Teaching the Dog and Pony Show

From the website of the Biotechnology Institute:

Biotechnology has a wide variety of career opportunities ranging from sales and marketing, to research and development, to manufacturing and quality control and assurance.

Are these really the primary high paying jobs in biotechnology? This is where science goes awry. The Cargo Cult leadership needs people in these positions and they need to start training them how to think as soon a possible.

In the cargo cult science speech, Feynman spoke of a man who ran the Institute of Parapsychology.

This man also speaks about a new institution, in a talk in which
he was resigning as Director of the Institute of Parapsychology.
And, in telling people what to do next, he says that one of the
things they have to do is be sure they only train students who have
shown their ability to get PSI results to an acceptable extent--
not to waste their time on those ambitious and interested students
who get only chance results. It is very dangerous to have such a
policy in teaching--to teach students only how to get certain
results, rather than how to do an experiment with scientific
integrity.

You can teach quantitative analysis, organic chemistry, physics and biology but you can't teach biotechnology. At least not in the manner described by the institute of biotech. You can teach the history of biotechnology. You could try and find a coherent pattern in the organization of tasks that start from idea and end with a product that is sold for money. You could spend years trying to explain how the financing of the business used to work and what the future challenges are. You cannot teach biotechnology as if it were a learnable subject, being taught by those who have already learned how it works. The field is far too complex.

James Randi spoke of a young girl who developed a test for psychic energy readers. She made a barrier between her and the reader. There were two holes where the psychic put his/her hands through. The little girl would then place one of her hands under the right or left hand of the psychic. The psychic had to select which hand based on its readable "energy". Twenty readings were done to rule out random guessing.

Did this little girl have to learn about psychic ability? Did she have to study at the Institute of Parapsychology to conduct research in the area of psychic energy? No, she was conducting a study on whether or not a random pattern could be discovered in what appears to be non-random event. A randomness test could have also been done by tossing a coin in the air. She also did not have to attend a course on how the U.S. Mint makes coins! The real science was in identifying a random set of information that appears to be otherwise and to use statistics to highlight the randomness. The dog and pony show was in identifying a random set of information that will catch the judges eye.

Our mission is to engage, excite, and educate as many people as possible, particularly young people, about biotechnology and its immense potential to heal the sick, feed the hungry, restore the environment, and fuel the economy.

The mission is admirable but we are getting close to teaching kids what to think, not how to think. Biotechnology has been a failure. The adults have not yet figured out how to accomplish the goals listed yet they purport to teach the next generation. We are not "there" yet. There is no "there" there. Let the kids do science projects and let them meet the president. But before we start an institute for biotechnology, let us step back and figure out what biotechnology is. We have to separate the science from the dog and pony shows. The dog and pony show is what they are teaching at the institute.

Lessons From a More Advanced Field

Long ago I worked as a photographer. I learned all about setting the F-stop so as to not over or under expose the film. I learned how to process black and white, color, and slide film. I printed photographs in black and white and color. I shot portraits, crime scenes, ceremonies, and just about anything that required a professional quality image. For five years I honed my skills. I left it all behind one day and went to college to study biochemistry. Most of the skills that I learned are no longer required. Exposures on digital cameras are well balanced. Digital pictures can be corrected for using computer software. Prints come out color balanced. The exposure and contrast is taken care of via the software as well. Everything that I did subjectively is now done by objective physical qualities in the camera and by image software.

In a period of roughly 20 years the field of photography changed dramatically. It's easier now but a new set of skills are required. What brought about the change was science and engineering. What about the laboratory skills I now have in the field of biotechnology?

The science that I speak of is not medical science. In order to bring about the proper changes needed for biotechnology a new science must be elucidated. If you put a small strand of RNA into a living organism what happens to the RNA? Never mind what happens to the living organism. Focusing on the outcome of the cell culture, mouse, or the human being is ignoring the interaction of the drug and its host. The human body is also dealing with the disease. What is the fate of a foreign molecule that we design and introduce to a living organism? What happens when we change the living organism? If I have the same CDR regions in a Fab, Fab2, and a full length antibody, what is the fate of the three molecules that are the same only in the CDR region? The CDR region is what interacts with the drug target. The rest has to deal with the living organism. Perhaps they will all block the target in the cell culture but only the full length antibody will find the target inside the human body.

Here is a real time example of the kinds of questions that are too often not asked. Roche this week announced a new antibody;

an antibody with two arms. One arm was the anti-BACE1 drug; the other docked with a receptor called transferrin that carries iron to brain cells, providing a ferry across the barrier.

The system allowed the researchers to deliver anti-BACE1 to the brains of mice, blunting the impact of the BACE1 enzyme and cutting in half the amount of amyloid in the brains of mice 48 hours after injection

I am assuming that the molecule has one CDR region that binds to the transferrin receptor, and the other binds to BACE-1. How does the antibody dissociate from the receptor on the other side of the blood-brain barrier? What percentage of the drug load goes through the barrier? How does the drug reach the barrier in the first place?

