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"?

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?

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.

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!"

Priceless

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?

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.

Nonscience

"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.

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.

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.

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?

When Credentials Outweigh Capabilities

Credentials
–noun
1.
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.
2.
anything that provides the basis for confidence, belief, credit, etc.

Capabilities
-noun
1.
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?

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'.

What Did You Do To Cause This Recession?

An economist is an expert who will know tomorrow why the things he predicted yesterday didn't happen today.
Laurence J. Peter

A friend tried to get an advertised 10% off her phone bill. After 2 hours and numerous contacts she finally got a phone number to call tomorrow to see if that group knows how to get the discount.

When the economy went into the tank we ended up with a vast amount of Americans unemployed. Which ones could have helped customers get that 10% discount? Did any of those unemployed people have a job where they made the discount harder to obtain? Not everyone contributes to a better business. In any sizable group of people, some are good, some are bad. Which ones are the leaders and which ones are the smartest?

In our world we have valued individuals based on college education, job title, responsibilities and experience. Currently younger college educated people are having a hard time finding work as are the 50+ white collar workers. Like a piece of real estate, those two groups of workers have lost their value.

Was the cost of employing so many people not paying off? Or did the economy take away the business that paid the salaries. Anyone who has worked with a bad boss or a bullying HR department knows that not everyone is doing work that directly earns money. A software engineer may work 16 hour days developing a product only to one day find his job has ended. But business decision makers can be like cargo cult leaders and they may one day remove all of the useful people and leave behind an office full of white collar folk who have meetings all day wondering what to do next.

It is of course very complicated. Without sound business decisions, the money will dry up. The value of employing business decision makers is thus based on the companies financial health. The value of the product developers is based on whether or not people want to buy their product over the competitors. If you like X Box better than Play Station 3, you give your money to Microsoft. The business people must employ the product developers and direct them to make the best product. The business people must then shift the cost of business from R&D to sales.

But I end this post on a positive note. I have stepped out of the product development side of my own Cargo Cult business. For sanity purposes I am going back to my old ways of thinking more, working less. And I will write more.

A Drunkards Walk

'A Drunkards Walk' was a fine read. The reason it has resonated so much with the CCS is due to the randomness of the biotech business model. In our science, desired outcomes make everyone happy. When outcomes are not favorable, the laboratory technician who ran the experiment, the statistician, clinical trial doctor..., is grilled to determine what he/she did wrong. Does the desirability of results bias the judgment on experimental outcome?

In a Drunkards Walk the relationship between randomness and our interpretations of life are explored. On one hand, we have got some serious scientific problems when it comes to biology level scientists trying to distinguish between random and non-random events. But the scientists don't really put a company on the map. Investors do, and we need them to be ignorant of the lessons taught in "A Drunkards Walk".

Check out this comment from a biotech company yahoo finance message board: "@#$%^&* will either hit a home run or will be made to look like an idiot. Either way, I am still invested. Lottery ticket, hopefully a payout. I have lost before."

Thank you for investing sir.

At the End of the Day

I've been interested in the financial meltdown lately and how it is related to CCS. I recently watched a DVD with the Economic Hitman, John Perkins. As I've mentioned, I work in biotech for the money. The money is the sole reason for waking up and going to work each day. In better times perhaps I would try harder to find meaningful work. As it stands, I'm a son-of-bitch. John used to be the same way. Only he made a lot more money.

In the DVD, Mr. Perkins mentioned that the people who worked in the "Economic Hitman" field were not necessarily bad people. In fact, they may have been very honest people who believe they are working in the best interest of others. Yet Mr. Perkins, who worked in the same field, now feels the need to carry on a crusade to educate the world about the ways in which the rich are getting richer. He's different. He feels what was done was dishonest and those who work in high places should know better.

Cargo Cults are run by people who have always desired to be the boss. These people have always existed and they always will. Some are preachers in local churches. Some are CEOs and politicians. They love the power but feel most insecure when it is time for the planes to come. Religious leaders have it the easiest. The planes don't come in our lifetime. The afterlife is the promise. CEOs on the other hand have a problem. If shareholders start losing money then the CEO musts go. Politicians must pray the CEOs and religious leaders are pacifying the people during times of strife.

The scientist however thinks thoughts in a world aside from CCS leadership. He knows the ways to make the planes land, whether or not he/she has access to what is needed. CCS leaders have the power to keep themselves and their friends employed at the top for as long as they can stand it. Just look at the US Treasury and the Wall Street relationship. In spite of their failure, they have survived and they got even richer in the process. But John Perkins knows a thing or two about them and how they do it. John doesn't have the power unfortunately. He has his thoughts and he sees the damage before it is done. When the damage IS done, and a handful of people prosper as a result, he is not surprised.

So at the end of the day, when I head home from a day of Biotech non-science, I hang my head and hope for the day when I can work away from CCS. Is there a place in the world for people like John Perkins who leave lucrative positions and try to point out negative things to a tribe of people who only want to hear stories about the cargo. The world needs people who send out warnings that repeatedly come true. Not everyone wants to be rich. Some have a deeper purpose.

Are We Different?

Over the course of a few years I've come to a conclusion about biotech people. They are no more scientific nor any less religious than any other group of people. Most believe in the christian diety. Most have never heard of Richard Feynman. The story of N-Rays seems pointless.

Long ago people began to look at the world and wonder if they could discover things that no one had yet explained. By taking measurements for example, they soon learned that water boiled at the same temperature (more or less). When they were convinced that they had a fact they told others and challenged them to prove them wrong. A certain kind of person would find the study to be... interesting. Another kind of person would be confused as to why the would-be scientist had bothered to pursue their research.

In a group of 100 Americans, how many would be in the latter sub-group?

In the Cargo Cults, everything is known. The rituals are well established. The only thing to do is wait for the Gods to deliver the goods.

So in our biotechnology laboratory we can make proteins and cell lines and send them forth into the blood streams of animals to establish the simple fact, that our drug is the real deal. Our drug is going to be that airplane in the sky. We see it clearly.

In a group of 100 Americans, how many would see it clearly? Let's say that those 100 people work at the biotech company who made the drug. Do we all believe?

Did You Learn How to Believe?

