A Day in the Life Sciences

Typical day on Biospace, May 30, 2012:

1. STADA Arzneimittel AG to cut 800 jobs...
2. J&J Fails to win FDA OK for daily HIV pill...
3. FDA warns J&J over vaginal products...
4. Alnylam Pharmaceuticals lung drug fails mid-stage trial...
5. Flexion Therapeutics reports positive data for osteoarthritis drug...
6. Bristol Myers Squibb Company drug seen helping attack lung cancer...

Six stories, 800 job losses, two failed drug trials, one FDA warning, and two companies reporting positive data.

Early stage - positive results: "These results represent a significant advance..." "This could be a breakthrough..." "It's a turning point..." Actual quotes from these stories

Phase IIb - mitigated failure: "The study missed the primary endpoint... We believe that these data provide important evidence..." 

FDA review - failure: "The company said it is reviewing the FDA's response to its marketing application and it plans to respond as quickly as possible."

FDA Warning - "The regulator said it could not determine the adequacy of the company’s responses until J&J completed an investigation of each one and provided them to the FDA."

Notice how the people cheerleading the narrative start to fade away as a drug moves further down the line in development. The narrative starts to show signs of fallibility and the story tellers walk away. They are the positive ones. They are the ones who say things like "significant advance" and "turning point". They  are not the ones who say, "missed the primary endpoint" or "failed". In the end the leaders slip behind the curtain of Oz and let the Wizard speak. We are left with that empty feeling when something happens, good or bad, and we don't know why. 

Our Method

Descartes "Rules For The Direction of The Mind" can help the Cargo Cults understand "what is missing", why there is no "wealth in their system".

Rule 5 holds that complicated problems should be reduced to their simplest parts. We then apply our “intuition” to the simplest parts and work our way back to the larger problem. 

For our purposes here today, let's re-create a failed drug research project that most biotechnology companies in the past 30 years have attempted. The project is to make a drug against TNF apha.

Planning:

The norm is that the executive staff and the board select a drug target based on profit potential and the probability of success. This involves faith in the sound decisions of the board of directors, advised by the scientific advisory board. The target is TNF alpha.  

Descartes: Rule 3 states that we should study objects that we ourselves can clearly deduce and refrain from conjecture and reliance on the work of others.

While others had proven TNF alpha to be a target that can bring the cargo, most TNF alpha projects failed. The notion that TNF alpha projects have a high probability of success is false. What the leaders tend to do, when selecting drug targets, is disguise conjecture as a scientific method.

Execution:

Have the lab staff find a molecule that interacts with the target selected in step one. For our purposes we will generate an anti-TNF antibody.

Descartes: Rule 5 holds that complicated problems should be reduced to their simplest parts. We then apply our “intuition” to the simplest parts and work our way back to the larger problem.

The larger problem is getting the molecule to validate the conjecture and assumptions of management. The simple part is good biotechnology. We know how to make the antibody. Although this knowledge fades as we go higher into the ranks of leadership, it is a very solid foundation that gives the biotech credence. Where we begin to fall apart is when we move from the known technology into the unknown outcome of drug testing.

Analysis:

Descartes: Rule 2 holds that we should only study objects about which we can obtain “certain and evident cognition.” It is better not to study at all than to attempt a study when we can’t tell what’s right or wrong, true or false. 


In my experience scientists at higher levels do not participate at this level. Each company has different methods, for example, on testing the binding affinity of their antibody. Some use biacore. I've been told to do the same complicated calculations from ELISA assays. The higher ranking scientists need only have a vague idea as to how a drug is being tested at the early stages. Those who required me to obtain a binding constant from an ELISA assay, had a vague idea of how things work in the lab. In order to know whether or not the test will lead to "certain and evident cognition" much more attention would be required of the higher ranking scientists. This is a critical moment in the process that is soft. If the data comes back saying, for example, that the antibody had a weak binding affinity to TNF, the laboratory staff must explain why they think that to be the case. In other words, the lab staff must convince the scientists what the truth is. The scientists have positioned themselves only to judge the methods employed by the laboratory class rather than participate in establishing that an assay will provide certain and evident cognition. 

