AstraZeneca Destroys Their Airports

AstraZeneca has lost faith in R&D. The rituals have not brought them the cargo they hoped for. The airports are being destroyed.

R&D does not lead to profit. Scientists do not add value to Pharmaceutical companies and they won't be invited back!

Crime on the other hand...

The investment by AstraZeneca in scientists and their laboratories did not pay off. The whole point of this blog is to make the claim that what has taken place throughout the entire industry has largely been a cargo cult science. The scientists and their laboratories have been employing real science, such as the cloning of genes, expressing of proteins, and demonstrating various qualities of the products. But careerism takes over and the science quickly turns cargo cult. As Feynman would say:

they follow all the apparent precepts and forms of scientific investigation, but they're missing something essential. 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.

How do you arrange the good science and technology to get some wealth into the system? AstraZeneca is not giving up on science, just their scientists. Someone else can now do the early stage research and AstraZeneca will take over at a later stage. Their businessmen will make the decisions as to what is good science and they will invest accordingly. The gamble now is whether or not the businessmen will make the right decisions. On the surface it seems reasonable. The expensive laboratories will cease to exist and the entire world of science becomes an open field to explore. Small biotech companies can present their work to the AstraZeneca businessmen and those who are at the proper stage of development will be partnered up. The businessmen know how to arrange partnerships. They know how to attend meetings. Do they know how to spot a scientific endeavor that has wealth built into the system?

Science vs. Scientists

Imagine I am the Csar of Science and I am tired of the culture that places scientists on a pedestal but ignores science. I, as a high ranking government official, have the ability to conduct experiments with 100 NIH funded scientists. There is no hidden agenda here. They are told that it is their ability to uncover the truth that is being studied.

I express a protein in CHO cells. It will be a human antibody against TNF alpha, one of the most popular biotech drug projects. It will be purified to 99% purity and be in PBS. All I tell the labs is that it is a pure protein in PBS. The information that they send back is entirely up to them. What I am looking for is clarity, simplicity, and accuracy. Science shouldn't be any harder than it needs to be. I am looking for a response that identifies human IgG.

This will be stage one. Hopefully they will pay a CRO 500 bucks to perform amino acid sequencing and do a BLAST search. Expense is also a factor in my experiment. Who is the most efficient in simple tasks?

Next I reveal what the protein is. I tell the first 50 to provide physical details such as molecular weight, glycosylation, binding constant... I tell the other 50 to do the same but I throw in that we (the government) want to market the antibody to compete with the others. Once again, I do not tell the scientists exactly what to do. Even the format of the report is up to them.

How does the added information (compete against marketed drugs) affect that reporting on physical properties of the antibody?

Why do I consider this a good science experiment? To begin with, I do not have a bias towards any particular outcome. Next, I have not formatted the scientists thoughts on how to report their findings. We are all blinded as to what the information will be. I am testing the scientists, not the science. I know that the science and technology is available to get the right answers. The known unknown is the antibody. We know what it is. Can the scientists make it a known known? Next is the unknown unknown. I don't know what the group of scientists will do. Will 100% pass step 1 and name that protein? Finally, what affect will the added information (compete against marketed drugs) have on the analysis? Higher binding affinities? Will the government antibody successfully compete against marketed drugs as opposed to simply being fairly compared to them?

My experiment is about bias and science. Are there ways that leaders can prevent bias from affecting science or do the leaders want to bias research? Are there ways of measuring the affects of bias? Here at the CCS we naturally assume that any group of humans will be lead by those most adamant to obtain the desired outcomes. It is science, not scientists, that has no such bias.

Blind Clinical Trials

Last week the Seattle Genetics manager of clinical programming accused of insider trading committed suicide.

One can't help thinking about the leadership of the cults once again. They all seem to know how their trials are going. They design their trials in a manner that allows them to manipulate the data. Dr. Aubrey Blumsohn had this to say about working with a drug company in the analysis of clinical trial data:

It’s hard to encourage anyone to speak out about poor practice in the current environment. This case sums up what has gone wrong with systems set in place to ensure safety and integrity in scientific medicine. It would help if regulators put as much effort into responding to serious critics and whistleblowers as they do producing glossy brochures and yet more guidance.

