instrumentation to do lab work in these areas.
So... molecular biology is required?

•At least 5 years of industrial project management experience in an active applied molecular biology laboratory and demonstrated success at defining and then completing those projects on time and on budget.

•Excellent verbal, written, and interactive communication skills are required.

•Being comfortable with freedom to explore is required
---------------------------------------------------------------------------------


I am sure I come across snarky. I can't help it. If the leaders judge us, why not judge them? This is their best effort in searching for the man or woman who will lead their cutting edge world class laboratory. The first thing the new scientist must do is make their small team cutting edge and world class. IVL has already started advertising their greatness. They designed their cargo cult airport. They just need a manager. It's up to the new guy to bring the cargo.  

The Brain Drain

Long ago, the Allied forces built and ran the airports that the cargo cults still to this day try to emulate. The aeronautics, logistics, geography and so on were put together in a system that escaped the observations of the natives. They recreated only what their eyes saw from behind the palm trees.

Likewise, the scientists of long ago created bodies of knowledge in a manner that is not practiced by the Cargo Cults of modern science. The first thing they held dear was reproducibility. Usefullness beyond ones career. As Newton pointed out in Principia Mathematica:

Rule I. We are to admit no more causes of natural things than such as are both true and sufficient to explain their appearances.
Rule II. Therefore to the same natural effects we must, as far as possible, assign the same causes.

First, these scientists of yore had to apply the scientific method to conduct their research, form explanations and causes. After years of honing explanations and causes they organized and wrote down their thoughts in the form of a text. They all felt that their understanding of mathematics or the natural world was worthy of passing on to future generations. Newton was so impressed with himself that he wrote Principia Mathematica in latin to discourage the wrong people from bastardizing his work. The great scientists of yore knew they were right and they had great confidence that what they had to say was reproducible and extremely useful. Lacking computers, the large collections of paper with hand written information were organized and kept until they day they brought them to the publisher. Therefore the information was in a very precarious position. What if a fire broke out? The information had to sit inside their heads until it was put down on that highly flammable paper. Lucky for us it has survived.
What then can we say about the body of knowledge that has been formed through biotechnology? Thanks to computers, it can be kept safe, if only someone were to take the time to write about our science. Occasionally we get ancillary texts. Lars Hagel, has written the seminal work on downstream process development. It's not a philosophical piece on how biotechnology research works. It's about one technology that is required in the business. He has published two editions of "Handbook of Process Chromatography". This is an example of good science. Anyone who has a job in downstream process development needs to read this book. Lars Hagel put it all down for the industry and future generations. He is just one example of a modern scientist who has something to say, people willing to let him say it, and an audience willing to listen and learn.

What about an individual company? I've worked for five. All but one no longer exist. The one that does is among the worst offenders when it comes to creating a Cargo Cult culture. If they were to write a text book for the benefit of others what would it say? What is the path from nothing to a drug on the market? What is that drug, what does it do, and how did we figure that out? It is not a simple nor is it complex. It is complicated. Thus, we could write a text book that is understandable to most people with an interest in science. We're not talking about Principia Mathematica here. The reason this text will not be written however is because the "scientists", all of whom have PhDs from very good schools, are now businessmen. They do not have the same interests that scientists of yore had. Rather than a text book laying out a lifetime of science, they have a string of biotech companies and executive positions. They have money in the bank. Yet the world will not benefit from their lives.

