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/