Pfizer Demolishes Cargo Cult Airport

AstraZeneca did it in 2011. Now it's Pfizers turn. When the cargo does not come, tear down the airport!

Just take a look at what future generations of archeologists will not find in their search for the ancient research centers. Here

It is a nice little campus. Imagine the butterflies potential employees must have felt walking up the steps to this big pharma research center. This was the big leagues. Good pay, good name on the resume, and a nice location for a cozy east coast waspy lifestyle. Those who were hired did not provide enough value. Some were part of the problem, some were put in an impossible situation. Cargo Cult tribesmen can't bring the cargo by dutifully standing in the watch tower with their coconut headphones.

The fires continue to burn out. This one is a doozy. I'm not convinced of the sincerity of the "bone fide developer" who was going to save the day.

Sources identified the developer as Stu Lichter, president and senior managing partner of California-based Industrial Realty Group, which specializes in bringing empty buildings back to life.

Lichter, in a phone interview Wednesday, said he appreciated the governor and other state officials going to bat for him after he initially approached Pfizer about a deal. He added that Pfizer's decision to back out cost the region at least one major new employer that he had lined up as his first tenant, a bioscience company that would have added between 100 to 200 jobs with an average salary of about $100,000.

A pharmaceutical research site, even after its death, continues to attract bullshitters.

Kumare

I highly recommend the documentary Kumare (Koo-Mar-Aay). In this documentary an Indian man who grew up in New Jersey decides to make himself out to be a spiritual guru. He travels to India to study the mannerisms of gurus and guru followers. He returns to Arizona where he feels no on will recognize him and there will be plenty of would-be followers. He is a fake guru looking for people to believe he is real.



Long ago James Randi ran a similar experiment.



It is this kind of thinking that is at the root of all Cargo Cults. To make people believe in complete nonsense, you need to have a specific skill set. Kumare and Randi demonstrated how it's done. It's interesting how many similarities there are between these two scams and modern/science. Charismatic leaders from exalted institutions convince us that they have life extending elixirs and cancer curing pills.  

Our gurus wear suits and ties, white lab coats when the cameras are on. They have no intention of revealing the scam.  As someone who has friends and family currently dealing with cancer, I think we have to take our guru problem seriously. Let the foolish pharma people continue their quest for wealth. What we have to do is keep thinking, keep asking questions, and keep believing that science is indeed the belief in the ignorance of experts. It's okay not to believe the leaders.

AstraZenecas Solution

AstraZeneca is laying off 5050 human beings. Five thousand and fifty people who came in to work each day to do what they were hired to do, can all stay home now. The board says these people weren't providing value. What can we say about the board?

The board has decided to write a check for $240 million dollars for mRNA drugs. There will now be an unknown amount of human beings showing up to work each day doing what they were hired to do. Their job will be to make the case that Moderna Therapeutics has value.

The AZ board gathered with their investors to discuss their plans for the future. They will be:

Dramatically simplifying the business, improving productivity and building a culture that supports long-term success.

The biggest killer of real science within the industry is the need for scientists to be productive. There needs to be a laboratory of professionals who only provide science. People with job security and long term value. The production of scientific evaluation is different than R&D drug development production. Let the long term scientific lab employees offer up their opinions with no external pressures.

Why will Moderna not bring value to the investors in AZ? Because no one will be testing the validity of this small biotechs claims. No one will question the boards decision to pay $240 million dollars without any scientific verification of the claims made by the biotech company and the due diligence committee at AZ. They will fail. RNA anything will fail. We have zero appreciation of the subtle existence of this nucleic acid and how it is regulated. We think we can improve on DNA and RNA function? Without knowing how it works? We are arrogant and we have to pay the price for our misunderstanding of our limits.

Form a science organization that functions outside of your R&D groups. Let them advise the leadership by using the scientific method to augment the corporate C level executive method. You will find that science is your friend.

Resveratrol, Greek Coffee and Alchemy

Resveratrol was back in the news recently. On a Friday the journal Science published another sexy science paper by David Sinclair. On the following Monday GSK shut down daily operations at Sirtris, a company for which they paid $720 million... to David Sinclair.

The magical elixir, the fountain of youth we call Resveratrol, has found a new rival, boiled Greek coffee. Two can play at that game. It's known as Alchemy. According to Wikipedia:

The defining objectives of alchemy are varied; these include the creation of the fabled philosopher's stone possessing powers including the capability of turning base metals into the noble metals gold or silver, as well as an elixir of life conferring youth and longevity. 