Other issues are of course the amyloid beta story. The amyloid beta protein could run into a rotten bunch of brain cells that are kicking out amyloid beta denaturing agents (low pH, enzymes...) that will make the long journey of the anti-BACE molecule futile. Rather than relying on the endpoint that Roche and friends have set forth, someone should look at the entire picture from a scientific standpoint. Roche and friends wanted to tell the story that they've told. What does science have to say about it? What do we know about the measurements they took? The story they have told is more of a narrative rather than a factual description of their molecules journey into the brain and into the cascade of events involving amyloid beta. The solution here is an electronic notebook that researchers at higher levels must keep. The narrative approach to science of higher ranking scientists is an issue that software engineers can overcome. But don't ask the Bioscience PhDs to help design the software. They are not good at that type of thinking and they stand to lose a lot of BS room that they need to continue their careers. But it is their careers that have been a hindrance on advancing the field.

Photography was not advanced by photographers. Scientists and engineers were asked to answer a specific set of questions that lead to an improved system. Likewise, biotechnology research will not be advanced by anyone with a PhD in Microbiology, Immunology or Pharmacology. The sciences that rely heavily on math must get involved. Design of experiment is an example of statistics being used to help Bioscience people understand what has been missing in their research. For 30 years the big words of medicine have been used to bring in the big bucks. Now is the time for the big concepts of science to be used instead.

A Biotech Incubators Success Record

Accelerator puts up 1 to 2 million dollars, lab space and some admin support to start promising new biotech companies in the Seattle "build it and they will come" Lake Union area. They have been around since 2003 so it is interesting to see how things have gone since then. They've started up twelve companies.

1. VieVax 2004
2. VLST 2004
3. Theraclone 2004
4. Homestead 2005
5. Allozyne 2005
6. Seridigm 2006
7. Recodagen 2008
8. GPC-RX 2008
9. Mirina 2008
10. Xori 2009
11. Acylin 2010
12. Oncofactor 2011

So what happened? If you click on the link above you will see early success in series B financing and a long dry spell since then. Did financing dry up in late 2007 or did Accelerator start making bad decisions around this time?

The latest company to come out of Accelerator may be an indication of what is happening inside the offices. The company will be ran by Sarah Warren a 29 year old, newly minted PhD immunologist. Warren will develop experimental antibody drugs against biological targets selected by Carl Weisman, the Accelerator CEO. Weissman came up with his idea about 18 months ago.

“If you can stop cancer from blunting the immune system, then you can free up the immune system’s ability to clear the cancer cells,” says Weissman.

Accelerator seems to have left their old business model behind.

The evaluation of potential Accelerator companies is very rigorous and the process is extremely selective... Accelerator has seen and reviewed more than 500+ proposals, executive summaries, and business plans.

Why then are they now starting a company based on Weismans simplistic, select target/make antibody, idea? Why have they chosen a 29 year old with no experience in the real world? Is she really going to run the company?

Ms. Warren will report to the Accelerator scientific advisory board that includes Pat Gray, (Accelerator’s chief scientific director), David McElligott (lead scientist at Mirina, Accelerator) Ken Grabstein, (chief scientific officer of Allozyne, Accelerator) Mike Deeley, a former senior director at Icos, Steve Gillis, a managing director at Arch Venture Partners; Larry Tjolker, (a scientist at Xori, Accelerator) and Charlotte Hubbert, (a Kauffman Fellow at Accelerator).

A little heavy handed with the Accelerator upper echelon. With four employees, including Ms. Warren, Oncofactcor looks more like a post doc and three lab techs doing the bidding of the old white guys. Perhaps Accelerator has grown tired of the failures. They've dipped into their emergency funds to keep up the image of a thriving incubator of biotechnology companies. They've put someone in place whom they can shove around. Was this the vision of the early days of Accelerator?

Worst of all, they are using RNAi to validate their drug targets. The targets are selected with bioinformatics. Both RNAi and bioinformatics have been a disappointment to say the least. They don't have the ability to make the antibodies that are suppose to become their drugs. Instead they will spend their days struggling through the aweful lab experience of trying to get RNAi to work for that brief fleeting moment. From this they will instruct a CRO to make their antibodies. Failure is almost guaranteed. They would be better off waiting for the CRO to send antibodies and use them to validate targets. But then how would a 29 year old bioinformatics immunologist know that?

Will Accelerator one day close its doors? We think it will. It is a Cargo Cult Airport Incubator.

Harry Perry

I want to take a break from trying to figure out the Cargo Cult world and think about something that has worked. This is Harry. He began playing guitar and singing songs for people down on Venice Beach back in 1973. Some people think of him as strange. But if you were to look at his life on paper you would find a stable successful American businessman. He's had the same job since 1973, he leads a healthy lifestyle and he shows up to work everyday. He has no boss, just the hassles of everyday busking on the beach.