I have a bad attitude regarding Biotechnology. I believe the financial interests spoil any chance of science taking place. In its place we build Cargo Cult Airports and occasionally make a whole lot of money from fools who believe our stories. The biggest fools however, are the ones who toil in the laboratories. They stand duty in that wooden hut with two wooden pieces on their head like antennas and they soon start to believe that they are indeed the controller of the airport. They wait for the airplanes in spite of what they have learned. They are now believers.

Yet I work in one of the Cargo Cult Airports. Why?

Money.

Life Coaches for the Life Sciences

Why do we have a life coach at our biotech company? Our "scientists" do need guidance in the ways of managing other human beings. That can be an important aspect of the service. But managers are hired to manage. Why not hire a "science coach"? The managers are also hired to do science.

The coach shows up in a 1992 Honda Accord. His 6'4" frame towers over the little car as he emerges desperately dialing someone, anyone, to make sure he looks busy on his way to our door. He could be here to visit our clinical trial leadership. He could be here to visit the HR person to recommend a new book for the in house leadership book club. Or perhaps the director of R&D... CEO? All people he has consulted with.

Does he have another job? Night shift at Target? Does he have an office? Does he know what DNA is or an antibody? No matter. He has his skills. We're dying to know what they are. But that is not information that is shared with most. It is another secret. Because we have secrets. The coach is one. What could he be teaching a science based company?

What to Say?

Lately I've been mulling over several topics.

Eli Lilly has a couple of cargo cult irons in the fire. Yesterday http://www.biospace.com/news_story.aspx?NewsEntityId=167679

But we expect dishonesty from those who practice the cargo cult science. More interesting is their own angst over being burned by the same kind of silliness. http://online.wsj.com/article/SB20001424052748704247504574604503922019082.html

Warren Buffet is qouted, "You don't ask the barber if you need a haircut". Is big pharma starting to get this concept?

The economic meltdown is another topic. Think of the financial system as a CCS airport. The meltdown is merely the locals who have given up on the arrival of the planes and gone home. It's an abstract concept. Is monetary value real or imagined? Do we gamble on the imaginations of "geniuses" or do they really have a system?

Lastly, tonight, Shadow Elite. I've just purchased this book, and have yet to read it. However I am intrigued by the notion. Is it possible that we look at our own Cargo Cult Airport and eagerly await the scholarly words of the leaders, yet off in the distance, there are those who know that the planes aren't coming? If so, how do they succeed in this type of pursuit?

These Airplanes Are Fake!

Imagine the leaders of the Cargo Cult Airport leading a group of people around their airport. They bring the people close up to the airplanes but never close enough to actually touch one. They show them the workers but never allow a conversation. If they did they would see that the airplanes are merely wooden replicas and the workers have no clue what they are doing.

This is a biotech website. Those who chose to look will see the white lab coats.

But alas, not all who contribute to the biz are cargo cult scientists. For example, some are there to make the product that goes into the clinical trials. These people have experience and expensive equipment that make biological products. They cannot survive for the long term making wooden replicas. They make real biological products. It is up to the biotech company to use the products to create the dream that one day the airplanes will come.

Now we see someone who has a real concern about the quality of the airplanes/drugs. The airplane/drugs must have certain attributes that are not properly ascertained by looking from a distance.

Long story short, we (my biotech co.) are being discovered. A contract manufacturer is asking questions about how we produced and purified and packaged our drug, an antibody. Not just how, but why did we do what we did. Our answers we not sufficient. The CMO is now doing what it does with less and less help from the little biotech who is paying them to do their job.

The moral of this story is that not all biotech is Cargo Cult. Although it is embarrassing to be on the wrong side of right and wrong, I am pleased to see a contract manufacturing company asking the right questions and getting the wrong answers... and knowing that they are wrong. 

A River Runs Through It

I'm currently faced with a situation that would have pushed me over the edge in my younger days. We are working in "process development" in a small biotech company. We spent a few years getting by, purifying antibodies on a routine basis. All of our methods seemed to have come from a contract manufacturer who was hired years ago to produce a drug candidate for us. Our people knew nothing to begin with, and after watching the contract manufacturer do their work, they knew very little. What our people did was to find out what buffers were used. That is all they came away with. They did not know why the buffers were chosen but they knew that they worked.

What we have now is a clear "Cargo Cult Science". (CCS)

Our contract manufacturers succeed. They must or they will not continue as an entity. We on the other hand can carry on for years, because we do not have to produce anything other than charts and graphs that can be presented at meetings with affluential people. Contract manufacturers produce our drug and they must not only convince the world that the protein exists, but it is in the very vials that they send forth! And they do it very well. We don't know how.

But we, in this little company, take the proteins in the vials and we take them to the Cargo Cult Airport. We incorporate them into our rituals and invite our investors to sit with us and wait for the airplanes to arrive. So far nothing but a whole lot of money.

Pfizer Shuts Down Several Airports

As part of its integration of Wyeth, Pfizer said it will close a total of six research facilities and ultimately reduce the work occurring at 20 research facilities into five main research campuses and nine specialized units around the world.

What were they doing wrong? Here they are admitting that the planes were not landing. They've restructured. Will the planes land?

It all seems so random. To the investor or the executive they have a new path. But what was really wrong? Why couldn't the millions of dollars, pHDs up the arse, cutting edge technology and the latest advances in medical science produce promising candidates?

Something was missing...

Science, Sequences and God

I used the Henderson–Hasselbalch equation to calculate the amounts of acetic acid and sodium acetate needed for a certain buffer. When the pH of the solution was taken it was exactly what it should have been.  This is the kind of science that the CCS likes.  Now consider the human genome project.  

After a fortune was spent on the project, and more than a few "leaders" of the sequencing became famous, what do we really have? Has anyone ever truly used it logically? It's a bunch of As Ts Gs and Cs.  I originally thought there would be patterns that a computer could pull out that would help us to understand what a gene is.  Unfortunately, most people believe they already know what a gene is.  The genome project has only resulted in the kind of science the CCS dislikes.  You take a finite set and you select a piece of the set that best describes your pre-conceived notion.  In the case of the genome project, they selected five people and they began sequencing their DNA.  When they were done they said, "wallah, the human genome, now go and cure diseases.  But don't ask us how to use this tool."  The "how" is science.  The sequence is a whole bunch of sequencing machines working day and night.  