Who will even bother to make an attempt to put down in writing the science of biotechnology 1980 to 2012? We have ancillary texts like Lars Hagels book but it's not biotechnology. It's chemistry. It's physics. It's math. Drug development biotechnology is science, business, FDA regulations, clinical trial enrollment, patents, human resources, milestone payments, contract organizations, alliance management, and on and on. Many of these things will not be relevant to future  generations. The FDA will change (it must). The laws will change. The investors and doctors will all have a different set of rules. So what can we write a text book about? How to clone a piece of DNA? There are ancillary text books on this subject as well. The complicated task of writing a text book for future generations on how to create a successful science/technology company should begin with a similar set of rules as Newton. By now we should know that there are limitations to what we can do. We should also know that reproducible work is essential.
The leaders of the actual Cargo Cults in the Pacific Islands could write a book on aeronautics. It would be fun to read. If each tribesman could write out a description of their daily duties we could begin to study the leaders. Therein is the beginning of our study of the Cargo Cults of biotechnology. The leaders have many things in common. Likewise the tribesmen have things in common, that distinguish them from the leaders. There are patterns to identify and write down. There are philosophies to follow such as the preference for sexy narratives over boring reproducible science. The study of  biotech Cargo Cults however is losing very important information. With every round of layoffs from Pfizer, Astra Zeneca and so on, we lose a handful of long term tribesmen (and some leaders) to their inability to carry on. They take with them a knowledge of a daily life that we can learn from. Some of us learn a great deal from our mistakes. Each tribesman can speak of the mistakes they've been involved in. They can speak about the culture of their tribe. They can give us job descriptions and their titles. Did each watchman wear the same coconut headset and what did they do with it?

Once the information is gathered we would have to sit down and sort it all out. What were the trends? Was there a common thread among the success stories that the failures were missing? In the real cargo cults we could point to the study of aeronautics being absent among the cults but present in the Allied forces. If we were martians looking at this world we would come to the conclusion that aeronautics was essential. Likewise, to take a case from my own experience, Lars Hagels knowledge in process chromatography is essential. The company I worked for did not believe so and they had to suffer great expense. It is still possible this aspect of the company will be their downfall. If so, we could have an essential element to write down in our text. It comes with a philosophy as well. Process chromatography is an area in which a drug development company must employ highly skilled people, just as an airplane manufacturer must hire aeronautical engineers.

Our story is ready to be written. If you've worked in the business and you think you have something to say, organize our thoughts. Offer them to PLOS ONE and the Reproducibility Initiative. Someday the cargo culture will begin to shift. Someday perhaps, when Susan Koman wants to invest their research dollars will skip the Cargo Cult minefield and invest in someone else. Imagine a multi-million dollar project that involves reproducing work and finding the most promising paths to walk down. Imagine having the first edition of a text that will help lead the way. We've spent the money. We have thousands of minds to tap into.

It's not fire that threatens our text. It is our own apathy.

Who Wants It

I believe that future generations will look back on us as Feynman looked back to the middle ages:

During the Middle Ages there were all kinds of crazy ideas, such as that a piece of rhinoceros horn would increase potency. Then a method was discovered for separating the ideas--which was to try one to see if it worked, and if it didn't work, to eliminate it. This method became organized, of course, into science.

The idea of reproducing someone elses experiments is nothing new. What is new is the idea that such a project would create so much dissent. A piece of rhino horn used for erectile disfunction could be put to the test in a Viagra style study these days. It would be put to the test if some proponent of its use had the clout to get the research put in motion. Therein is the pickle we find ourselves in with reproducibility. The people with the clout are the ones whose work needs to be subjected to reproducibility studies.
Now when I talk about the actual Reproducibility Initiative I am using it as an example of one such effort to get the conversation started about what actaully takes place in the lives and careers of any modern day participant in the scientific world. I think any reproducible science, even boring science that doesn't rise to the sexy standards narrative science, is better than the cargo cult science. You can get rich, you can get published, but that is not the primary concern with this conversation. What I am thinking about is a Utopian world where the members of the cargo cult begin to be skeptics. They lose their jobs in the watch towers because, as their leaders informed them, they were not wearing the coconut antennas properly. They begin to question the antennas. They build confidence in their own ability to distinguish bullshit from the pile of clever sciencey narratives that their leaders pile on them. They discover a method for separating the ideas--to try one and see if it worked, and if it didn't work, to eliminate it.

Having started with this concept, that science began not so long ago with the idea of testing popular ideas, I'll address the comment from my last post. (Thanks for the comment btw)

As long as the incentives are not directed towards reproducibility, it won't be happen. The Amgen study was great but we didn't hear about until years after the original work and the authors had left the company and felt free to publish.

And of course we still don't know which studies or which labs were involved due to confidentiality agreements.