I've simplified the process down to its basic components. Where Descartes had rules for the direction of the mind, we have a very different set of rules. For each Descartes rule, we have a very specific unwritten rule of our own that does not match.

Rule 4 proposes that the mind requires a fixed method to discover truth. A method is defined as a set of reliable and simple rules. The goal of study through the method is to attain knowledge of all things. The human mind begins life in a pure state, and from the moment learning starts, the mind grows clouded. The method’s purpose is to return the mind to that pure state so that we can be certain of knowledge we attain.


As I've stated, there are no written methods for the larger problem. The simpler problems, (cloning, purifying, etc) have detailed written methods, SOPs. The laboratory staff must also write down specifics in a lab notebook, which often comes with a set of rules the lab staff must follow. Date each page, initial cross-outs... The scientists at the higher level have no method, no rules and no police other than themselves. Their commitment is to the illusion of success. Even if your biotech company fails, you now have experience running a biotech company. A publication is a publication, reproducible or not. Is this what Descartes outlined? 


We have a random method of discovery. It's a broken system. Reproducibility, to ensure that we are dealing with the truth, is not a part of our system. What would our rules be if we were forced to write them out in an attempt to explain how we spent so many billions on failed TNF projects? Failed Amyloid beta projects? Regardless of the target, the company, the technology, we would find a pattern. There is no set of reliable and simple rules. When you look into the laboratories, you will find that the minds have grown cloudy. If you look into the offices, you will find that the minds have grown corrupt. We need a method to return our collective mind to that pure state that led us to certainty in the past. 

A Wealthy System

Is Science the same system it once was? Feynman said:

they follow all the apparent precepts and forms of scientific investigation, but they're missing something essential, because the planes don't land. Now it behooves me, of course, to tell you what they're missing. But it would be just about as difficult to explain to the South Sea Islanders how they have to arrange things so that they get some wealth in their system.

We know that even the most productive scientists cheated at times. In order to stay on top a person has to continue producing. That just isn't in our nature. We grow old and we get lazy. There is probably a productive time in our lives where our minds operate best in the abstract concept of science. Therefore we need a method. We need to participate in a system that keeps us honest and productive.

Wikipedia says:

Science (from Latin scientia, meaning "knowledge") is a systematic enterprise that builds and organizes knowledge in the form of testable explanations and predictions about the universe.^[1] In an older and closely related meaning (found, for example, in Aristotle), "science" refers to the body of reliable knowledge itself, of the type that can be logically and rationally explained (see History and philosophy below).^[2] Since classical antiquity science as a type of knowledge was closely linked to philosophy. In the early modern era the words "science" and "philosophy" were sometimes used interchangeably in the English language. By the 17th century, natural philosophy (which is today called "natural science") was considered a separate branch of philosophy.^[3] However, "science" continued to be used in a broad sense denoting reliable knowledge about a topic, in the same way it is still used in modern terms such as library science or political science.


Even the definition of science is subject to evolution. The system changes. Currently it seems to have devolved into a religion. Is "science" the same systematic enterprise it was when Einstein was publishing papers in the early 1900s? What about when Descartes was working on his text books?

In Descartes day it was admirable to establish a body of work, not just a large quantity of publications. Not only did you set forth ideas, you used them to set up the next set of experiments. To go even deeper he wrote "Rules For The Direction Of The Mind". Rule 1 states that whatever we study should direct our minds to make “true and sound judgments” about experience. The various sciences are not independent of one another but are all facets of “human wisdom.” Possession of any kind of knowledge—if it is true—will only lead to more knowledge.

Does that resemble the system we are currently in? Once again, The Amgen Study:

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."

If in fact we had the same system that Descartes was participating in, what kind of text book would the anonymous scientist who told "the best story" intend to write? Is this a wealthy system?

We do have a system and people can learn that system and have long successful careers. It is not however, the science of antiquity. No one intends on writing a text book that will be examined by the best minds in the scientific community. Their work is not intended to be examined in the laboratory. It is sciency (pronounced - science-ee). You take the rules from Descartes, for example #3: we should study objects that we ourselves can clearly deduce and refrain from conjecture and reliance on the work of others. Now you have a method. Take the work of others, and rely upon it and get others to get the rest of the community to gravitate towards conjecture. Conjecture: a proposition that is unproven but is thought to be true and has not been disproven. Karl Popper pioneered the use of the term "conjecture" in scientific philosophy. Conjecture is contrasted by hypothesis (hence theory, axiom, principle), which is a testable statement based on accepted grounds. Our system is sciency. Work on conjecture; things that are thought to be true, such as RNAi. Don't design experiments that will jeopardize your conjecture. When an experiment does not prove your proposition, try try again.