Dr. Fan committed the crime of using inside information to turn a nice profit for himself and his family. Sam Waksal did the same thing. Aubrey Blumsohn did something a little different. He didn't focus on helping the biotech company tell their story. He tried to tell the story that science would dictate.

What does it mean to have a blinded clinical trial? Who can we trust? Are we blinding the trials to ensure integrity?

When to Retract

Retraction Watch posted a piece on why people/groups retract papers. The reasons people give all point in the direction that what was stated may not be true. What about the papers that are not retracted? Where is the line scientists cross that leads them to correct their mistakes officially?

Previously I've written about the peptide sequence GETRAPL. GETRAPL is the peptide sequence despayed on a contaminating bacteria phage that is found in New England Biolabs phage display kits. If you don't believe me, and you care, you have a few options. A) you can search and search for information on the sequence. B) you can call New England Biolabs and ask them if this is so. C) you can purchase a kit and use it until you start seeing white plaques in the presence of beta galactasidase. You will find GETRAPL!

That is the curious thing about modern science and our near religious faith regarding peer reviewed papers. Rather than going into a lab and reporting your results, people would prefer to find information from others. This is not uncommon. We went to war on faulty CIA information regarding weapons of mass destruction. We didn't retract Colin Powells speech at the U.N. We were wrong, but the war was just. Right? This is akin to the retraction of a paper. We can be wrong but that is not what gets a paper retracted. If you are a scientist who has spent the last 10 years studying the amazing effects of GETRAPL you are not about to retract all of your papers. You would rather just let the subject fade away while you find a way of burying the inaccurate information.

PubMed published an article on a peptide database that came across the GETRAPL confusion.

We suggest that one of the utilities for PepBank is to search the peptide sequences of interest to the user with BLAST or Smith-Waterman algorithms to find any important similarities to the known peptides collected in our database. In this example, the search can be used to remove a relatively nonspecific binder GETRAPL.

Even the last sentence is misleading. The reason GETRAPL ends up on your radar is because the phage displaying the peptide grows faster than the other phage. It has nothing to do with specificity. The sequence has been published and patented and beaten to death by cargo cult scientists. They needed to find something and they did.

So the question is simple: Do they have to retract? The Cargo Cult Scientist studies the ways in which errors occur in the minds of individuals highly educated in the ways of science. Where do they go wrong? Do their peers really get a chance to investigate and add to the story?

GETRAPL is a minor, insignificant story in terms of its impact on curing AIDS or targeting specific cells. It is however a modern day N-Ray story to the Cargo Cult Scientist. After all of the papers about GETRAPL, I have only one conclusion when I see the sequence. The authors used New England Biolabs phage display 7mer kits. That's all I can be sure of. Back in 2009, two years after the PepBank exposed GETRAPL we still have papers like the following:

Recognition of Patterned Molecular Ink with Phage Displayed Peptides
Yue Cui, Anupama Pattabiraman, Bozhena Lisko, Samantha C. Collins, and Michael C. McAlpine*
Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544
Received October 2, 2009; E-mail: mcm@princeton.edu
Published on Web 01/06/2010

An aliquot of phage display library
(New England BioLabs, Ph.D. 7) (Figure 1a) was incubated with
a C8-functionalized Si surface (Figure 1b) and then eluted from
this surface to collect the bound phage (Figure 1c).First, fluorescent characterization for the binding of this phage to
C8 and Si substrates was investigated. This was accomplished by
exposing the substrates sequentially to (1) amplified single-colony

Eureka! I've done it! I've proved that New England Biolab libraries contain GETRAPL.

Education cannot teach people to Google GETRAPL. It is not considered science. Yet it is information. Education cannot teach people to design experiments. It will always be a subjective pursuit. Should Cui et. al. retract "Recognition of Patterned Molecular Ink with Phage Displayed Peptides"? They are wrong. They may have higher degrees in Aeronautical Engineering and work at an Ivy League school, but they have made a mathematical mistake. The data set was too small. The information from other scientists was ignored. They failed to consider alternative explanations. They are wrong. The research, even if correct, wouldn't be all that important. It is the fact that they erroneously attached such significance to their honest mistake that makes it a Cargo Cult Science paper.