I'm not sure what is meant here. The incentives in reproducible science is that it leads to bigger and better things. We see so far because we stand on the shoulders of giants.

For academics funding is limiting and precious. If you tell an academic "here is $10,000 and you can spend it on reproducing your own work or you can spend it on a new project which will bring you more money and more publications", which will they choose?

Who would be so foolish as to give someone this choice? I've never worked with anyone who would volunteer for an outside reproducibility study of their own work. As I said at the end of my last post however, we have to be creative. Step out of the mindset of an academic scientist. Think in terms of a beaurocrat who decides on the NIH budget or an investor who wants to give biotech one more chance. You have a choice: Fund the same old guys who burned you back in the 90s and 2000s, or tap into a new paradigm. Only fund people who agree to have their work double checked. We're all only human. That is what the same old guys don't want you to know. Don't believe them. If they don't want the money, find someone else.

If you ask academics, all of them will insist to you that their work is reproducible so why would any of them consider trying to reproduce it?

Again, the academics are not the consumers (yet). They are the ones in whom we've lost faith. A Reproducibility Initiative must first do business with the consumers of good and bad science. The consumers can continue to lose money like they have in the past or they can try and see what certifiably reproducible work can do for them.

tldr: You don't get into Science and Nature by reproducing published research.

Again, no one is trying to get into Science and Nature here. They are trying to get Science and Nature to get into reproducible science.
Thanks to whomever this commenter was. You are absolutely correct with everything you said. The issues you bring up are the exact issues to attack. The question is how. Can we find a stunt like the Carnegie elephant crossing a steel bridge stunt? We have to be creative. The academic scientist is not the guy who wants a reproducibility group hanging over their research. In time however, the people with the money will come to find investments in reproducible science to be far more lucrative than the investments they made without this safety net. Soon scientists will have no choice, if they want funding, but to conduct the kind of work that will be subjected to reproducibility.

I know I'm only dreaming. But this is all just a thought experiment.

Beyond Science

One of the lesser arguments against certified reproducible results is that research will cost too much to reproduce. The past 30 years of biotechnology is a testament that this logic is flawed. Non-reproducible cargo cult science is expensive. Pharm research has wasted an estimated trillion dollars in the past decade. If you are into math and science, one trillion is an impressive number when we are talking dollar bills. Something must be done or the good that is in the life sciences will be put on a shelf until some other generation of people take a different path. Until then we will continue to lose our jobs while the bullshitters live out their reckless scientific careers.

What I mean by reckless scientific careers can be seen in the Amgen study. When 47 out of 51 oncology papers turn out to be non-reproducible you have a problem. People use this information. Scientists must rely on their peers but clearly they must do so only through the scientific method. Most scientists do not have the resources to try and reproduce 51 papers. They thus have to go on faith. Faith has failed. It's time to get science police on the job, armed with the scientific method, to go out and do the work that the average scientist cannot afford to do.

Andrew Carnegie made a few bucks in his day. He wanted the world to buy his steel because he felt that it was an amazing material that could be used in mass quantities as the world became more modern. Bridges, railroads, skyscrapers and the list goes on. He saw the power of steel as well as the financial power that was possible. In order to convince the people that steel was the latest greatest building material he put on a show. It was thought that elephants would instinctively not walk across a bridge that they felt would not support them. In a publicity stunt he had an elephant walk across a steel bridge. The bridge was of course strong enough to hold the elephant. People became believers with stunts like this and Canegie became the richest man on the planet.

Science is also powerful. It is used these days in the place of elephants. We can calculate what it takes to build long lasting bridges and tall buildings. But the kind of science we use in biotechnology and pharma R&D is not quite so strong. Currently that kind of science can be used to extract large sums of money from Cargo Cult Leaders and some of their followers, but it has not led to any revolutionary changes in health care. What could we do with the real power of science if it were forced to be strong, like the science behind the building of a bridge or a skyscraper?