Karl Popper was a philosopher who argued for a change in the system of science. He went deep. "Logically, no number of positive outcomes at the level of experimental testing can confirm a scientific theory, but a single counterexample is logically decisive: it shows the theory, from which the implication is derived, to be false." Where do we go from there after the Amgen study? The answer, in our current system, is to move forward ignoring the falsified studies. The 47 papers that were not reproducible shall remain anonymous because our system is not that of Karl Poppers. It is in fact, the opposite. The Amgen study matched up with the science of Dr. John Ioannidis. 90% bullshit is the current rate of scientific publications. In the labs of biotechnology the daily grind is much the same. The philosophy of yore is not a part of our system. We make money by doing what we are told. We have a very sciency life. Take this antibody or RNAi and bring me evidence that it reduces tumor size. Bring me evidence that it can be used to treat Alzheimers. I will use it in a slide presentation to extract money from investors.

That is our system. I imagine a system where the NIH opens a branch that randomly takes publicly funded research to the lab. The concept that we self-police should be abandoned. Someone needs to start policing the bullshitters. The scientist who receives public funds should be part of a system where they are randomly selected to come to Maryland and reproduce their work.

As Descartes suggests:

The human mind begins life in a pure state, and from the moment learning starts, the mind grows clouded. The method’s purpose is to return the mind to that pure state so that we can be certain of knowledge we attain.

Our system has grown cloudy. We have great minds of yore to help us out of this mess. The question is how do we get our leaders to follow the methods and philosophies that created this thing called science? It was once a very wealthy system. It is now dirt poor, ran by financially wealthy people.

The Comment Section

Some of the most interesting things I read online are not the articles but the comments people make. A few of my favorites:

I'm a productive postdoctoral researcher in the biomedical field; my work has brought about $5 million in grant money into the lab.  My career path is to transition from doing the thing that I wrote my thesis on, that I am the world expert on, to being a lab manager and writing grants.  It baffles me that the normal career progression in academic research is to take good researchers and turn them into bad managers.

That's a comment from this article written by Derek Lowe. I came across another comment from Dereks blog, "In the Pipeline" that lead me to another blog by the commenter. He discusses why we have so many layoffs in pharma R&D:

The longer answer is that we don’t understand what’s going on inside cells and organisms well enough to even know what we want a drug to target.

If you put the two comments together to try and solve the problems of drug discovery you have got something that no one wants to admit. We take the people we train to understand what's going on inside cells and organisms and we put them to work doing something their education can't help them do. The companies use the credentials of their scientific employees for purposes other than conducting science.

I enjoy reading Xconomy every day. Mostly I'm looking for stories of the Cargo Cults of Seattle not getting their cargo. When I conjure the image of the natives of a cargo cult gazing to the skies during their ceremonies, looking for the big metal birds carrying cargo inside, I think of Xconomy as the sky. Sadly they don't illicit many comments.  The lack of an active conversation indicates that people are not engaged.

One of the criticisms of the commenters is that they are often anonymous. Comments are little blurbs from self appointed "wise old sages" who have to get their words out. Why don't they tell us who they are? Some are picking a fight. Some are expressing their concern. Some are just trying to be witty. Not everyone accomplishes their goal but the anonymity makes the possibility of failure a risk they are willing to take. The anonymity can lead to troll behavior but it can also lead to insights we wouldn't not have had on our own with the article. Anonymity is what we see from many scientists. They are absent from the lab and the many failed experiments based on their ideas. If you were to look into the laboratory notebooks of the young people who conduct research inside the lab you will find no mention of who told them to do the work. There will be no introduction outlining the thinking of the actual thinkers. Anonymity is a tool we all use.