David Sinclair and Dipak Das  have both ran afoul of the research community while pushing the sensational story of Resveratrol. In this paper the technical details the marred Sinclairs narrative are covered. The lab work is really where the science is taking place. The sexy narrative is the specialty of Sinclair and Das. The real science however, is not in the experiments they design to prove their preconceived notions. The real science would be in the analysis of their processes and the verification of their results.

We all want a magic pill. Some of us don't put any thought into such a reality ever coming to fruition, but it would be nice. Some of us still want the promise of Alchemists without the stigma of believing in charlatans and magicians. When people want to take a pot shot at Newton, for example, they bring up his belief in Alchemy. In the cold hard world of business, GSK has put an end to Sirtris. The cargo did not come. The elixir wasn't panning out and they (GSK) had all of the data to confirm their fears. They had been had! The journal Science however keeps the sexy science of Resveratrol alive.

Boiled Greek coffee is the latest offering for a candidate for the magic elixir of life. Here at the Cargo Cult Scientist however, we believe we are witnessing Alchemy in action.

The common thread to longevity is actually known. Smoking, drinking, stress, bad food, bad genetics... These things are going to shorten your life. The pharmaceutical companies will never offer you a "get out of the coffin free card". In the game of life, you have to believe in diet an exercise. It's not so much what certain people put into their body that makes them live longer. It is what they don't put into their bodies. Sadly, we have yet to solve the mystery of making money off of getting people to consume less.

Angry Allozyne

When they shut down the Seattle PI on March 17, 2009 they put an end to a daily telling of the Seattle story. Good people, who were good at their jobs, were let go. It was indeed a sad day for the people and for the art and science of journalism.

The Xconomy came along to take over the news in the tech industry. It reports on how to get money, who is getting money, and why everyone should be giving money to the cargo cults. I don't hide my biases very well. Occasionally however, they do something I like. They let out a secret today about a Cargo Cult known as Allozyne. I ran afoul of one of their supporters last year when I had this to say about their company. I do not understand what these people could be doing in that little space just down the street from the famed floating houses of Seattle.

Thought I'd throw in a picture. It is a beautiful place.

Allozyne started off as a promising story. According to Xconomy, they still are promising.

Seattle-based Allozyne, one of the promising biotech drug developers to graduate from the venture-backed Accelerator, recently conducted a small round of employee furloughs.

They branched off from Accelerator with a fat bank account, fancy digs, pretty people to run the show, and some sexy technology from a couple CalTech brainiacs. They were promising, if you were into appearances. Somehow the rest of the world was not impressed. Since leaving Accelerator, the leadership of Allozyne has boasted of no major collaborations nor any meaningful successes. Enough time has passed to make those of us on the outside wonder what is going on. A news story finally breaks but it is not clear what is going on.

Allozyne made the latest round of reductions to its payroll a little more than a year after another round of job cuts that I reported here in January 2012. CEO Meenu Chhabra Karson said by e-mail, “We did not lay off anyone recently,” but declined to answer further questions. Three other sources close to the situation said staff reductions were made recently at Allozyne and described internally not as “layoffs” but as “furloughs,” which suggests the people affected may be called back. 

Did Meenu deny laying anyone off this time or is that a quote from last year? If her quote is a year old, the only information we have comes from Lukes three other sources close to the situation.  If it's new, why not speak to the rumors of furloughs? We all assume that they will run out of money someday. Are they so Cargo Cult that they don't want anyone to see them without their look of success?

The anger from the Xconomy commenters offers some information. It appears to come from within the walls of that little space down the street from the floating houses. Like this one from "industry exec":

Having worked directly with the company very recently, I've seen absolutely no evidence or impact of the alleged personnel management "reported" here - Allozyne has a solid team and is extremely well led, so hopefully this rather loose and speculative story won't needlessly create noise or disrupt the company's ability to operate and deliver on its technology (which is truly exciting!). I have to say, I seriously doubt the accuracy of this story and would think even Xconomy has a higher journalistic bar for what even qualifies as newsworthy...shame.