Another such science is RNAi where you select a set of sequences to knock out a gene.  You select the best one.  You can't lose.

In the Henderson–Hasselbalch example, you can lose.  You can screw up the math and get the wrong pH.  Biotech companies practice the genome project and RNAi type of science.  A company selects a drug or some service and hires "scientists" to prove that it works.  The leadership are university trained scientists who find work in laboratories to be unpleasant and better suited for the lesser intelligent university trained scientists.  

This brings me to the point of this post.  One of the scientists who gained some fame from the genome project has been promoted to NIH director.  

http://www.bloomberg.com/apps/news?pid=20601087&sid=atJa8QDGj8QU

Here is the craziest part of it.

http://biologos.org/

Randomly Fumbling Through the Day

Quite often in our business we move from one experiment to the next, never analyzing the previous set of data.  After a while people begin to believe that such a logical process is not possible in our special set of circumstances.  

Take for example the case of the gender assay from AcuGen Biolabs Inc.  They claim a 99.9% accuracy in guessing the sex of your baby as soon as 5 weeks after conception.  Due to patent issues, they claim, they are unable to share with anyone the data from where this accuracy was calculated.  Statistically, how many tests would have to be done to verify that they can significantly predict male, female or twins with a 99.9% accuracy?  Can't we test this biotech company to make sure they are not selling a bogus product.  

But kudos for their method of sidestepping the FDA.  Each day we in biotech attempt to create data that we think will satisfy the FDA.  They do not tell anyone ahead of time what to do so we fumble along looking for things we think will help our case.  The real skill then becomes how to avoid exposing bad data.  Randomness allows less than favorable data to be hidden.  Well thought our research leaves you wide open for failure.  And that is a bad business model.

Stats

My career in biotech has been maddening.  But it is not biotechnology that is the issue.  The issue is statistical analysis of data.  This became very clear last week when some of us sat through a course in a software product that analyzes data.  A lot of time was spent debating what a sample was versus what a population was.  We even had people arguing over the term bogus results versus "not validated".  The useful aspect of statistics was not of interest to our group.  

There was a simple illustration about a lady who could tell the difference between tea with milk added versus milk with tea added.  The design of the experiment to test this lady was rigorous.  The people testing the lady were highly skeptical about her claim.  The design of experiment however, left out the possibility of bias on either side of the question.  In the end they all agreed, the lady could tell the order in which her tea and milk were combined.

When Feynman said, "So we really ought to look into theories that don't work, and science that isn't science." he seemed to touching on the powers of statistics to analyze experimental design.  Psychics and people who speak to the dead are best exposed using statistics.  Biotechnology can also be analyzed this way.  The real trick for our future is to find ways to get Biotech and the pharmaceutical industry to allow outside groups to analyze their data and their analysis of their data.  The thought of a group of MDs locking themselves in a conference room to make a recommendation to the FDA regarding research seems absurd to me.  The Design of Experiments is the whole issue behind the Cargo Cult Scientist.  

Can't Blog Very Well

http://www.youtube.com/watch?v=0XgmrMZ0h54&playnext_from=PL&feature=PlayList&p=BA10ADCB66375592&index=3&playnext=4&playnext_from=PL

Large Groups of Humans

Deliver Us From Evil, http://www.deliverusfromevilthemovie.com/index_flash.php, is a disturbing documentary that depicts an organization that cannot fail. The Catholic church was organized to promote the christian religion and to perhaps improve the morals of society. What it has become is a highly immoral group of men who do horrible things and protect each other from prosecution. They continue to sell their product, christianity and morality, but they've been outed. For those who choose to open their eyes to reality, the Catholic church is truly a criminal organization.



Something happens to large organizations after they reach a certain level. Banks aren't allowed to fail. Corporations are protected. Think of them as groups of people who got together and started making rules, setting up legal protections and hiring people to advance the cause. Eventually, they reach a certain level. Success. They can't fail. At this point a certain type of person begins to emerge as management material. That person understands that the group must not fail. When enough of these types surround a corporation they begin to protect the organization from any harmful reality. If your church is employing pedophiles who are raping the children of the congregation, you must protect the church from the negative press. When your corporation is losing money, you get creative with the accounting.



Which, of course, brings me to the merger of Merck and Sherring Plough. Their products are meant to make our lives better through chemistry and biology. But they were already big. The problem was that they were not succeeding at making new drugs. They know all about the FDA and fill finish production lines. They are good at many things, but not at creative science. So they merge. They know how to merge. It involves paperwork and meetings. There will be plenty of paperwork and meetings surrounding the merger.

Where will the new improved drugs come from? When large companies fail to develop their pipeline they go to the smaller companies. They must then make decisions that involve millions of company dollars. Decision making becomes more and more beaurocratic. Distancing oneself from accountability while remaining close enough to claim a piece of possible success is an artform. Not a science. The new protectors of Merck/Sherring will have to be very careful yet find replacements for the billion dollar drugs that will be losing patent protection. What will they do? With 90 thousand employees they have plenty of humans working on their cause. What will they do?

Optimism For the Seattle Cargo Cult Airport

http://seattletimes.nwsource.com/html/businesstechnology/2008667376_biotech25.html

"I'm fairly optimistic that this year will see good things for the industry," said ZymoGenetics President Doug Williams.

"We have some great, great research institutions here," said Chris Rivera, the new president of the Washington Biotechnology and Biomedical Association.

Next year at this time I will try and revisit this article. The CCS is not optimistic. It's not about the money. It's about things like RNAi and PhDs trying to be businessmen. It's about the product. In other words, the airplanes. Are they coming in 2009?

Is It Over Yet?