Some comments are interesting in their defense of Cargo Cult thinking. In a recent retraction from Gerold Schuler, one commenter came to his defense:

Unless I am mistaken, Dieckmann is the corresponding author on this paper, so some caution should be exercised when going after Schuler. 

The commenter is "going after" another commenter. Going after people is common in the comment section. Going after a big time scientist is not common. They are exalted leaders. We here on the CCS recognize the amount of bullshit being put forth by our exalted leaders and we see no reason to mitigate ones speech when commenting online about their bullshit. Another commenter adds to the conversation about Gerold:

As early as 1997 the investigations started on some of the german investigators. Here is an example:Nature 387, 750 (19 June 1997) | and in 2000Abbott A: German fraud inquiry casts a wider net of suspicion…Nature 405, 871-872 (22 June 2000) | doi:10.1038/35016207Few names included in this report are currently directors of institutes…

Machiavellian Leaders? Is this how they reach that level were "going after them" requires commenters to exercise some caution?

There is power in the comment sections that is beyond the power of prayer. In prayer you throw something out there and you hope change will come. In the new world of online conversations we speak to actual people which gives us the ability to heighten awareness. Here on the CCS we try to "go after" bullshit in the world of science. We don't like that the bullshit and the master bullshitters make a career steeped in honesty nearly impossible. Real science is "bend over backwards to prove yourself wrong" honest, as Feynman instructed. The Machiavellian competition makes life hard on those who have a heightened sense of fairness. The comment section is an outlet. It's a place to exchange ideas and challenge each other.

The real challenge for a website is to get visitors. Facebook has demonstrated the power of online traffic. Huffington Post also made a fortune by getting people talking. The comments online are different than the comments you make at a cocktail party. They are different than the comments made at a cancer conference. They are more honest. Less intelligent in general but more honest. Perhaps the science community needs to purposely "go after" the illusion of intelligence and open the doors to the "back and forth" one sees in the comment sections. We might get a little more honesty, thus wealth, into our system.

Investments Gone Bad

Ipierian is now an Antibody company!

Ipierian, founded in July of 2009, is the combination of two companies, Pierian and iZumi Bio. Pierian was co-founded by George Daley, Doug Melton and Lee Rubin, from the Harvard Stem Cell Institute. iZumi Bio came with the leadership of Corey Goodman, chairman, and John Walker, CEO. John Walker served as a Director at Cargo Cult favorite, Geron.

iPierian’s has had four CEOs John Walker, Mike Venuti, Peter Van Vlasselaer and now Nancy Stagliano. The chief technical officer, Berta Strulovici, exited the company shortly before Venuti. The heads of finance, business development, and legal/intellectual property left shortly after Venuti. A few weeks later Corey Goodman resigned his position as chairman of the board and Doug Melton, gave up his role as a scientific advisor.

Originally the business plan was to use their stem cell technology as a tool for screening new drug candidates, and selling their services to Big Pharma. The company’s technology is used to coax ordinary adult cells into a stem-cell like state. The cells are known as induced pluripotent stem cells (iPSCs). After an iPSC line has been differentiated into the cell types of interest, a disease phenotype is investigated, revealing a disease-relevant difference between the patient-derived cells and those from healthy controls. From this disease phenotype, cell-based assays are developed to enable the discovery and validation of novel targets and molecules.

Enabling the discovery and validation of novel targets and molecules was the Cargo. The company was the airport. The Cargo never came. There was no wealth in the system. The airport has undergone several shake-ups in management and some remodeling of the runway. Since Big Pharma didn't buy into the airport, iPierian has no choice but to develop the drugs they were hoping big pharma would. We still have to wonder if underlying technology real or is it another fantastic narrative?

The big name scientists told a good story. The problems came when the narrative failed to fit the reality being faced in the laboratory. Without the promise coming true the executives began to fight. The company is now an antibody company with a stem cell twist. The new CEO, Nancy Stagliano is a neuroscientist by training. Her last startup (South San Francisco-based CytomX Therapeutics) is an antibody drug developer. 

The only thing that matters is the ability of the technology to "enable the discovery and validation of novel targets and molecules". Management is secondary in the long term of this company.

iPierian has spent $50 million dollars to reach this point:

iPierian used its stem cell technology in recent months which has given it new insights about targets to go after on the Tau protein and in the Complement pathway.  

- Nancy Stagliano 

Recent months? I guess the first few years were spent firing CEOs. The latest CEO was busy on her startup CytomX Therapeutics.

Our novel platform represents a transformational drug discovery and development approach.

That sounds familiar. The chairman of the board is also the chairman of Geron! Why did Nancy leave CytomX? Why did the iPierian leaders abandon their ship? Who is suppose to solve the problems created by the others? I don't have much hope that iPierian is not Cargo Cult. All of the signs are there. The founders are gone. The new leaders are doing what they did at their last job. Everyone at the top seems to have worked with each other before. That wouldn't be a bad thing if this were a more successful industry. Lots of money has been wasted and people are trying to get some of it back. Think gambling. The most difficult problems facing the company is in drug discovery. All of the PhDs from the best schools are out trying to get money from investors. The laboratory staff have been handed an exact path that they must take to success. If they fail, they lose their jobs. Money is running out so they had all better start succeeding.

Look to the sky. Hope the planes come.

Books

I've been reading a book written by the silent movie actor Douglas Fairbanks. It's called "Laugh and Live". It's written in a style that must have been popular back in the 20s and 30s. Very positive and nothing but self help advice from one of the most successful guys of that era. Fairbanks must have felt loved and he was giving back. I'm on a chapter now where he talks about good books.

Books by such men as Marden and Hubbard are great generators of the electricity of doing things. They have put into words those innermost emotions which are the instruments of success. They point out a way we may safely follow. They loan us inspiration which causes us to act for ourselves. They give us thoughts that are useful and practical which we never would have gained by virtue of our own reasoning power. 

It is the corniest book ever written but I love it.  I'm probably the most negative guy that ever blogged. I know that I am a nattering nabob of negativity and that people are turned off by that energy. That is why I read Douglas Fairbanks and Dale Carnegie. I, more than most, need to be reminded that reality is what we perceive. Science is not just what we perceive but pointing out how everyone is wrong all the time is a bummer.

Still, some of my favorite books seem to point to fallacy of reasoning. A Drunkards Walk, Wrong, How We Know What Isn't So, On Bullshit and Everything Is Obvious Once You Know the Answer, are just a few of the books that have inspired me to become a more critical thinker and disregard fears of turning people off of my message. Den of Thieves, The Big Short, and 13 Bankers are some of my favorite books on people who succeed while simultaneously driving their industry into the ground. I read biographies like "I Fatty" about the rise and fall of Roscoe "Fatty" Arbuckle. Somehow his tragedy is more interesting than the mundane existence of a biotech guy destined to live an unexamined life. I'm a devout atheist but I don't care to read the latest books on the subject. It is uninteresting because I don't need any reasoning to help me clear up any thoughts on supernatural beings. I read James Randis Flim Flam and I think it's a book that should be mandatory reading at every college in the U.S. He touches on how people believe and why they fight like hell to believe in things they want to believe in, in spite of the facts. I like Malcolm Gladwell even though, as one reader informed me, is a bit of a Cargo Cult social scientist himself. Nonetheless, he has interesting notions and it makes you think. He led me to The Checklist Manifesto. Imagine the complexity of building a skyscraper or running a busy restaurant. Why is biotech so simple and such a failure? I like reading about old Hollywood. Flapper, I Fatty, Minutes of the Last Meeting, Good Night Sweet Prince, Hollywoods Hellfire Club, were all good. These people also led interesting lives and in the end they grew old and came back down to earth. They were human beings that we held up as people we want to be. In examining their lives we get an idea of who we are. Imperfect human beings who have to get up and go to work.

It's clear that I don't read much fiction. Just what I read in the science journals. Wa wa wah! Debbie Downer. What Fairbanks had to say about books is very true. They inspire us and give us thoughts that we wouldn't have on our own. That is what eats at me with modern day science. There are too many intuitive thoughts that need to be proven. Upon examination you find out that those thoughts were too simple. That is when my mind starts to search for explanations. That is also the time I'm sent back into the lab to get the data to fit the preconceived notions. The narratives of the scientists that I've worked for was fiction. Reality is so much more interesting. Without coming to an understanding of the human mind and why we believe such nonsense, why so many people get away with bullshit and rise to the top is hard to fathom. If it's hard to fathom, I'm right there, ready to take notes.