Oh, this guy has worked directly with the company very recently... from his office overlooking the houseboats! Then there is this one from JMM:

The Allozyne approach and the products they are generating are top-notch, as is the staff's commitment to their science. If allozyne is refocusing their efforts expect great things from these guys.

Top notch? Expect great things? We've been expecting great things since 2005! To be fair, Amgen took 20 years to really take off but this is not Amgen. Allozyne is a small company that appears to be on its last legs. They took 50M down to 1.1M then managed to put another 4M in the bank last year. 4M is not a lot of money for a company that has to pay Seattle rent, Seattle employee taxes (why not set up shop in Bothell?) and exorbitant salaries to arrogant angry managers. Which one of these commenters was Leroy Hood? Which one was Carl Weissman? Who said this:

we're conducting a paid study with Allozyne and haven't seen or heard any issues either - management team is extremely professional and scientists are hitting our goals. I'd be surprised if this were true.

He calls himself "insider". He doesn't always use capital letters to start his sentences. He must be a high ranking insider exec. He claims to be paying Allozyne. We can no sooner verify his claim than we can verify Lukes. At least we know where Luke works.

I don't have anything to add to the story here. I started the blog a year after Allozyne began. My premise was that most of these little companies were ran on smoke and mirrors. The "entrepreneurs" are mostly PhD or MD level people who have a sense of entitlement. They put millions of dollars in a pot and swish it around to collect what spills over. During the day they hold meetings on how to swish the pot around. When the companies run out of money their work is done. Very few succeed so why worry about the failure. You move on with a C-level pedigree. Good job! Meanwhile the layoffs are real. You just aren't going to hear that from the Cargo Cult leaders.

New Jerseys Plan To Help Biotech/Pharma Workers

Give a man the reputation of an early riser and he can sleep til noon.   - Mark Twain

New Jersey has come up with a plan to offer $14,000 to employers who hire unemployed biotech/pharma workers. The concept here is that New Jersey does not want to lose its highly educated and formerly highly paid people. They enjoyed a period of financial success and they want to keep the gravy train rolling.

The Mark Twain quote above sums up the rather absurd situation. Biotech/pharma had earned a reputation as a successful lucrative industry. Along came the burdens of capitalism. The industry is shedding jobs and the local economy is taking a hit. What remains is the reputation. The local government officials have conspired with the local biotech/pharma executives to force the people of New Jersey to shell out $14,000 every time this failing industry hires a new person.

The $14,000 per person is part of a $3.6 million federal emergency grant, which includes $1 million in on-the-job-training dollars that have to be spent by the September deadline.  

If every dime of the $1 million is spent, about 71 people will land jobs. The workers must have lost their jobs in 2010 or later from various locations of Bristol-Myers Squibb, Hoffmann-La Roche, Johnson & Johnson, Merck/Schering-Plough, and Pfizer.

3400 drug company jobs were lost in New Jersey between 2008 and 2010. The government is going to spend one million dollars to create 71 jobs. Who will get the money? 

The $14,000 grants will underwrite training for six months for up to 50 percent to 90 percent of the employee's salary - although jobs in the pharma sector typically paid much higher than that.

At 50 percent we are looking at an annual salary of 48K. At 90% we are looking at $31K per year. 

The most curious logic in this plan is the training. 

"Every company is going to train their new employees," Flatley said. "This allows us to pay a portion of that training."

What is it about former BMS, Roche, Merck, and Pfizer scientists that lead people to believe they need more education and a $14K dowry? Were they lacking value? Are they still lacking value? Does a Cargo Cult worker have anything to offer the next cult?

Douglas Prasher and Science Careers

One of the most perplexing thought experiments that I engage in here involves employment. You can't experience the joy and the power of science by working in a Cargo Cult. Real scientific thought involves that understanding illustrated in Feynmans CCS speech. You must appreciate Feynmans Wesson oil example. Wesson oil doesn't sink into food as advertised. But neither does any other brand of vegetable oil when applied to food above a certain temperature. A scientific mind will find such marketing tactics disdainful. The disdain towards this kind of dishonesty will lead you into a career in science. You discover that your personality is best suited for utter-bend-over-backwards honesty. Scientific progress will be your revenge on the higher paid marketing execs and the child molesting priests who wish to influence those around you. You have faith that you can succeed by harnessing that power and providing the world with new and better products or services. You've had an epiphany, that science is a way of thinking that leads to things that change our world.

Then comes earning a living in a world that has not had that science epiphany.

It ought to be remembered that there is nothing more difficult to take in hand, more perilous to conduct, or more uncertain in its success, than to take the lead in the introduction of a new order of things.  - Niccolo Machiavelli

In my last post I discussed the career of Gertrude Ellion.

"I would just go ahead and make the compounds, and then the question was, well what do we do with these compounds?" How do we find out if they really do anything?"

She had to take the lead in the introduction of a new order of things. What did that involve? She first had to succeed at making the molecules. She had to provide evidence that she had succeeded. Then she had to find out if they did anything.

That brings me up to modern times and the career of Douglas Prasher. Douglas Prasher cloned GFP. It is a great tool for conducting research. Like Gertrude Ellion, he just went ahead and completed the first step. Gertrude made her compounds through chemistry. Douglas cloned his genes through molecular biology. When it came time to find out what could be done with it, Douglas Prasher had a difficult time. He had envisioned that the gene could be inserted into the end of the hemoglobin gene. When hemoglobin was being made by the cell it would have a green glow. GFP was a small protein that could possible by expressed without disrupting the normal function of the gene into which it was cloned. Unfortunately, he ran out of funding before he could express his GFP clone in the manner he had envisioned.

Since then many others have taken the baton and sprinted on. GFP was a huge success. D. Prasher ended up driving a courtesy shuttle for a car dealership in Huntsville Alabama for $8.50 an hour.  Two of the scientists, Martin Chalfie and Roger Tsien, took the baton sprinted on to win the 2008 Nobel Prize in Chemistry. It's not their fault however that the Nobel committee left D. Prasher out. They were working outside of the Cargo Cult. Dr. Prashers enemies were inside.

Because the innovator has for enemies all those who have done well under the old conditions, and lukewarm defenders in those who may do well under the new. This coolness arises partly from fear of the opponents, who have the laws on their side, and partly from the incredulity of men, who do not readily believe in new things until they have had a long experience of them. 

- Niccolo Machiavelli

The enemies of innovation and lukewarm defenders are the many people one will meet along the way. Pursuing a career in science will not be a success if you only focus on the science. What we set out to accomplish is something new and in direct opposition to the goals of those who have done well under the old ways. Gertrude Ellion and Douglas Prasher both brought about new ways of conducting research. Only one however, succeeded in having a long career in science.  Both scientists had menial occupations mixed in with their science jobs. Gertrude was a secretary and a substitute teacher before taking an unpaid laboratory job. Dr. Prasher drove a shuttle bus. Gertrude is the success story. What did she do differently? It's hard to pinpoint. She lived in a different time and worked under different people. Did she have better Machiavellian skills? Perhaps she didn't need them. Perhaps there is a mixture of interpersonal skills and the need to apply them in your work environment. One thing is for sure, there is more to a successful career in science than simply being a good scientist.

From a Molecule to A Cure

Just to be fair, I want to talk about someone who worked on single target - single drug treatments. This person did her work in a manner that had some "wealth in the system". This was not my experience but I can appreciate that it can be done. I went to a speech given by Gertrude Belle Elion a few years before she died. She won the Nobel Prize in Medicine in 1988. Of all the seminars I attended, this one has stuck with me. At the end of her talk she was asked by one of our professors if she would have benefitted from the modern tools of biotechnology. I can't remember her exact response but her answer was NO! She made it clear that research was something that requires the human mind, not just applying a few technologies. She showed a map of discovery. It went from chemistry to microbiology to biochemistry with stops through physics and math. The process she described was similar to Feynmans view of science. The stuff our professors hoped we had picked up during our education under their watch.

12 December 2008 , published , doi: 10.1098/rsbm.2007.0051 54 2008 Biogr. Mems Fell. R. Soc. 

After receiving her bachelor’s degree in chemistry from 

Hunter College in 1937, Trudy realized that neither she nor her family had enough money for 

her to attend graduate school. She began to look for a job, and immediately ran into the prover- 

bial brick wall. ‘Nobody … took me seriously. They wondered why in the world I wanted to 

be a chemist when no women were doing that. The world was not waiting for me.’ Secretarial 

school followed, and then teaching at a hospital and a high school. She finally landed a posi- 

tion, albeit nonpaying, with a chemist, just to keep busy in her field; during this period she 

decided to pursue her master-of-science degree, which she received in 1941 from New York 

University. During her graduate studies, she started teaching high school chemistry and physics 

as a ‘permanent substitute’ for $7.50 a day. 

Her big break came when the United States entered World War II. Since there were few men 

around, women came to be seen as potential employees, and Trudy was hired as an analytical 

chemist; her job included the measurement of the acidity of pickles and the colour of mayon- 

naise. After a while she tired of those functions and a spell of testing the tensile strength of 

sutures, and sought more meaningful work. The most interesting opening was at Burroughs 

Wellcome, where biochemist George Hitchings (ForMemRS 1974) was trying to make antago- 

nists to nucleic acid derivatives. Hitchings, who would later become a member of the National 

Academy of Sciences, ‘talked about purines and pyrimidines, which I must confess I’d never 

even heard of up to that point, and it was really to attack a whole variety of diseases by interfer- 

ing with DNA synthesis. This sounded very exciting.’ She accepted the position of biochemist 

in 1944 and spent the next 39 years at Burroughs Wellcome, becoming head of the Department 

of Experimental Therapy in 1967. 

Let Trudy explain how she started out making compounds and ended up eventually with the 

first effective drug that induced remission in childhood leukaemia. 

At the beginning … it was my job to find out how to make (compounds). So I’d go to the library, 

look up the old literature to see if I could figure out how to do it. … I would just go ahead and 

make the compounds, and then the question was, well what do we do with these compounds? 

How do we find out if they really do anything?

She attracted many associates who became known as 

a research dream team, some of whom invented azidothymidine (AZT), a mainstay drug for 

treatment of HIV (human immunodeficiency virus) infection. 

Trudy was awarded the Nobel Prize in physiology or medicine in 1988 for her discovery 

of important principles for drug treatment. 

What were those principles for drug treatment? Gertrude and George Hitchens demonstrated differences in nucleic acid metabolism between normal human cells, cancer cells, protozoa, bacteria and virus. On the basis of these differences they developed drugs that blocked nucleic acid synthesis in cancer cells and noxious organisms without damaging the normal human cells.

How does the biotech/pharma industry hire people? How do they use the new buzz word search technology to sort through resumes and end up with someone like Gertrude? Someone who can use the literature to make the molecules AND "find out if they really do anything?"

The executives may be concerned about whether or not they can find these people in the future. Gertrude came from the secretarial pool. She was a substitute high school teacher. Would Gertrude Elion have succeeded, sans PhD as she was, at Pfizer or Merck? What did she have that so many are missing today? What did she and George Hitchens do that the drug developers are not doing today? With all of our modern technology we are missing something. 

Implications of Missing The Complex

The paradigm of the single causative agent - single receptor antagonist, is one possible reality in the quest for new drugs. If so, this is a complicated system. The journey from complicated to complex:

• Complicated, in which the relationship between cause and effect requires analysis or some other form of investigation and/or the application of expert knowledge.
• Complex, in which the relationship between cause and effect can only be perceived in retrospect, but not in advance.

In a clinical trial, we are studying the relationship between cause and effect in retrospect. However, we have blurred the lines between complicated and complex. We begin pharma research by creating a cause, linking protein X to disease state Y. We have reduced our research to a complicated project. We hire experts to conduct the analysis that validates our cause and effect assumption. Our scientists know that their career aspirations lie on providing evidence that the drug intervenes on the cause and alters the effect, the disease. 

Look at health in a different way. Look at it in a complex way. In many disease states, it has been shown that diet and exercise works much better than the pharmaceutical interventions. In the documentary "Forks Over Knives" several very sick people were restored to health. The intervention was not simply that protein X causes disease Y. Some combination of the wrong food at the wrong quantities was causing a disease state. Changing diet and exercise habits brought about real change. But what was the cause, on the molecular level? A single target protein that was attacked by a barrage of vegetables? 

Let's replace the Forks Over Knives success stories with the curse of baldness. Have we ever changed a diet and exercise routine to reverse baldness? If we had, men all over the world would make the change. They do it to sculpt their bodies. Why wouldn't they take the advice seriously to stop losing their hair? What is it then that prevents people and scientists from learning more about the complexity of the human body and the relationship to diet and exercise? Is is because it is too hard, too complex? The madness of Resveratrol comes to mind. Someone noticed that the French had longer life spans than the rest of Europe. They focused in on red wine. They wanted to find one single molecule that they could make into a pill. A few years later Resveratrol. N-Rays in a capsule. Once again, a single agent that provides a key to long life. But it didn't work. 

So we really ought to look into theories that don't work, and
science that isn't science.

Covx, The Cult of Barbas

The last posts title was, 150,000 Jobs Lost Since 2009. Add another 100 or so losses from the ranks of Pfizer. Covx is going away. Started in 2002, Covx used phage display to make peptide-antibodies. Improving on natures invention of the antibody, Covx selected peptides that bound to target proteins (like an antibody) then they attached the peptides to a stealth antibody. The antibody protein is there only to stabilize the peptide and increase its bioavailability.

No one will talk about the demise of Covx like the Cargo Cult Scientist. The question we have is, and always has been, regarding the sustainability of the single target - single drug paradigm. We humans have thrown billions and billions into the paradigm and we haven't come up with much. Humans can still get rich in our current health/sick care system investing in this drug development approach. But are we really making any progress in treating disease? Do we understand how one protein can make us sick? How does one protein spin out of control, unregulated by the controls built into our DNA over billions of years, then suddenly become properly regulated by a single molecule that humans design in a few years tested at a few dosages? It seems highly unlikely that this actually works.

The CCS once worked with the laboratory that spun out Covx. Their phage displayed antibodies were sent to us in vials of various consistencies of goop. Our job was to take the goop and run western blots to verify binding to our target. Down in San Diego that merely had their technicians select candidate based on an arbitrarily selected ELISA signal. Anything above X was sent up to us at UCSF. Every single ding blasted frigg'n candidate was selected due to high background. We learned that they were panning their phage against completely denatured proteins. No structure! The day they started using non-denatured proteins to pan against was the day they started getting actual target binding antibodies. Those of us running the western blots were put through a humiliating few months of heavy criticism on our western blot skills.

Covx however was no different than most. They begin with the single target - single drug molecule paradigm. They have a technology to obtain the single drug molecule. A technology is a practical application of a science. That technology was not theirs originally. Phage display was developed by Dr.
George P. Smith at the University of Missouri. The folks at Scripps got ahold of a sexy new technology and ran with it. They made the Herculean leap from phage display technology to medical science. My personal knowledge that comes from experience indicated to me that they were lacking wealth in their technology system. How might they fare in the upper realms of science?

How can a group like this go on to form a multi-million dollar partnership? Some say the founder was awarded a couple hundred million dollars from Pfizer. Well of course the founder and a few at the top were the winners. The laboratory people are the ones who are suppose to  add those pesky details like having an actual test for target interactions. The leaders offer up the sexy narrative that attracts the investments. In our case, we were attracted to them by the narrative of getting antibodies quickly and for less money. In the end, we received ordinary antibodies that anyone with phage display skills could have provided. Ordinary...

Was Covx an ordinary phage display group that had an influential leader, Carlos Barbas, who excelled at the narrative? According to Pfizer, upon the acquisition of Covx:

CovX’s biotherapeutic platform is a technology that links therapeutic peptides to an antibody“scaffold”. The peptide targets the disease while the antibody scaffold allows the peptide to remain in the body long enough to achieve therapeutic benefit. The technology thereby allows half-life extension and bioavailability to support optimal dosing regimens for peptide therapeutics.

As validation of this technology, CovX has generated three early- stage compounds, one diabetes and two oncology compounds, that are expected to further strengthen Pfizer’s biologic pipeline portfolio.

Is it fair to say then, that "as validation" that this technology is just phage display, smoke and mirrors, Pfizer is sacking the entire staff of Covx? 

"We are pleased to transition the CovX technology to Pfizer's Biotherapeutic and Bioinnovation group and are confident they have the vision and resources to scale the platform and realize the opportunity to make efficacious drugs which will make a difference in peoples' lives," stated Shehan Dissanayake, Chairman of CovX and CEO of Tavistock Life Sciences.