Andrew Carnegie saw the potential in steel. Somewhere there must be a businessman/woman who sees the potential in keeping the life sciences alive with a reenforcing steel like force that keeps the companies and the papers from crumbling to the ground the moment someone tries to use them to advance our field. It will take vision and showmanship. Someone must begin to demonstrate the strength to fight against the nay-sayers. Who will our Carnegie be? Has he/she been born yet? There are many reasons why any reproducibility initiative will fail in the world of science. We need to start thinking about why it will succeed. I think that good reprocuble science will make us a whole lot more money the the Cargo Cult Science.

The First Reason

The first reason the Reproducibility Initiative and other efforts by PLos will succeed is because science is king. The scientific method is the most powerful tool we have as humans to understand our world and how it actually works. Religion has not given us indoor lighting or airplanes. Politicians have not given us a sustainable government. Scientists on the other hand have provided us with a body of knowledge that not only helps us now, but will help those in our future. We have an obligation to get it right.

We have a built in Reproducibility Initiative in our science education. The Merck Index lists a number of physical constants that are... reproducible. The are constant. Water, for example, boils at 100 degrees. We send our students into the laboratory to test that constant. I have yet to hear of a University where students discovered that constant to be wishy washy bullshit. You couldn't write up a paper on the fact that water boils at 100 degrees. You can't convince a journal that this has new and interesting applications. But if you get yourself a STEM degree, you will be taught this little fact. Why? Because it is useful reproducible information.

As I've mentioned in the past, research is like a crossword puzzle. When we get something wrong, but think that it is right, we trip ourselves up in the method. That method, the scientific method, is a method of solving a far more complex puzzle. Their are no individuals who are going to solve a complex puzzle such as cancer. Science will solve that puzzle. Each scientist must offer up their small answers with absolute certainty that they have something of value.

Arrogance, careerism, greed, desperation are a few excuses for jotting down the wrong answers without regard for the subsequent consequences. The greater problem is allowing for these wrong answers, and admiring those who provide them for the rest of us, thus hindering the progress of science. Science is powerful. Scientists are only men and women. What we must admire more than the people, is the science they leave behind. Real science has always opened doors, for good or evil, that lead to a new world. Throwing money at a biotech company or a cancer charity is simply wishful thinking. Wishful thinking is not science. If we respect science, we must subject it to rigorous standards. The status quo of publication is wishful thinking. The status quo is a mockery of the scientific method. The old white haired men who rule over their journals, never testing for reproducibility, looking only for sexy new narratives will never do to science what the boring old "water boils at 100 degrees" concept of science has done. Science has to be reproducible. When that happens the power of science is unleashed. When our first concern is financial or any other issue, we are misunderstanding the role science has played in our lives. We must get it right, or we are no better than a religion or a politician. Science is where we leave our hopes and dreams behind to allow reality to direct us in our pursuit of understanding the world we live in. Our first concern must be scientific integrity.

Fame on fortune will follow. The Reproducibility Initiative (or any idea/effort along these lines) will make your personal hopes and dreams come true because science is that powerful. When you put anything before that thing that Feynman speaks of, the concept of science over cargo cults, you begin to lose what science really is. You lose what science can do for you. You end up with a biotechnology company or a pink ribbon bumper sticker. Those things we hope for can come true if we stay focused and believe in science. It may not seem possible now, to have a for profit initiative to clean up the mess left behind by some scientists, but the power of real science, reproducible science, will make it worth our investments. In the future, scientists will scratch their heads and wonder why humans could have been so foolish to have had a system that did not attempt to reproduce what the leaders were putting forth. The same as we look back scratching our heads at the Salem witch hunts or using leaches to cure disease. It is merely scientific progress. That is first reason any efforts to highlight reproducibility matters.

Doing The Dishes

Paul Ryan's dish washing scandal has Inspired me to keep going. Any person who can stand in front of other people washing clean dishes is clearly a Cargo Cult Leader. Why? Because the purpose of washing dishes is to make dirty dishes clean! Paul Ryan washes dishes to create an illusion like we in science use big words and wear white lab coats.

I won't prattle on about it. It's funny. It's a man who would be be equally successful had he pursued a career in science. A leader knows the dishes needn't be be dirty when the objective is only to convince people you are cleaning them. Put on proper attire, look like you are working...