The world is full of diversions that are known to be fiction. Movies, sit coms, and books. Other things are bullshit passed off as reality such as John Edward talking to dead people. I don't mind it because I can avoid it if I don't find it amusing. What I mind is the Flim Flam that has seeped into the world where I go to get away from fiction. I want my reality to be challenging. I want to struggle to understand until one day it all hits me like a ton of bricks and I'm blown away by the amazing world that I live in. I'm not just a negative guy. I'm truly interested in this world and how it works.

The Amgen Study

Why were 47 out of 53 landmark oncology papers studied by Amgen scientists found to be non-reproducible?

Six of the papers, 11.3% were reproducible. The assumption we should all have at this point is that around 90% of published papers are not reproducible. The Amgen study should have expected these results. The recent AACR annual meeting should have contained 90% non-reproducible information.
Each new issue of Nature, Cell and Science should have 90% non-reproducible information. The ten percent that can be used to develop a technology or advance human understanding, is science. The 90% is cargo cult, fraud, bullshit, honest mistakes, accidental or some form of fooling ourselves.

This blog is about both sides, but mostly about studying the 90%. I chose the analogy of Cargo Cults because it requires a religious type of mind to participate in the 90%. I talk about bullshit, in a serious way (ala Harry G. Franfurt, philosophy professor at Princeton), because I believe that is what the leaders are up to. The whole blog boils down to understanding the way in which we participate in non-reproducible "scientific" research and why so many defend the practice.

We begin with a narrative. Ideas get kicked around. A certain percent of those ideas get put to the test in the laboratory. The scientists (creators of the narrative) do not go into the lab and verify the research they are building upon. They do not go into the lab at any point. They send in younger weaker minds to retrieve specific results. Once the data is in it is applied to the narrative and used for writing a paper. Once published the idea must be advanced, preferably by others, to validate the mind (and career) of the person who came up with the idea.

I'd like to recount the journey of one idea and how it landed in the 90% group. It's an old story that I've told in many ways on this blog but it haunts me.

My story is about a small biotech. The company was in existence to sell an antibody against denatured type IV collagen. The mechanism of action was based on an unproven theory, the idea.

A humanized, affinity-matured IgG1 and its parental murine IgM have been shown to specifically bind denatured collagens and thereby inhibit angiogenesis and tumor growth in various animal models. 

The, "and thereby" was the whole idea. As a tumor spreads it tears into the structural matrix of our bodies. Most of that matrix consists of collagen. Therefore, angiogenesis is working on or with the surface of that matrix and its collagen, right where the tumors are spreading. But that was just a nice narrative. They skipped past the science part of proving the theory, made an antibody and swung for a home run.

I participated in several mouse studies where it was proven to me that the antibody did not have an effect on tumor size or growth. When the mouse studies showed no effect on tumor size they simply re-measured. In their minds this was not dishonest. This is precisely the kind of research that the scientists at Amben would have been unable to reproduce. Our initial report to the scientists provided no reduction in tumor size, compared to the PBS group. A paper was later published with a 57% reduction. I'm not sure if they used the re-measured data but it was the same drug on the same mice and tumor cells.

The efficacy of this antibody was presented at AACR in 2006. Also in 2006 Micromet filed an IND.  There is no information on the fate of the antibody. It was last reported on in 2007. My own work on the drug took place in the early 2000s. It was a painful experience. We lost a few good men. Eventually we handed the whole kit and kaboodle over to a group of "scientists" who knew what the narrative needed from the lab.

The people who conducted this research were intelligent people. They knew how to make their presence known in a meeting. They had impressive resumes and advanced science degrees. Their papers were well thought out and they competed well for publication. All of the authors in the 53 landmark studies evaluated by Amgen were of the same breed. Back woods hillbillies wouldn't be able to do what these men and women do. There is a skill involved. There is a culture to fit into. The knowledge of antibody structure, humanization and so on are all complicated concepts that require a certain mental capacity. My bosses had it. The papers and the posters and all of the money are of little value now however. If the goal was ever to put a drug on the market and reduce the size of tumors in cancer patients, they did not have enough intelligence. That intelligence tells you that the truth is the only way to move forward without one day shutting down because you missed something. We were always missing something and we knew it. In the Amgen study, that something was discovered in 47 out of 53 papers. We were always publishing and telling people about things we knew were not reproducible. We were smart and we knew how to avoid having to go back over our work.