I talked about a former gambler who decided it would be best to sell his picks rather than bet on them. For a fee he would let the gambler in on who he thought would be covering the spread that day. In a sense this is what Jeff Kindler and Corey Goodman did back in 2007 when they acquired Covx:

“The acquisition of CovX is a further step in Pfizer’s strategy to acquire and identify new product candidates that we can put into development, leveraging both Pfizer’s expertise and that of world-class scientists charged with discovering and bringing in new compounds,” said Jeffrey Kindler, chairman and chief executive officer of Pfizer. “With this deal, we are building on our recent announcement of a new Biotherapeutic and Bioinnovation Center based in California and led by Dr. Corey Goodman. We are looking for the best science wherever we can find it, with a special focus in our priority areas, such as biotherapeutics.”

 The ceremonial beginnings of Cargo Cult projects are always followed up by the rather unceremonious  announcement of their demise. It is sad to see so many people out of work. But we have to wonder if they were actually doing work, or were they focusing on the narrative offered by their leadership.

My friends you are getting tired of hearing it from me, but the cargo didn't come. Covx did not fail because the guys with the white lab coats were no good at phage display. They failed because the narrative was cargo cult. Phage display is real. We can select peptides that bind to targets. We can't make the binding lead to the outcomes described in the narratives.

Farewell Covx. Good luck to those who invested years of their professional lives on the Covx promise.

150,000 Jobs Lost Since 2009

According to PricewaterhouseCoopers, 51% of pharmaceutical execs are of the opinion that it's getting harder to find good help. As reported by Pharmalot:

...a slight majority of drugmakers complain that it has become increasingly difficult to find the right talent and most worry they will not have access to the people they need to hire.

If this abstract group of humans, the pharma executives, has such a good idea of who the right people are, why did they hire all of the wrong people in the last couple of decades?

Since we think that the Cargo Cult mentality is the hidden story behind this industry, we find the question of finding talent interesting for other reasons. The question we ponder is about the actual research conducted by PricewaterhouseCooper and the innumeracy that goes into considering the validity of their work.

Driving home this evening I heard an ad from a Las Vegas odds maker. If you want to gamble and win, you give him some money and he will let you in on a few sure bets. Of course, if you take his advice and lose, the money you bet plus the money you paid the expert is all gone. No refunds. Knowing the odds is what gambling is all about. Once you figure out how tough it is to make a living gambling you might just want to turn to a safer bet. Rather than laying down your own money on the Superbowl, have people give you money for your pick. Genius! Don't be the gambler.

That is what we have here with the PricewaterhouseCooper research team. They serve as the expert selling the unknown knowledge hidden to the common man. The bias we may all have, that massive layoffs lead to talent shortages is not even being quantitated. The experts in judging an industry merely asked the experts who run the industry for their opinion. Even if difficulty is encountered when hiring the talent, it could just be that the experts are not good at identifying talent. Simply because the executives feel uncomfortable is no indication that talent does not exist?  It's just a feeling, like our gambling friends feelings about the Lakers chances over the Bulls next week.

What was lost in the course of laying off 150,000 people since 2009. Only the executives know. They are like the seller of gambling secrets. They know something you don't. At least, that is what they are selling.

Did you know that the word gullible can't be found in the dictionary?

What are the odds that the pharma experts in this research know what they are doing? They have yet to come up with anything as powerful as a proper diet and daily exercise. They attack single targets with the usual suspects; small molecules, antibodies, RNAi... and they want us to believe that clinical data is solid. Just don't ask for the raw data. The industry has been propped up by the occasional useful product. Antibiotics, Insulin, the Polio vaccine are the kinds of breakthroughs we wish for. Drug products like Provenge are what we seem to get. It appears that the talent they seek is in finding people who are best at hammering square pegs through round holes. The status quo has a track record of not being able to predict the breakthroughs. Without predictable success in our pipelines, we select for corporate types who succeed where more honest types accept defeat. As a result, chances are we'll lose more jobs. Some of the jobs may just be currently held by someone who offered up their expert opinions to PWC.

51 percent of life science execs – which is the highest of 19 sectors examined – say that hiring is getting tough and only 28 percent are confident about finding the right candidates. This comes as roughly 60 percent of pharma execs plan to invest more heavily over the next three years to create a more skilled workforce and 72 percent intend to boost their R&D capacity over the next 12 months, PwC Health Research Institute reports.

The ex-gambler who now sells his knowledge is an expert. He knows the odds and the futility of placing the bets. He makes the picks, sells them, and lets the gamblers lose. Perhaps the biotech/pharma industry, after sacking 150,000 people, has become concentrated with similar experts. They know where the risks lie in a career path in the industry. In spite of all of the losses, they are still there selling their knowledge. Quantitating that knowledge is most likely not going to provide any insight on the future in the drug industry.

A Great Rant

I tend to enjoy what some refer to as "rants". I think this spirited dialogue posted on the "In the Pipeline" blog yesterday was most enjoyable.

I’m leaving bioinformatics to go work at a software company with more technically ept people and for a lot more money. This seems like an opportune time to set forth my accumulated wisdom and thoughts on bioinformatics.

My attitude towards the subject after all my work in it can probably be best summarized thus: “Fuck you, bioinformatics. Eat shit and die.”

 One commenter had this to say:

When someone finds fault with the way a field conducts itself, I would implore them to constructively influence that field. You might be surprised how many are actually sympathetic to your concerns. 

I'm not dismissing this author's concerns: to do that would really require knowing the molecular biology field (which is more than sequencing, it turns out). I do neuroscience right now, and programming can be a problem for some. But a constructive suggestion to change can have much more impact than a long rant.

This "long rant" was chock full of interesting ideas. The human genome project was not a science project, for example. Good science require an understanding of the limitations of ones tools. That is good stuff. This was a rant, devoid of mitigated speech. Notice how quickly the lack of mitigated speech became the topic of discussion for the commenter. He did not dismiss the author's concerns, nor did he have anything constructive to say about those concerns. What was at issue for the commenter was the rant.

Here at the CCS we feel that the rant was fun. It was real, written with obvious passion, and spot on. We too spent a short period of time at a bioinformatics company called Protein Pathways. Garbage in, garbage out. Our competitor, Rosetta, beat us to a buy-out from Merck. Neither Rosetta nor Protein Pathways are in business today. The cargo never came.

If you were an investor, you could easily discard such rants, my entire blog included. To some, we are not offering constructive criticisms. But read with a critical eye, vitriol in italics, big picture idea underlined.

All the molecular biologists, devoid of skills beyond those of a laboratory technician, cried out for the mathematicians and programmers to magically extract science from their mountain of shitty results.

The big picture idea here is straight out of the Cargo Cult Science speech from Feynman:

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.

"extract science from their mountain of shitty results"

"get some wealth in their system"

This is what it is all about. This blog and the numerous rants all focus on this area. Sure we are angry. We want to explain, using our education and experience at your Cargo Cults, what you are missing. We want to point out why there is no wealth in your system, nor your investors bank accounts. But it is as difficult as explaining to the South Sea Islanders how to arrange things.

Good job Fred Ross. You are an official ex-tribesman of the Cargo Cults of Biotechnology.

Research Degree

College degrees come in levels; BS, MS, PhD. A university may have a liberal arts college, natural science college, engineering and so on. In each degree program the university will require the students to have a certain amount of credits from other colleges, to ensure a well rounded education. This is very important. The ability to communicate both in written and oral presentations is important. It may have little to do with learning about how a protein is translated but communication is a part of any professional life. Beyond communication, a career in research should require more.

If you want to become a high school chemistry teacher you need to learn how to teach. You earn chemistry degree and you get a teaching certificate. If you want to conduct research for a biotechnology company or the pharmaceutical industry... you have chosen the path of least resistance. You get your degree; BS, MS, or PhD, and you start looking for work. Your college professors were most likely researchers. They are looking for cheap labor. Research grants bring in lots of money for our modern universities. As a result the natural selection of tenured professors has created an emphasis on research ability as opposed to teaching ability. That means that lessons in writing grant proposals are seen as more important than a course in logic over at the Philosophy department. Over time we have watered down the scientific skills needed to conduct research. Human constructs such as grants and publications become our biggest challenge. When it comes time to apply what we have learned, to take a job, many will simply become middle managers. What they have is an understanding of how to please a superior.

In science, nature should be our boss. That means that we need to learn how to conduct research. If you chose to become a middle manager, perhaps you need only a BS and a middle management certificate. If you chose to work in business development, you will need a different set of skills. The most difficult career path to actually succeed in however, is in research. Nature does not reveal its secrets without a fight. You must learn how to fight.

Under the current system, those who work on the front lines in the laboratories show up to the fight with just a BS. Perhaps here is where we insert a research certification. BS, MS, PhD indeed, but what is the certification? Are you on a chosen career path or has your lack of ambition got you stuck in the lab?

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.