Living Up to Our Promise

I've come across a book that acknowledges the lack of productivity from biotechnology. It's called 'Science Business', written by Harvard business professor Gary Pisano.

Why has the biotechnology industry fallen so short of expectations - despite its grand promise?

At the Cargo Cult Scientist world headquarters here in Seattle, we are very excited to hear someone come right out and say this. Earlier this year the leaders of the Seattle Cargo Cults held a conference called, "Biotech is Back". The title was a clear indication that the biotechnology industry does not employ scientific reasoning. The industry continues to suffer from business as usual.

According to Pisano, the problem is the relationship between business and science. Science deals with unknowns. When something becomes known (scientific advancement) we attempt to use it (technological advancement). The scientists know how hard science can be so they chose to become businessmen. They work in offices and adopt business logic. This is where Feynman hopes we do not end up.

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

It's clear that not everyone gets into science because they feel the same passion as Feynman. A degree in BioPhysics will earn you more money than a degree in Theology. When the money started pouring into biotechnology, the wrong people started showing up. They created places where the Feynman version of integrity was not welcome... biotech places.

The book, Science Business, analyzes the industry and its performance over the past 25 years. One of the current assumptions about biotechnology is that smaller biotech firms are better at innovation. Big pharma is tied down with bureaucracy and corporate BS. What they found out in the course of their research was that there was no discernable difference in the R&D productivity of biotech and big pharma. The notion that there is a difference is one that biotechnology is using as a selling point. Executives at big pharma buy into this idea as well, hoping to partner up their next big drug rather than making harder decisions on in house development projects. In the book the author has done the research that those in the industry have ignored. The question was asked, "Who is best at R&D?" The data showed that no one wins.

The book 'Science Business' is on my reading list and I'm sure will generate more posts. We seek to find out why something so promising can turn out like it has. The hypothesis we have is that biotechnology is not doing well. We are not alone.

Retraction Watch, Omeros, and Confounding Factors

Retraction Watch is a scientific gift. Those who value the truth now have a source to help them through the minefield of scientific publications.

Our own blog here, The CCS, follows the retraction of scientific ideas. The ideas manifest themselves as biotech companies. We think of each company as a torch that illuminates a cargo cult airport. The airport I speak of most often is Seattle Biotech since I live here. Our cargo is a drug approval.

Today we report on Omeros. The torch has grown dim.

Omeros (NASDAQ: OMER) said today that its most advanced program in clinical trials, a combination of generic drugs designed to reduce pain and swelling in patients undergoing arthroscopic knee surgery, has failed. There was nothing to sugarcoat here—the drug, OMS103HP, failed to meet its goals in the third and final stage of clinical trials.

Of course we don't just sit back and judge a company based on whether or not they succeed. That is what investors do. We want to know why they failed. Due to the secrecy of modern day science, we don't get the full story. But we do get some hints as to what they think may have gone wrong.

Omeros blamed confounding factors in the studies, which means that if patients improved, it could have been caused by some other reason than the Omeros drug.

Sounds like they made their mistakes before the trials began way back in 2004. Statistics was the problem? How can this be?

The confounding factors in the Omeros clinical trials are what we want to know all about. Omeros is the victim of the confounding factors, and now their investors are as well. We believe that real science can prevent these things from happening. Like Retraction Watch, we believe there is value in negative results. The team at Omeros and their investors are hurting. They took a gamble and lost. Now they are going to put all of the negative behind them and forge ahead. Now is the time however for those in the negative sciences to start their research. If allowed, what would a couple of cub reporters for the Science of Negative Results turn up? The secrecy behind the trial data alone would merit a book. Imagine a series of scientific and business avenues all interlocked that led to the demise of the Omeros lead candidate. Which ones hurt the most? Who made the decisions. Did the molecule really act on its target as advertised? Did the statistical set up of the trials make sense? Many questions could be asked. The answers would serve the industry. Will they be asked? Should they be asked?