MDRNA Cuts Executive Pay, Freezes Salaries as Cash Runs Out
Luke Timmerman 1/23/09
MDRNA is running out of cash, and is drastically cutting down payroll expenses, according to a source close to the situation. The Bothell, WA-based biotech company (NASDAQ: MRNA) has asked executives to work for no pay, and has frozen employee salaries at $1,250 for the final two weeks of January, according to the source.
Matt Haines, a spokesman for MDRNA, said the company hasn’t done any layoffs, although he declined to comment on specifics about any payroll cuts. “As a public company, we cannot get into details of any cost-cutting we are taking at MDRNA,” Haines said in a voice message.
The company, formerly known as Nastech Pharmaceutical, has been trying to reinvent itself over the past year from a company that specialized in nasal delivery of existing drugs into one that develops new medicines that work via RNA interference, or silencing problematic genes. The company changed its name in June to MDRNA, removed CEO Steven Quay from the top job, and replaced him with Michael French.
The new boss has a track record in RNAi, as a former senior vice president of corporate development at Sirna Therapeutics, a San Francisco RNAi drug developer that was sold to Merck for more than $1.1 billion in October 2006. Still, he joined MDRNA when its work was at the very early stages of development and would require significant capital investment to create something of more value. MDRNA said it has 4 issued patents on RNAi technology, and has 304 pending applications. None of its RNAi work has yet advanced into clinical trials, leaving it behind leaders in the sector like Cambridge, MA-based Alnylam Pharmaceuticals.
MDRNA’s effort has also been plagued by its rapidly dwindling cash reserves. The company slashed 23 jobs in August, mostly among people from the nasal delivery business, leaving it with 58 employees at the end of September. But the cuts may have been too little, too late. The company had just $10.9 million in cash and investments left at the end of September, down from more than $41 million when it started the year. At the end of September, MDRNA’s last formal financial update to investors, the company said it had just enough cash to last “into the first quarter of 2009.” Since then, the company has been notified that it is in jeopardy of having its ticker symbol de-listed from the NASDAQ. The company’s stock traded today as low as 25 cents, with a market valuation of just $8 million. It hasn’t announced any new round of investment.
MDRNA in its various forms has been in business since 1983, and never developed a successful marketed product to push it consistently into the black. The company has run up an accumulated deficit of more than $241 million from its beginning through the end of September 2008, according to its most recent quarterly report. When French was hired, his starting base compensation was set at $340,000, and he was given 1.26 million company stock options, according to a regulatory filing.

Is Vytorin a Failure?

http://www.time.com/time/health/article/0,8599,1703827,00.html



If one had read Gary Taubes' 'Good Calorie Bad Calorie' they would not have been surprised by the results from Vytorins ENHANCE study. To the Cargo Cult Scientist, statins represent the holy grail of our current state of medical research. Statins are the biggest money makers in the industry. And they don't save lives. Diet and exercise are the best answer but you can't sell them in a pill. One study after another proves that they are not the answer. But we must have an answer. And the FDA knows what that answer must be: http://www.google.com/hostednews/ap/article/ALeqM5h6pzZiObVnCNNNsI0McxoMN8WZVAD95J8NK80

Goodbye Seattle PI

While we expect the loss of Biotech companies we do not enjoy seeing honest people lose their livelihood. We do get pleasure when people like James Bianco and Steve Quay are acknowledged as Cargo Cult leaders. They love money and they love power. Science is a bunch of words to them. The words can be used to extract money from investors. That money is used to create companies that create powerful positions.

Another group of people who live by their words are the fine journalists at the Seattle PI. They make less than 100K per year. They put out a product everyday. When they make a mistake they have to retract what they said. They also serve as a watchdog against government and corporate America. Sadly they are going to be silenced.http://seattlepi.nwsource.com/business/395463_newspapersale10.html

In terms of the Cargo Cult world, the newspapers report on the airport. Not just the promises, but the reality of what is happening out there on the runways. They look up to the skies 24 hours a day. Each day they report, " no airplanes have been spotted". Seattle will have only one newspaper. A day will come when a major US city will have no local newspaper. That will be the day when local government becomes as free as a biotech company to report it's own news.

Fires Are Burning Out

http://seattletimes.nwsource.com/html/sundaybuzz/2008613921_sundaybuzz11.html
http://seattlepi.nwsource.com/business/394854_northstar06.html

Note the ending of the first article and how it leads into the second.

...an investment fund with major stock ownership, which in December wrote to Northstar board members: "It would seem that some of you remain content to pay yourselves salaries from cash that belongs to stockholders while contributing nothing of any positive value in return."

With Cell Therapeutics, which has few, if any, institutional shareholders left since it became a penny stock, it's unlikely there's anyone to write that kind of letter.

Zing!

Analysts predict that Biotech will lose a third of its publicly traded companies. One third! They're on to us.

Rosetta

I missed the demise of Rosetta out here in Seattle. Merck bought this company back in 2001 for 630 million dollars. http://seattlepi.nwsource.com/business/22771_rosetta12.shtml

Things were going well in 20004. http://community.seattletimes.nwsource.com/archive/?date=20040325&slug=rosetta25

Then they discontinued the project last October. http://seattletimes.nwsource.com/html/businesstechnology/2008300061_rosetta23.html

It's a classic Cargo Cult scenario. We have a technology that will change the way drugs are discovered. Where are the drugs? Who is talking about why Rosetta failed to do what it promised? Only the Cargo Cult Scientist is wondering why computer programmers couldn't turn human speculations (medical research) into the fountain of youth. Too much BS was piled too high. So long Rosetta. I know you'll get an office or two in New Jersey but you won't produce any drugs. Silly.

2009 Predictions

There are not many companies left in Seattle. There are more than the CCS is aware of but many of the big players went down or were at least knocked down a peg last year. 2007 was already covered at the beginning of 2008. Dismal. But what about the upcoming year? I know that people will have a bias that the CCS is optimistic about the upcoming year of scientific discovery among the scientists of Biotech. But wait, I've got to admit that I can be a little negative from time to time. For example:

Gilead is expanding and hiring: http://blog.seattlepi.nwsource.com/thelifesciencesblog/archives/141124.asp

I predict they will grow in the most foolish ways imaginable. They have the brass from the ruins of Corus and they have no idea what they are doing. They do have a lot of money to spend however and they will do so for the sole purpose of creating a Cargo Cult Airport. It will be a nice facility with lots of promises presented on all of the lastest equipment available from Dell and software from Microsoft.

But I can also be positive. For example:

Amgen will rebound. http://seattlepi.nwsource.com/xconomy/392982_xconomy7075.html
It's an untestable osteoporesis drug. No harm means no foul. Lots of money will be handed over and the leadership will go back to spending the profits on their own Cargo Cult airports within the organization. Their RNAi projects will quietly start to fade and antibody work will be pumped up using new technologies bought from smaller companies.

I'm not an insider. I'll find out what is going on nonetheless. It makes life in the biz much more interesting.

How Can You Lose?

"Harry is an experienced portfolio manager who has a proven track record of success."

So says Adam Banker, a spokesman for Fidelity Investments. Harry Lange runs Fidelity Investments' Magellan Fund. The Magellan Fund has seen assets decline 83 percent since reaching a peak eight years ago. The 18.6 billion dollar fund declined 52 percent this year, trailing 99 percent of competing funds.

Somebody had to finish towards rock bottom. It makes you wonder what funds trailed the Magellan Fund. Did their managers also have a proven track record of success?

My interest in the financial worlds folly is directly tied to Cargo Cult philosophy. Clearly the world has seen behind the Wizard of Ozs' curtain. They didn't see failure coming anymore than they saw success in the past. These are the same people who invest in Biotech. Someone points out that RNAi is a hot investment because SIRNA sold for over a billion dollars. Fund managers get their clients checkbooks out and go looking for RNAi companies. Meanwhile it is no certainty that any of these people know what RNA is, let alone RNAi.

I'll end with a funny story about a biotech investor. This person was looking for investments in a hot biotech field he had just heard about. He called the investor relations department. A very nice lady who had just started in the department answered the phone. She had just been promoted up from her previous position as receptionist. Before that she spent 7 years as a secretary at the local high school. The investor spoke authoritatively to the nice lady. "Yes, can you tell me if you have any research taking place involving monoclonal antibiotics?"

Wallstreet Logic and Biotech

Why is it that Treasury Secretary Henry Paulson didn't originally ask for 1.5 billion dollars for his bailout plan? The original amount of 700 billion was a shock. The 800 billion seemed to be less appalling. Not only is it 100 billion dollars more, it comes right on the heals of the 700 billion. The most likely answer is that Paulson knew he needed a blank check but knew better than to ask for one. So he went about it this way. Creating an illusion of stability is the plan. Investors will buy into illusions.

This is clearly a Cargo Cult approach. We've noticed that during more prosperous times our bankers were flush with cash. Now they are all facing annihilation. If we slather them with cash then they will appear to be well again. But what about the fact that they ran out of that cash? Will they run out again?

Biotech financing works this way as well. We don't know how much we'll need. Give us millions and we'll get started. Give us more millions and we'll keep up the good work. And just keep on giving until we succeed. But we rarely succeed. Now we are watching our government give billions to individuals who also have a promise.

Another issue is whether or not the meltdown is really bad for us. Gas is now 1.85 per gallon. Real estate is dropping which is bad for the profits I would have needed to make a downpayment on the next place. But I now get to select from a whole new set of properties for my next place. I'll have less to put down but I won't need as much. It appears that our economy is merely correcting for a decade or more of inflation.

If 100 people live on an island with only enough food to comfortably feed 100 people then you have to figure out how to ration the daily intake. If you do it wrong then some will have too much and some will have too little. It takes a special kind of person to admit that they are getting more than their share. They must also decide who gets their extra food. What is needed is a governing body on this island that knows how to ration. Some will gather the food, some will prepare the food and some will search for new sources. All will need food. The important thing for the governing body is to not make any one group of the team so important that another is eliminated.

The main point today is that money fuels wallstreet and it fuels biotech. It's great when you have it but humiliating when it's gone. So somewhere along the way to failure we have to take a look at how effectively were using our limited resource, money. Once again... Dr. Richard Feynman:

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

And I might add, look into it sooner than later.

DOH!!!

http://health.msn.com/health-topics/colon-cancer/articlepage.aspx?cp-documentid=100220689

Chaulk up another swing-and-a-miss for medical science.

Back to RNAi

We recently put the flame of Nastech out. Tight junction technology didn't work!!! Nastech lit the side of our runway for many years. Then one day it ended. The name was changed, the CEO was replaced and the stock became a steal at 15 cents a share. The name of the company was changed to MDRNA, as in RNAi. The new CEO was in fact the old CEO of SIRNA, as in siRNA. The latest addition to the MDRNA staff is the old CSO of SIRNA. SIRNA was sold for 1.1 billion dollars to Merck. Can lightening strike twice?

The first question is, what has Merck done with their aquisition of SIRNA? Any regrets? 1.1 billion is a lot of money. One might hope to make that kind of money from an approved product. Merck did not buy an approved product. The second question is, what does MDRNAs new brain trust plan to do with the 12 million bucks left behind by Nastech? The SIRNA patents are in the hands of Merck leaving only the brain power behind SIRNA and the power of RNAi.

The brains behind this new flame along our runway have a major obstacle. Can they stay in business long enough to get a drug approved? The villagers must be very enthusiastic, but will they hand over their money? If not this latest RNAi project will not get off the ground. If they get funds they will be free to conduct the science. We are watching.

A Villager Speaks Up

One of the most outspoken villager, who looks up daily to spot the cargo planes, has detected a way to spot a false profit: http://www.thestreet.com/story/10443120/1/dont-get-burned-by-the-next-cell-genesys.html?puc=googlefi&cm_ven=GOOGLEFI&cm_cat=FREE&cm_ite=NA

Mr Feuerstein makes a living telling the other villagers, who look to the sky, what it is they should expect to see any day now. But he speaks from the investment perspective. The science is something he peppers into his columns. He doesn't know. It would be interesting to see an accounting of his ability to predict good from bad investments. Are his predictions best measured by his understanding of the science? Would a random stock pick make more or less?

Keep looking up Mr. Feuerstein.

Once again, Feynman; "So they've arranged to imitate things like runways, to put fires along the sides of the runways, to make awooden hut for a man to sit in, with two wooden pieces on his headlike headphones and bars of bamboo sticking out like antennas--he's the controller--and they wait for the airplanes to land."

I will promote Feuerstain to control tower supervisor.

A Cancer in the Health Care System

What if there were doctors for the health care industry. A company like Pfizer goes to the doctors office compaining of a weakness in sales and a bleak outlook for the future of their research efforts. The doctor says, "take off your marketing department please."

Pfizer: Things like this keep happening to us:

http://ap.google.com/article/ALeqM5g--AosBLRVpNsiYYtzTePEXOUzoQD93S9NGG0

Doctor: Hmm. I see you have an honesty problem.

http://www.nytimes.com/2008/10/08/health/research/08drug.html

Pfizer: Well, we have to make money.


We continue to be shocked at the lack of outrage against these common practices. Which executives made the decisions that led to the conclusions in the second article? What about repeating such dishonesty over and over and occasionally getting caught? The industry has a disease. It is incapable of being honest when negative data presents itself. What is the cure?

Cargo Cult Scientist Gets Snubbed

The Nobel Prize committee for medicine has failed to honor Dr. Robert Gallo for his contributions to the HIV/AIDS hypothesis. While it's true that he appropriated the HIV virus from Luc Montagnier, he did convince the masses that this was the cause of HIV. A true Cargo Cult Scientist does not succeed by solving tough questions. He succeeds by convincing people that he knows how to make the airplanes come from the sky. The better the Cargo Cult Scientist the longer he can keep the masses looking up and waiting. The message from Stockholm today seems to say that it was not Dr. Gallo who started us all looking up.

Now would be a good time for the national media to explain why Dr. Gallo was snubbed. He was snubbed because he is a dishonest person. Many people know this yet he continues to work in science. Dr. Prusiner, the 1997 winner of the prize put it this way: http://aidscience.org/science/298(5599)1726b.html.

There are many prizes for the many promises.

Have a Plan

Lately I've been thinking about the way in which ideas become accepted. The Cargo Cult natives saw the cargo emerging from the big metal birds and a desired outcome was born. Now all they needed was a plan. They watched the Allied forces carefully and began piecing together their plan. The desired outcome however was the most important piece of the plan. The ideas of how to acheive the outcome took a back seat while the leaders dreamed of the cargo.

We recently experienced the Republican and Democratic national conventions. The mission was to convince the majority of America that one party will provide a better future than the other. The melt down of wall street however is an excellent example of our political and corporate leaders ability to predict and shape the future. Our government is going to put up 700 billion dollars (this week!) to "fix" the problem.

But what about 2 weeks ago? Was anyone preparing for the bailout? What was being done 2 months ago? When did this government bailout start to take shape? We now have our desired outcome. We want the economy to be strong. That is our cargo. What is our plan? Bail out the banks so they can go back to making loans.

How did the ideas that went into the bail out plan gain acceptance?

The 700 billion dollar bailout does not guarentee success. It is a plan however. For the politicians, a plan is all that is needed. Even if the plans spells the end to the great American era. It doesn't occur to the Cargo Cults that there plan is not working. Simply carrying out any plan gives off the impression that work is being done.

Only a proper scientific method will bring about a proper change. Compare the actual outcome to the desired outcome. The ideas that were accepted may have lead you astray.

The Psychology of RNAi

This summers reading brought me in contact with a most beautiful book on the subject of randomness. The book is called "The Black Swan". In it you will find heretical discussions such as, "Academic success is partly (but significantly) a lottery. It's easy to test the effect of reputation. One way would be to find papers that were written by famous scientists, had their authors identities changed by mistake and got rejected. You could verify how many of these rejections were subsequently overturned after the true identities of the authors were established."

The painful truth about science is that it is run on the most non-scientific means of judging a persons work. Reputations rule. Good solid science will do you no good if you cannot convince the powers that be that they have missed something. This is not an easy task due to the arrogance of power. If you dare challenge someone like a David Baltimore or Craig Mello you had better have a powerful group of cohorts willing to back you in your battle.

The CCS knows this and is under no delusions that he is actually battling the powers that be. This is rather an exercise in psychology. What does any person have to do to affectively be heard? Write a blog? Ha! Have a great idea? Ha again. Great ideas can have just as hard of a time being sold as bad ones. In fact, the scientific merits of an idea is not as important as its presentation. Who is presenting the idea. Are they confident? Is the idea presented in peer reviewed journals, scientific meetings or books? Does the idea fly in the face of current thinking?

Billions of dollars have been spent and many more are on their way out the door for RNAi to be used as a drug. Beyond that, RNAi has been the bane of many a research associate whose job it is to use RNAi to knock out genes. It's like using a feather to hammer nails. But no one is going to listen to a guy who wears a white lab coat daily. No one is going to publish a paper stating that RNAi has yet again failed to produce knockout data. The idea that it doesn't work is no longer being accepted. Like gene therapy however, it will cease to impress and thus be put on the back burner. One day the real story behind what happened in the early studies of RNAi will be known. Until then we must accept that we are in the middle of a common situation in the history of human reasoning. We are convinced that we know the truth. We no longer require evidence to the contrary. Yet the planes are not landing.

http://www-tech.mit.edu/V125/N50/50van_parijs.html

This is an old story. This marks a new chapter in the CCS. We will now make it our mission to explain why this (RNAi) happened and how it will end. We have learned much from gene therapy and the demise of hundreds of biotech companies. Tens of billions of dollars are gone but there is something to be learned.

Just for fun, we start with a Harvard PhD who is fired from MIT after a rather successful beginning to his career. As you read about this story please think about the environment that make it possible. Harvard? MIT!!! But... but... PhDs? 461 citations. But there was a Nobel prize awarded for the RNAi story. Why would anyone in such a world have to cheat?

One Flame Out, One Flame Close Behind

http://seattlepi.nwsource.com/business/366495_nastech11.html
http://blog.seattlepi.nwsource.com/thelifesciencesblog/archives/141684.asp

Nastech is no more. Therapeutics will be done soon as well. Notice the name change at Nastech however. Cell Therapeutics may do the same thing. There is much to learn from companies like these who promise the cures. They take until they can no longer get away with it. Then they change their names and go back for more.

Sirna Sold For 1.1 Billion!!!

As I mentioned in the last post, a company called PhaseRx boasted that they are an RNAi company. What's the big deal about that you ask? SIRNA SOLD FOR 1.1 BILLION DOLLARS! So let's give PhaseRx some money!

Do you think that is a silly thing to say? How can a bunch of grown men with PHDs and MDs get together and hoodwink investors so easily? Does PhaseRx not have to present the scientific merits of their RNAi company?

In more recent news, the notorious Dr. Quay of Nastech Pharmaceuticals discussed the ruins of his biotech company today. In an attempt to ease the suffering of his investors he spoke glowingly about his spin-off 'MDRNA' a new RNAi company. There wasn't much information about the last five years of RNAi research under the old banner of Nastech. But he did mention this interesting fact:

SIRNA SOLD FOR 1.1 BILLION DOLLARS!

Who will be the first to go? MDRNA or PhaseRx? Will Merck keep spending money on SIRNA projects? The CCS will be on the lookout. Our eyes cast to the skies, we look for the kind of cargo that only billions of dollars can summon.

Would You Work for This Company???

Seattle Biotech has a new management team that has been sued by their investors. http://seattletimes.nwsource.com/html/businesstechnology/2004127544_cellcyte16.html

Okay, so that is old news. We also have a new fire to light our runway. And they specialize in RNAi!!! They have the old Nastech CSO who was "resigned" recently after years of not making RNAi work there.
http://seattletimes.nwsource.com/html/businesstechnology/2004247523_biovc28.html

Welcome to the airport.

What's in the News

'In the South Seas there is a cargo cult of people. During the war they saw airplanes with lots of good materials, and they want the same thing to happen now. So they've arranged to make things like runways, to put fires along the sides of the runways..."


We here at the CCS look at each biotech hub as a cargo cult airport. Seatte, the bay area, San Diego, Boston, North Carolina are all airports. The fires along the runways are small biotech companies.

The seattle cargo cults had a bad week.

Cell Therapeutics throws a 30K$ party after laying off 31 employees to save money.
http://seattlepi.nwsource.com/business/351048_cti13.html?source=rss
Amgen lays off 130 employees... up from the 50 they anticipated. They found more useless people than they originally thought they had hired?
http://seattlepi.nwsource.com/business/351138_amgen14.html
Dendreon can't get a break!
http://seattlepi.nwsource.com/business/351210_dendreon14.html
Nastech is one step closer to the end.
http://seattlepi.nwsource.com/business/350985_nastech13.html
Zymogenetics has layoffs after finally getting a drug approved.
http://seattlepi.nwsource.com/business/351223_zymogenetics14.html
CellCyte is a ridiculous company!!!
http://seattlepi.nwsource.com/business/351230_cellcyte15.html
The CellCyte CEO did lied?
http://www.sequence-inc.com/fraudfiles/2008/01/13/usana-executives-arent-the-only-ones-lying-about-their-credentials/

Sheesh!!!

A Burning Flame Going Dim

We think of biotech companies as bright burning flames that illuminate the runway of our Cargo Cult airport. We think of technologies such as RNAi as the fuel for the flames. Today we are concerned about our Nastech flame.

On January 16, 2008, Novo Nordisk A/S ("Novo") advised Nastech Pharmaceutical Company Inc. that Novo intends to cease development under the feasibility study agreement that the parties entered into in March 2006.

Jan 22 (Reuters) - Nastech Pharmaceutical Company Inc (NSTK.O: Quote, Profile, Research) said it may periodically sell up to $50 million in debt securities, common and preferred stock, warrants and units.

The company said it intends to use the proceeds in part to fund its clinical research and development programs.

Is the end coming soon? How will it end? Will they rebound??? We are watching.

A New Set of Questions for Scientists

Merck and Schering Plough make a drug called Vytorin which combines Zocor, a cholesterol lowering statin, with Zetia, a drug that limits cholesterol's absorption into the body. The ran a trial that was hoped to show that this drug was more effective than Zocor alone in slowing the growth of arterial plaque, which can lead to heart attacks. It wasn't. Vytorin users did see a larger drop ini cholesterol than Zocor users. The decline however didn't result in a improved arterial health. http://www.revolutionhealth.com/news/?id=hd-611715&s_kwcid=vytorin934891494

Shocking news to the scientists and doctors working for the drug companies. They just had no clue this would happen.

Folkmans Delivery Problems

Dr. Judah Folkman was a rising star with several publications and patents on anti-angiogenisis factors. The problem was that no one was able to reproduce his results. From his book "Dr. Folkmans War":

Soon after he began shipping endostatin to researchers around the country, Folkman heard that the drug had become inactive by the time it got to some of the laboratories... The recipients reported that the drugs were having little or no effect on cancer-bearing animals. Folkman was alarmed, needless to say. Any such report carries with it the suggestion that somehow the original research was wrong, or worse, that the results had been embellished.

Folkman and his colleagues soon noticed that the problem seemed to be only with batches that were shipped to distant places. The endostatin being tested in local labs was fine. So the problem, in all likelihood, was in the shipping.Like many drugs or biomedical compounds, the endostatin was being frozen in small plastic vials, packed in dry ice, and was sent out via Fed Ex. Folkman began doing experiments to figure out what might be going wrong. First, they found that the problem was not caused by freezing. When they froze a vial of endostatin, then thawed it, the drug worked normally. So how could transportation hurt it? Hoping to find clues they packed a sample in dry ice, stowed it in the trunk of a car, and drove around Boston with it. Sure enough, when they brought it back into the lab and thawed it, the endostatin didn't work. But why?"

The answer they later came up with was that the dry ice that the drug was packed in bathed the solution in carbon dioxide that had seeped through the vials. The result was the lowering of the pH that inactivated the drug. The solution to the problem was to put the drug into glass vials for shipping. The results of this experiment were not covered in the book.

Judah Folkman Is Dead

No sacred cows here. Dr. Juday Folkman died of a heart attack this past week at the airport in Denver. He had a great career in medicine. He was an MD surgeon who had a second career as a PI in a laboratory that explored the involvement of blood vessel in tumor growth.

The CCS does respect Dr. Folkman for offering up a new idea to the establishment and proving that tumors need blood. But then all cells need blood for oxygen and to carry away their waste. This should have been less heresy than it was. The real issue we have with Dr. Folkman however is his role in bringing corporate america into academia.

Dr. Folkman had spent a long time looking for a tumor angiogenesis factor that he decided had to be secreted by the tumor. What he needed was money to grow up large amounts of tumor cells to increase the odds of finding the factor. Monsanto was eager to give him what he wanted. The grant he was given and the terms of the deal swung the academic doors wide open for the corporate world. Their money could now buy access to the usefulness of our university system.

What they wanted of course were patents. They wanted to lay claim to the good work being done, not in their laboratories, but in the superior labs of university scientists. In my next post I will recount a humorous ending to one of Dr. Folkmans corporate sponsored R&D projects. For now I will end with the moral of this story:

The introduction of corporate minds and money into the world of science has been a disaster. In many ways, it began with Dr. Folkmans desire to become a scientist.

Is It Dishonest?

Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK) announced today that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. patent application No. 10/976,942, entitled "Phage Displayed Trp Cage Ligands." The patent application has claims that relate to a novel, high-throughput method for identifying peptides which can bind to specific cell types.

"A major obstacle in the development of safe and effective medicines today is the inability to target the therapeutic directly to the cells of interest," stated Steven C. Quay, M.D., Ph.D., Chairman and CEO of Nastech. "The technology of this allowed patent provides Nastech with a process for rapidly identifying peptides that target specific cells. These targeting peptides can then be combined with therapeutics to enhance overall delivery and overcome this key challenge in drug development."

Why then did Nastech sack the Phage Display group in 2006. The Cargo Cult Scientist knew members of this team and the reason they were given was contrary to the above quote from the CEO. It just wasn't working. The question then is simple. Is this dishonest?

In Cargo Cult terms, yes this is dishonest. They stood at the airport and employed their technology. They looked to the sky and no planes came. They sent the staff home. A couple of years later they still talk about the technology. Their government has given them a nod of approval but no planes have come.

FDA Science

Does Dendreons cancer drug Provenge really work? After hundreds of millions of dollars spent on research and careful analysis from the MDs and PhDs of the medical science community, it's now up to the United States Congress to analyze the analyzers.

"two members of the FDA's advisory committee who opposed the drug's approval -- Howard Scher of the Memorial Sloan-Kettering Cancer Center and Maha Hussain of the University of Michigan -- had conflicts of interest.
"There is reason to believe that serious ethics rules were violated by two FDA advisory panel members in their decision, and that these violations played a role in the subsequent FDA decision to not approve Provenge at this time," said the letter, signed by Reps. Mike Michaud, D-Maine; Dan Burton, R-Ind.; and Tim Ryan, D-Ohio.
The congressmen said Scher was a lead investigator for a competing cancer drug..."

http://seattlepi.nwsource.com/business/343479_dendreon14.html

CTI Kicks Off a New Cargo Cult Season

Viewpoint #1

SEATTLE, Nov 21, 2007 /PRNewswire-FirstCall via COMTEX/ -- Systems Medicine, LLC (SM), a wholly-owned subsidiary of Cell Therapeutics, Inc. (CTI) , announced that cumulative preliminary results of a phase I trial combining cisplatin with brostallicin in patients with solid tumors that had relapsed or were resistant to front-line treatment were presented at the Highlights in Oncology meeting in Naples, Italy, on Tuesday, November 20, 2007. Cristina Geroni, Ph.D. of Nerviano Medical Sciences (NMS), which developed brostallicin, summarized the basis for the phase I trial design. The trial is based on data demonstrating tumors with high levels of GSH/GST, common in platinum-resistant disease, are more susceptible to the killing effects of brostallicin. High levels of GSH and GST are associated with resistance to most standard chemotherapy drugs
"Our phase I and II experience with brostallicin in over 160 patients demonstrates encouraging anti-tumor activity in a variety of solid tumors, with more than 50% of the patients experiencing at least disease stabilization," said Steven Weitman, M.D., of Systems Medicine.
The preliminary results from the first 21 patients treated in the phase I combination trial with cisplatin showed similar results, with 14 of the patients experiencing stable disease and half (50%) of those 14 patients having durable stable disease for more than six cycles of therapy. Toxicities were mainly hematological and were manageable and reversible in this heavily pretreated patient population

Viewpoint #2

Cell Therapeutics stock falls on treatment study results

Seattle's Cell Therapeutics Inc. reported the results of an early-stage study of a cancer treatment, which combines two drugs, brostallicin and cisplatin, Wednesday. Of the 21 patients with tumors treated in the study, 14 did not show any changes -- positive or negative -- in the progression of their cancer. Cell Therapeutics said side effects were manageable and the company expected to advance its studies. The company's stock fell about 17 cents, or about 6 percent, to close at $2.38 on the Nasdaq stock market.

I believe it was John Allen Paulos who pointed out the medical science can be easily corrupted by psuedoscience. Sick people can either get better, stay the same or get worse. The first 2 situations can be attributed to your drug. Once you apply statistics you have protected yourself with "science". Two thirds of the patients in the Cell Therapeutics study stayed the same. They did not get better. Is this positive news?

More on CTI

http://seattletimes.nwsource.com/html/businesstechnology/2003670653_cell18.html

The Year Gone By

I'll let the Seattle Times lay it all out for you. They are so much nicer than me.

http://archives.seattletimes.nwsource.com/cgi-bin/texis.cgi/web/vortex/display?slug=biotech12&date=20071112&query=biotech

I've been silent for so long waiting for one big write-up and here the Seattle Times has done it for me. But I will make a few comments regarding the future of Seattle Biotech. The Accelerator companies will soon be facing tougher customers now that they have obtained multi-million dollar payoffs. Of course their investors assume they are just taking off. Cargo Culters know that the main goal is to get paid. The secondary goal is to get out before the S hits the fan. 2008 will be a critical time for VLST and Spaltudaq. Homestead may have already disappeared without any official notice. No thoughts on the others.

So I raise a glass and toast the Cargo Cult Airport otherwise known as Seattle Biotechnology. Many a flight was cancelled or delayed this year. But we'll keep looking up. The Cargo Cult Scientist is always on the lookout.

Video - CNBC.com

Video - CNBC.com

Nastech

RNAi has finally been mentioned in a Nastech press release. They are spinning of the RNAi research into a subsidiary company called MDRNA. And the stock went up on this news!

While Nastech themselves had 5 years to create an RNAi drug, they are now claiming that the new company, MDRNA, will be seeking funding in the near future. Nastech screwed up the rest of their company so badly that they must now cut out RNAi research in order to survive. In the process they intend to send out their business people to ask for more money.

We here at the CCS would like to meet the people who intend to invest in MDRNA. We got a nice bridge we'd like to sell them.