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Friday, October 29, 2010

Empty Buildings

So up to 90 percent of medical science reports could be B.S. One of the consequences is of course that your doctor could be following a cargo cult science when he/she tells you to take your pills. But we like to look at the airport as well.

Here in Seattle we had a push to start up a biotech hub. We wanted to compete with Boston and North Carolina and San Diego and the bay area. We built expensive buildings with lots of lab space to accommodate that science that is 90% false. How did it pay off?

Empty promises bring empty buildings. Contrast our biotechnology investment with the investment in politicians. 3.7 billion! Giving politicians money produces desired results. Maybe you want the government to add an earmark to a bill that will provide you with the money you need to create a Laurance Welk museum. It's been done. You can't pay a politician to cure cancer. Nor can you expect a biotech to do it. It hasn't been done.

Imagine taking a walk today through the empty spaces available for biotech. The smell of new construction, the lights turned off, no people around, and you keep walking for miles. What happened? 1100 Eastlake was completed in early 2009 — "just around the time the world fell apart," Blume said. The world didn't just fall apart in 2009. Biotech has been falling apart since it began. The success of a few companies fooled investors into thinking easy money was to be made. But the data of failed companies as a direct result of bad science has escaped the wealthy. Their starting to come around to the truth. It's a cargo cult airport!

Thursday, October 28, 2010

Meta Analysis, Measuring Measurments

In the early chapters of Dr. Ben Goldacres "Bad Science" he begins to unfold the concept of meta analysis. In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. Simply follow this link, and type meta analysis into the search box. I know I'm being lazy but no one says it better than Bad Science.

Bad science can be done in a clinical trial ran by a homeopathy company or a big pharma company. Both groups can work around almost any set of data. They practice an advanced form a cherry picking statistical analysis that is hard to detect. Meta analysis however has a way of measuring the measurements of clinical trials. In essence, it is a clinical trial of the scientific reasoning behind a particular area of interest.

Bring in Dr. Ionnidis (YO NEE DEES). In the November issue of The Atlantic David H. Freedman has an article titled "Lies, Damned Lies, and Medical Science". The main character is Dr. Ionnidis. He is a meta-researcher and he's one of the world's foremost experts on the credibility of medical research. Alas the CCS is just a lowly blogger but this guy has introduced science into the equation.

Dr. Ionnidis: "There is an intellectual conflict of interest that pressures researchers to find whatever it is that is most likely to get them funded".


Dr. Ionnidis sees a pattern (the as does the CCS) and he has a method of testing his hypothesis. Of course this means that he has his own bias. As they point out in the article, it would not be very interesting if he did the analysis and found that most clinical trials are more or less correct. Dr. Ionnidis claims that roughly 90% of the medical research that doctors rely on is flawed. By merely pointing out the bias however, he has risen above the norm.

Making a Drug Follow-up

Biospace reports a few snafus in the manufacturing side of big pharma.

Sandoz Pharmaceuticals Initiates Voluntary Recall of Ceplene in the US

B. Braun Medical Ltd. Voluntarily Recalls Seven Lots of Heparin Manufactured in 2008 Due to Supplier-Initiated Recall of Heparin Active Pharmaceutical Ingredient (API)

Crucell N.V. (CRXL) Halts Vaccine Shipments to Investigate Plant

This is not a cargo cult issue. It is quite the opposite. The reason for reporting errors and removing drug product from the market could be due to a moral issue of not wanting to hurt anyone or a business decision that makes the potential downside too high of a risk to take. Either way, the best thing to do was to remove the product from the patient.

This adds to yesterdays post on drug discovery vs drug manufacturing. Discovery is riddled with Cargo Cult Science. Manufacturing however must be done in a manner where predictable outcomes are an absolute requirement. When you have a problem you cannot hide it. Discovery is a whole different world.

Wednesday, October 27, 2010

Drug Development vs Making a Drug

How does a small company move from drug discovery to drug development? The answer is in partnering with people who know what to do. A handful of PHds from MIT who start up a biotech company based on some clever cloning vector do not have the proper experience to begin developing upstream and downstream processes that can be scaled to a GMP facility. They must seek help. This is difficult for any PHd.