Thus I must return to this project. The Cargo Cult Scientist took a little break. No excuse. Nothing to report. The world is still ruled by men who wash clean dishes. I want to talk about the reproducibility initiative. Next post. Why do we need it?

While checking out at Safeway lately, I've been asked to donate a few cents by rounding up my purchase to the next even dollar. I refuse. Knowing what goes on in research I refuse to give. I would give to the International Peace Love and Harmony chairity if there was one and I thought they could achieve such a goal. The same goes for breast cancer (or any cancer) research. I would give them money if I thought they were fighting cancer. I do not. Not until they have checks and balances would I consider their work to be worth a penny. Cancer charities need accountability financially and scientifically. The reproducibility initiative is what I where I would donate my money. It would be indirect however. The initiative needs to establish its efficacy in sniffing out bullshit and the bullshitters. It needs to gain the respect that the life sciences have failed to achieve.

Imagine a huge fund raising event to raise money to test the efficacy of the Reproducibility Initiative. Those who feel it cannot succeed, here and here for example, are the same who think biotech companies can succeed. Cargo Cult leaders! I think this will work. If Ryan Paul can be a successful politician with ideas such as washing clean dishes, then science can succeed by creating the illusion (at least) that we care too. And we have got the scientific method on our side. Some of us really do care. We care more than we care about our own careers and our venture capitalists careers. It's science that is in trouble these days. The way it's practice. The way moneyed interests profit via Safeway fund raising events. The cancer we face is the lack of reproducibility from more successful cheaters and bullshitters. More successful people like Paul Ryan wash clean dishes and nobody needs that. Science has always had its fakers but lately they've cut into our credibility and there is a way to fight back. Test the tests. Research the researchers. More later.

The Big Boy Table

Dedicated to my anonymous reader from Allozyne:

Many years ago While as an undergrad I came across a most unusual man on public tv. He was a communist, pacifist and so on. He never cut his hair. Each week he would go on public tv and espouse his views, most likely because others around him had no interest in his interests. He needed to get his thoughts and ideas out and it was easy to secure a little time on local public tv. One particular criticism of him sparked my interest. A young student called in with no interests in the communists message. He wanted to know why the guy never cut his hair. It was meant to be an insult. To his surprise the host of the show had an answer. I won't go into it. The point of the story is that there was a person who was not like the people I grew up with. That is why I went to college. It was an experience unlike any I had ever had. This long haired old hippy with his own tv show was different. The young man with the "long hair" insult was what I was used to. The norm would have been to accept the insult and offer one in exchange. Instead the answer was legit. He really had a reason his hair was so long.

Flash forward to my crazy blog. I started writing little essays on the plight of a lab tech working in an environment that I cosidered hostile to science. I used Feynmans Cargo Cult Science commencement speech to address some of the problems I see in methodology. Like that old hippy on public tv, I throw out my ideas, ill concerned if they will ever be heard. Along comes a man representing the norm. This man, like the young man concerned about hair length norms, is appalled by my lack of adherence to our shared authoritarian system.

Rather than accept the insults I will address the sentiment behind my perceived lack of influence and career success. I am no longer working in this environment. I saw the influential is people most successful in groupthink.

Group members try to minimize conflict and reach a consensus decision without critical evaluation of alternative ideas or viewpoints. 

 To my anonymous friend from Allozyne, I want to say that the big boy table is a place I was never a place I wanted to be. It is a place of groupthinkers involved in something I call bullshit. The big boy table at most any biotechnology company that has ever existed represents the most successful people in the Cargo Cults of science. Like the big boy table at Mary Kay Cosmetics or DNKY, it is a table surrounded by people who do things in life that I don't care about. I care about the scientific method, fairness, piecing together a long history of research hits and misses that eventually solve an unknown that others will be able to use in the form of technology. 

I wish I could be more like the old communist hippy on my local public station. The problem is that I like new cars and a semblance of normalcy. I put up with the leaders of the Cargo Cults because I made more money. But at the end of the day I had to admit that I was wasting my education and my brief opportunity to contribute something. So I do have my little blog. It isn't meant to illicit insults but I understand. It's pretty insulting at times. That is life. Look at it from a viewpoint outside of the big boy table: