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Saturday, March 30, 2013

Replacing the Journal

When we look back, as Feynman did in the CCS speech, we too question the minds of our predecessors. How could the Salem Witch Trials have occurred? It's now considered a cautionary tale on the dangers of isolationism, religious extremism, false accusations and lapses in due process. The Cargo Cults of pharma can be analyzed on each account. They isolate themselves via confidentiality agreements and they don't share raw data with anyone not sympathetic to their cause. They view science as a religion. They rely on, for example, the 51 papers cited in the Amgen study. Even after it is known that 90% of those seminal papers are not reproducible, they keep the faith. Once they have placed their labs atop the bad basic science foundations, they falsely accuse their in-house science staff of being the reason their pipelines are drying up. The due process they practice is to cut and slash jobs. They burn the witches.

In the future we will have better, faster, more intelligent machines and computer software to eliminate the faulty thinking described above. We currently have leaders who do not have to face the cold hard world of the scientific method. I predict a future where the hard copy journals will become more and more obsolete, like the pager or the land line telephone. In their place will be online depictions of the natural world using video (youtube) and words (blogs). Feedback will be immediate and hopefully ongoing. Eliminated will be the isolationism of the chosen leaders and their 'anti-scientific method' peer reviews. By pulling the curtain back on our Wizards of Oz, we will begin to view science in a less religious way. The new process will involve a true community, not a monarchy. I think of a future where truth trumps pretense. Where nonsense from Harvard will take a back seat to the truth from South Dakota State University.

For example, they could examine the latest paper from David Sinclair. Here is where the curtain of Oz is pulled back. The experiments themselves are filmed. Raw data is provided. We are talking about maximizing transparency. What is left to the viewer is only to compare their interpretations with Sinclairs. Imagine each experiment being set up with animations and explanations that your mother would understand. Discuss the system, the cell culture, the method of analysis, the background, the assumptions and so on. Hide nothing. After all, on this webpage you are studying the study, measuring the measurements.

AstraZenecas latest mistake, their partnership with Moderna Therapeutics would be a fun subject to study as well. The foundation of their science is to use mRNA to "trigger production of protein drugs in the body".

They have already provided some video to work with. You provide background, you design experiments, you show the results and allow for an online discussion. Provide a final analysis and leave room for future adjustments. In fact, revisit whenever important information lends credence or detracts from the story. It is, after all, a narrative at this stage. AstraZeneca shelled out money as if they were buying science. They bought a story. 

The time will come when the stories being told will face more and more scrutiny. Retraction Watch was the first to hold up a mirror to the journals and simply let them know that we, the commoners, are watching. We want more than sexy stories. We want tools to build new technologies. Therefore more methods of providing transparency need to become available. I can do without another David Sinclair paper from the journal Science. I can start the countdown to the day AZ pulls the plug on Moderna. What will impact science more than anything is a serious effort to replace the hard copy journals with real time online communications. 

Thursday, March 28, 2013

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.

Tuesday, March 26, 2013


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.

Friday, March 22, 2013

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.

Wednesday, March 20, 2013

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.

Saturday, March 16, 2013

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.

Thursday, March 14, 2013

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?

Sunday, March 03, 2013

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.