What is happening to biotechnology today is similar to what happened during the dot com era. Initially people were very excited and money was not hard to find. After too many empty promises the money has dried up. Investors are looking for more advanced programs. In biotech that means they want a drug in phase II or III. In order to get there you have to have a drug to put into people. How do you do that? Biotech start ups only know how to get to the drug discovery phase. After this they must either outsource or learn new skills. The former is more desirable.

Big Pharma wants the little guys technology. Like the zillions of little companies that went out of business in the last 20 years, big pharma has also had a tough time discovering new drugs. They must look outside of their organization. They look to people who most often have never actually made a drug, small biotechs. They don't know the rules and there are lots of them. Still, big pharma and biotech partner up and roll the dice.

One group that doesn't gamble in this process are the contract manufacturing organizations. They accept the job, develop the methods and produce the drug. No further research will be required.

Does biotech understand the bottleneck of manufacturing? Do they understand clinical trials? That is another story. Once again, we clump the companies into a population. Some are better than others. Some are great at science but horrible at engineering issues. But go to a biotech company website and seek out the information that touts their ability to perform necessary routine development work. It's just not sexy. Without that expertise however, they won't even know who to call to get help. If you want money, you have to get smarter. There is now a new question start ups must answer besides "do you have a drug"? "Can you make it"?

Saturday, October 23, 2010

Wiki Leaks Didn't Write the Documents!

Those in power often times work in secret. Those outside of the chosen circle can't handle the truth.

But the truth is a powerful force for good. The story about WikiLeaks release of Afghanistan and Iraq war documents has angered those in power. The truth can get you in trouble. But the truth is the truth. In the long run, the truth is your friend.

"In our release of these 400,000 documents about the Iraq war," WikiLeaks Founder Julian Assange said, "the intimate detail of that war from the U.S. perspective, we hope to correct some of that attack on the truth that occurred before the war, during the war and which has continued on since the war officially concluded."

What the mainstream media is ignoring is the organizations use of the truth to fight the notion that war is necessary. Science uses the same tactic. The truth is what is missing in cargo cults. It is replaced with ceremonial practices. If Wiki Leaks is in fact jeopardizing our security, where is the evidence? Why do Hillary Clinton and all of the other powerful people in our Cargo Cult claim that this will hurt us?

The Cargo Cult Scientist believes that war is a ceremony performed by group leaders to establish superiority over each other. It achieves very little and it destroys too much. Yet it has been established as a way of dealing with difficult outsiders. Does it work? Is it worth the guaranteed destruction of life and property? By looking at the reality of a war we can ask those who order the ceremony to account for it. We the little people do the ceremony. We look to the sky. Did the airplanes come?

Friday, October 22, 2010

Financial Crisis Adjustments

Having to sell a house at this time has taught the CCS a painful lesson. Nothing is impossible. A house once worth 200K more than it was paid for (in 1.5 years) is now selling for 5K less than the original price. And it's not selling!

A few years ago the house would have sold faster and for much more. Same house, different time. In the Yahoo news today the story is that Dubia real estate woes have sent the rent in the worlds tallest building to approximately 60% of what they went for last year. So who is in charge of determining value?

If you are a real estate agent and you made 300K per year between 2003 and 2006 is your job not harder now that houses are harder to sell? Same person, more difficult job, lower pay. You were overpaid (over-valued) and this is an adjustment.

The upper echelon must learn that they are like overpriced real estate. The value they placed on themselves needs to be adjusted. In essence, they are like the top penthouse apartments. Their children, getting advanced degrees in the finer universities, are like new construction that will soon dilute the money pool of executive pay.

The goal is to make the adjustment without destroying as many people as did the real estate market. Place more value back on making a product or providing a service.

Thursday, October 21, 2010

Biotech Logic and Initiative 1098

How hard is it to attract the right people to your cargo cult airport? Cargo cult airport technicians are people of great logic. Whether they work in the watch tower with coconuts over their ears with sticks for antennas, or whether they wrap a wire around their body and serve as a radio, they don't want to pay taxes.

So says the CEO of Dendreon.

Dendreon CEO Mitchell Gold says more is to come. "My goal is to build a fully integrated biotech company in Seattle," he says. The company envisions a campus of buildings that would include a pilot manufacturing plant.