What then happened to the research papers from the Amgen study?

The Amgen scientists approached the papers' original authors to discuss findings and sometimes borrowed materials to repeat the experiments. In some cases, those authors required them to sign an agreement that they would not disclose their findings about specific papers. Begley and Ellis were therefore not free to identify the irreproducible papers — a fact that the Comment should have mentioned.

Nature, like most journals, requires authors of research papers to make their data available on request. In this less formal Comment, we chose not to enforce this requirement so that Begley and Ellis could abide by the legal agreements.

The scientists at Amgen could not have implemented their study had they reserved the right to reveal the outcome for individual papers. The Comment highlights important systemic problems in preclinical cancer research, which we felt appropriate to communicate to our readers, even though the authors could not disclose the studies in question.

Bullshit Man!

I'm reading the book "On Bullshit" by Harry G. Franfurt.

That is why she cannot be regarded as lying; for she does not presume that she knows the truth, and therefore she cannot be deliberately promulgating a proposition that she presumes to be false: Her statement is grounded neither in a belief that it is true nor, as a lie must be, in a belief that it is not true. It is just this lack of connection to a concern with truth - this indifference to how things really are - that I regard as of the essence of bullshit.

The business of science fails when they have that lack of connection to a concern with truth. What the many people whom I have highlighted on this blog have taught us is that the truth is not a necessary part of a successful scientific career in academia or industry. Life sciences are most successfully pursued by those with the best bullshitting skills. They do not start off on a journey to find the truth. At the same time they are not deliberately being dishonest. They see the success criteria for a Cargo Cult and they know it is within their skill set to reach the higher ranks.

In the Amgen paper regarding 53 landmark oncology papers we learned that one author published the results of one experiment that was tried 6 times. The author admitted that the reported results made for the best narrative. That was the reason he published his result. This is a lack of connection to a concern with truth.

We've hit some dark times but bullshit remains safely behind the wall of, "It's science".



Would BullshitMan help?

Biology Versus Chemistry

In a recent In The Pipeline post, Derek Lowe asked the question:

Have any of my chemistry colleagues out there noticed the difference in presentation detail between the two disciplines?

The difference between chemistry and biology is blurred in the pharmaceutical business. For example Derek goes on to say:

...most chemists don't (to me) seem to go to the level of detail that I often see from protein purification people...

Let's take a look at a few protein purification job descriptions and their education requirements.

1) BioForce Solutions:  Protein Purification Scientist - BS degree in Biochemisty, Biology, Chemistry, or Chemical Engineering.  
2) Astellas Pharma: Group Leader, Purification Process Development - Ph.D. in a scientific discipline (Biochemistry, Chemical Engineering, or Biochemical Engineering)
3) Sunrise Systems Inc: Research Associate - BS in Chemical Engineering preferred 
4) Laguna Source: Senior Scientist, Protein Purification - Ph.D. in Biochemical Engineering, Chemical Engineering or related Scientific/Engineering field.
5) R&D Partners: Scientist I II, Purification - BS/MS in Biochemistry, Biology or other relevant discipline 


Okay, we've grabbed five random protein purification job listings. They all involve the purification of proteins. Out of the five jobs how many required the following degrees?

Biology     Biochemistry     Chemistry     Chemical Engineering     Biochemical Engineering     Other
2           3                 1             4                       2                            3


In order to address the question that Derek asked we have to first define what a chemist is versus a biologist, in a biotech/pharma setting. According to Derek, chemists are not protein purification people. What the above information shows is that chemists can be protein purification people. 

Have any of my chemistry colleagues out there noticed the difference in presentation detail between the two disciplines?

What if a chemist gets a job as a protein purification method developer? Will he/she present his/her work with less detail than their biologist predecessor?

A trivial detail for sure. It's just a bloggers question to provoke thought. I agree that chemists give less method details but they use too many big words. Ultimately however, details matter. We should worry more about what is not being said.

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.

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