This, to remind you, is for a drug treatment that costs 93K for one round. Mostly well to do cancer patients will be treated. Poor folks will mercifully die sooner.

Back to the article:

"And that requires the hiring of top talent from around the United States, says Rich Ranieri, the company's head of human resources. The need is for scientific talent and also commercial talent specific to biotechnology — a talent pool that has not existed in Seattle since the sale of Immunex in 2002. And that means recruiting men and women from the big biotech centers in Massachusetts, New Jersey and California.

Some people in those states jump at the chance to move to Seattle, but many do not. This is not the center of their universe. A recruiter needs enticements — and one of ours is no state income tax.

"Having no state income tax is an attractive tool for us," says Ranieri. "It matters."

For this city, biotech matters. It is part of our future. Let's not mess it up Initiative 1098."

The gist of the initiative is that people earning over 400K year will have to pay an income tax.

My favorite comment from the online responses:

"Dendreon hopes to make its money selling $93,000
treatments for doctors to prescribe to old rapidly dying men for a 4 month survival "benefit". Who will pay the $93000 to Dendreon? Mainly taxpayers paying into the Medicare system.
Who does the money go to? A CO. w/ management that wants its taxes lowered!
What a country!"


Tuesday, October 19, 2010

Airport Authority Discussion

It's gonna turn this whole thing around.

Of course our airport is in trouble. The investors gave generously, the cargo cult workers did what they thought would bring the metal birds, nothing happened, big pharma gave up hope, investors got tired of losing money, workers were laid off, and now it's October of 2010.

But it was not a lost decade. When you practice a biotech kind of science you can expect 99% failure with a lucky win from time to time.

What if there was a forum with the losers? What about the workers who knew about the mistakes that were made? What if there was a poster session of the most comical scientific logic displayed by local biotech leaders? To put it all in proper perspective there should be a counter forum to "Biotechs Back in Seattle".

Someone should put together the stats of jobs lost and jobs gained in the past year. How much money was poured into the existing companies and how many jobs did it create. What kinds of jobs are now in demand? What is biotech and how is it back?

The panel are people who need to attract money to the area. Should we trust what they are saying?

Monday, October 18, 2010

Top Ten of 2010

President Obama has put together a top ten list. They call it the National Medal of Science Laureates.

Stan Prusiner, Nobel Prize winner 1997, made the list. But what has he done since winning the prize? What did he do before he won the prize?

The key to winning awards however is to silence your enemies. As a brilliant politician, Prusiner has earned many awards. But it is Taubes who has fought a brave fight against the arrogance of scientific authority. He didn't care who was right, but what was right.

Sunday, October 17, 2010


"Interestingly, mutations were observed at a frequency dependent on display valency".

This is a quote from a paper that was published regarding some work that I performed. It is a confusing statement. A phage library was made with 7 random amino acids stuffed into a 20 amino acid peptide. Does the statement mean if there were 8 random amino acids that there would be more mutations?

Like Feynman said, we should report everything we do, not just the things we want people to believe. Phage libraries can be made from simple oligo sythesis samples from companies like Invitrogen. There were ten vials of DNA preparations that came from several oligo orders from Invitrogen. One of the oligo orders came in with all phenylalalines where random nucleotides were suppose to be. Not a mutation, but a mistake at Invitrogen. There was one oligo that gave the best results. It was used to make 5 DNA preps that were inserted into our phage vector. Only 2 of these preps gave the results we needed to get the library done. 90% of the library come from the first prep.

The other oligos should have been the same but we humans were doing work with them. The "mutations" that the paper mentioned disappeared when a new oligo was ordered. However, new "mutations" came with new DNA. It is a normal occurrence in cloning man made DNA into vectors. The fidelity of the DNA insert was pretty good actually. The only thing interesting is how ignorant the authors of the paper and the editors of the journal were to this fact.

Perhaps someone else should have tried to reproduce the work. That would serve everyone interested by demonstrating that the papers "mutations" claim was not only wrong, but a non-science claim.

Friday, October 15, 2010

Scientific Satus Quo

Bad times have a scientific value. These are occasions a good learner would not miss.
Ralph Waldo Emerson

The best experiments have built in controls to help you believe the results. If you want to quantitate a protein, for example, besides an unknown there should always be a known. It should incorporate numerous measurements so that statistical analysis can be applied. What might happen is that your known shows a lack of precision and/or accuracy. Then you have some information about the measurements of your unknown.

Since the CCS is a biotech worker, we have often seen a standard curve of 5 data points, each measured once, and an unknown measured once. Even worse, we have seen the standard curve imported from a previous day. The unknown is measure once and that is all. Now would this be important information? Scientifically, yes. Would the CSO of the company waste his important time on such trivial details? No. But isn't this the part of the business that matters most? Whoever has power within an organization doesn't have to focus on every detail. But they should serve as the judge over whether or not rigorous scientific experimentation is taking place. This is how junior personnel pull the wool over the eyes of people like Dr. Woo and Baltimore who want specific results and aren't paying attention to how they are obtained.

So I go back to the concept of the Misconduct Journal. Each act of misconduct is a gem that can be used as a learning experience for everyone who works in science. And each monthly issue will have a fresh new case to explore! There are no shortages of those who get caught. Imagine the actual number of cases that should be reported.

Again... Feynman: "One example of the principle is this: If you’ve made up your mind to test a theory, or you want to explain some idea, you should always decide to publish it whichever way it comes out. If we only publish results of a certain kind, we can make the argument look good. We must publish both kinds of results".

The entire scientific community seems to be focused on positive results by top notch scientists. What about top notch science by human beings. Anyone can do it. A scientific journal should be able to focus on science.

Thursday, October 14, 2010

Woo Retractions

Gene Therapy is interesting. There is something to confusing a cell with extra DNA. We know we can insert DNA into a genome and it will express a protein of our desire. It may also splice that piece of DNA out of the genome.

But to simply throw DNA at a cell is not science. You randomly introduce DNA to a living organism, see what happens and create a story behind the results. So far there hasn't been the kind of explanation of gene therapy that leads to a predictable outcome. Throwing dice on the other hand has been studied for centuries and we know what will happen.

Which leads to the Woo story. Two of Woo’s post-doctoral fellows at Mount Sinai School of Medicine were dismissed for “research misconduct,” said Ian Michaels, a spokesman for the institution. According to Michaels:

"When Dr. Savio L C Woo came to suspect that two post-doctoral fellows in his laboratory may have engaged in research misconduct he notified the Mount Sinai Research Integrity Office. Mount Sinai immediately initiated institutional reviews that resulted in both post-doctoral fellows being dismissed for research misconduct. At no time were there allegations that Dr. Woo had engaged in research misconduct. As part of its review, the investigation committee looked into this possibility and confirmed that no research misconduct could be attributed to Dr. Woo, who voluntarily retracted the papers regarding the research in question. Mount Sinai reported the results of its investigations to the appropriate government agencies and continues to cooperate with them as part of its commitment to adhere to the highest standards for research integrity".

The papers, which appeared in the Proceedings of the National Academy of Sciences, the Journal of the National Cancer Institute and Human Gene Therapy, involve findings published between 2005 and 2009, address various aspect of gene therapy. Two of the articles boasted of potential breakthroughs, and even a possible cure, for diseases with extremely high rates of mortality.

No there was no misconduct on Dr. Woos' part. Just an eagerness to see what he wanted to see. And that is a Cargo Cult offense.

Saturday, October 09, 2010

Mercks Big Bet Revisited

Long ago I just knew that Mercks acquisition of Rosetta (bioinformatics) and SIRNA (RNA silencing) was a match made in the imaginary heaven that exists in the hollowed heads of BigPharma/Biotech executives.

See Mercks Big Bet, 2006.

Since then I've updated the blog to point out the closing down of Rosetta. Merck has been pretty tight lipped about the progress they've made in the four years since so I've nothing new to report.

There remains Marina Biotech, Tekmira, and Avi Biopharma in our Seattle Cargo Cult Airport.

We are still following the RNAi story and there still is a story. That is astonishing to me, the CCS. Somewhere out there, grown up men and women are still convinced that RNAi is going to become a drug. Why do they think that?

Tuesday, October 05, 2010

When Credentials Outweigh Capabilities

Usually, credentials. evidence of authority, status, rights, entitlement to privileges, or the like, usually in written form: Only those with the proper credentials are admitted.
anything that provides the basis for confidence, belief, credit, etc.

Usually, capabilities. qualities, abilities, features, etc., that can be used or developed; potential: Though dilapidated, the house has great capabilities.

I was talking to a person in the human resources side of biotechnology. He tells me that pHDs are removing the pHD from their resumes. Has the industry started to sour on the title? It used to say, "I'm capable". What does it say now?

Sunday, October 03, 2010

The waiting is the hardest part

Can You Blow the Whistle on Bullshit?

In the Baltimore Case, Margot O'Toole, found she was unable to reproduce some of the reported results in her own experimental mice. Her attempts to resolve the problem with her immediate boss, Dr. Thereza Imanishi-Kari, led O'Toole to suspect defects or errors in the original research. Her doubts seemed to be confirmed when inspection of laboratory notebooks revealed discrepancies with the published results. Apparently fobbed off by Imanishi-Kari, with whom there was obviously a major personality clash, O'Toole felt affronted that her superiors appeared to show so little commitment to the fearless pursuit of scientific truth to which they paid lip service. She made her suspicions public and turned whistle-blower.

If you are gay, over 40, female, of a minority race or in some other protected class, there are laws that prevent you from the harassment Margot O'Toole experienced. Margot O'Tool left the biological sciences for many years after blowing the whistle on Baltimore and Imanishi-Kari.

What if there was a court of law that would hear your case against scientific bullshit. By bullshit I mean anywhere from honestly mistaken to fraud. The only issue of the court would be the truth. Credentials would not be allowed. The protected class would be those who are speaking the truth.

The Buy-Out

Zymogenetics has operated in Seattle since 1981. They even made a few products along the way. Their fire along our runway however will soon be extinguished. One of Zymos eulogies discussed the health of the biotech industry in Seattle.

"Biotech advances flow from the well of scientific discovery. Individuals who haven’t worked in a biotech setting don’t always grasp the synergistic benefits of putting together a research team that recombines individual talents to innovate fantastic discoveries that lead to new drugs."

He goes on to point out, "A quick look at the WaBio website shows only about 33 job openings at local biotech companies, with about an equal number of jobs listed for academic and other institutions. Since 2002, when Amgen bought Immunex, there have been over 3,200 layoffs at local biotech companies (not including any upcoming layoffs at ZymoGenetics or Trubion), and I would wager that a lot of these folks were unable to find employment locally."

That is 3200 gone and 33 still available. The only piece missing here is how many jobs have opened up since 2002? That is the health of the industry and its ability to keep the college educated work force required for research teams.

I found a comment from another article regarding demise of Zymo: "I’ve been in pharma work since ‘93, and with Seattle-area biotechs since ‘97 and I’ve been through three layoffs, five mergers and and two company failings.

I had a co-worker coming to me in tears asking me whether she should get a divorce and go back to a job she had out east, or stay with an intransigent husband and child and accept unemployment. I watched a co-worker selling off his furniture to help cover Cobra payments to carry them through the birth of their child. Out of roughly 100 scientists that I’ve worked with (i.e. in my “group” or department) since ‘97 only a little over a third are still in the Seattle area. I’ve spent almost three out of the last thirteen years in this area between paychecks. I know skilled scientists that hung it up to become tour guides, salesman, stay-at-home parents and retail clerks."

There was a Tiki torch along our Cargo Cult airport that burned for many years. It was labeled Zymogenetics. This one was a little different. Why did it burn so long?

The common thread, is that it will soon be gone. It goes on to live as a piece of a mega drug company. Of the hundreds of unemployed people, who will become tour guides, salesmen, stay-at-home parents and retail clerks? My hope is that these people find happiness. Those who find replacement biotech jobs must realize that they work in a cargo cult airport. We take someone from the watch tower, remove the 'coconuts with sticks for antennas' from their ears and we strap a wire around their body and tell them they are now a radio. It pays well for awhile but the duration of that paycheck is random. Zymo was long lived but what will happen next is more likely to be 'three layoffs, five mergers and and two company failings'.