As a philosopher, I don't pass judgment on whether or not Harry is an odd fellow. Personally, I like to think about Harry happily blading up and down the boardwalk while I suffer through days of bad science and endless meaningless meetings at multimillion dollar mistakes with sciency names. I do judge cargo cults. Harry is not participating in a cargo cult. He plays you a song and asks you to buy a CD, a shirt or both. Twenty bucks for both. While he plays you can take as many pictures as you like. He has branded himself. He brings his product right to you and you can take it or leave it.

As a biotech employee I have never actually worked at a company that has sold a product. We've brought in millions of dollars but we've never turned that money into a profitable company or product. The only remaining company that I've worked for that hasn't folded is one that makes the claim (among many odd claims) of growing their drug in a more efficient way than the rest of the industry. The claim is false. In fact I don't know of a group of people who know less about the actual manufacturing of such a drug. It seems to me that they took the truth and simply said the opposite. If my experience has taught me anything however, this company will fail. You can only BS for so long.

As I contemplate the future, mine and the cargo cult airports, I can't help but think of Harry. He's outlived 100 billion dollars in biotech waste and hundreds of companies staffed and ran by the brightest minds of our life science scholars. His music isn't the best. He just rolls up to people and plays them a song and asks them to buy a T-shirt. At night he goes for a jog up the coast of that beautiful beach as the sun sets over the hills of Malibu to the north. His future will be to keep on doing his thing til old age takes him out of the game. Our industry will try to get him to hand over some life savings for the pills we make for old people with two months to live, our primary target. But I think Harry will die quick with only a little pain and no regrets.

Everything Is Obvious

If I were to put together a college course on Cargo Cults it would be based on five books:

1) Innumeracy (John Allen Paulos)
2) A Drunkards Walk (Leonard Mlodinow)
3) How to Lie With Statistics (Darrel Huff)
4) Surely You're Joking Mr. Feynman (Richard Feynman
5) Everything Is Obvious, Once You Know the Answer (Duncan J. Watts)

All of the books describe a lot of what Feynman hopes we all get through the course of our educations:

There is one feature I notice that is generally missing in cargo cult science. That is the idea that we all hope you have learned in studying science in school--we never explicitly say what this is, but just hope that you catch on by all the examples of scientific investigation.

Book one asks us to evaluate our relationship to math. Book two is a hilarious view into our random lives. Book three is a classic on how statistics are used to tell any story imaginable. Book four is Feynman telling funny stories from the point of view rarely seen. Book five is new so I'll elaborate on why it's on the list.

The author has an education in physics and engineering. As a profession however, he chose Sociology. Although the field has done a poor job of applying the scientific method, the author believes things are turning around. In his book, Watts explores what we think we know (not just sciency subjects) and he asks us to question that reality. We use common sense to decide what to wear to work versus what to wear to the beach. We use common sense to tell us what to do and we don't really question why. In science we are suppose to ask why.

What this course will do is important. Many in the class will be in the process of preparing for the corporate world. Many of those people will pursue science degrees in their quest to start a biotech company or to climb the ladder at Pfizer. They are bullshitters. Science is going to help them sound sciency. The others in the class however will be nice normal people who just want to learn a little and go into the world where they can contribute, go home and live their lives. They all need to know what the tricks are so that the bullshitters are less confident in bullshitting. It may even put a few bullshitters on the straight and narrow path.

After the course, students may a new framework in which to think. In questioning pharmaceutical executives for example, they might find their thinking more in line with common sense. RNAi is a good example. A Nobel Prize was awarded for describing a process that common sense tells us would be the next big drug platform. Drugs interact with molecules that cause disorders. Eliminating those molecules will prevent the molecules from causing the disorder. It's sciency but it's not science. Science is proving the common sense notion of RNAi to be wrong.

In the field of economics we have common sense notions such as giving the wealthy more tax breaks will lead to more jobs. How is that working out for us? The common sense comment I've heard is, "I never got a job from a poor person." True, but by the same logic, we could make that poor person rich and then he would give you a job. The truth lies somewhere else most likely. Jobs are created... how? We don't know. As a leader in the field you must appeal to the majorities common sense to make them think you do have an answer. Tax breaks for the rich is the answer. It's a common sense solution and it hasn't solved the problem.

The term sciency, by the way, is used in the field of Bullshit. Sciency refers to things that seem scientific by virtue of what scientist is speaking and how scientific they appear to be. Bullshit doesn't rely on lies nor the truth. Bullshit relies on whatever needs to be said or done to achieve the goal. Common sense is the foundation of the process. It's just common sense to listen to scientists when they speak of science. If you don't know what you are talking about you can bullshit your way around by sounding sciency.

The Cargo Cult Science course would also go against the grain of common sense knowledge. The five books are about uncommon, yet learnable knowledge. It would be a science course that isn't very sciency. There would be math but it would come in the form of Innumeracy questions like, "how fast does hair grow in miles per hour?" There would be expert guest speakers. The tests would be to distinguish which ones were bullshitters and which ones were actually who they said they were. Unlike science courses, the CCS course would be fun and accessible to all students interested in looking at the world more objectively. It would prepare you for no occupation but it would help everyone do their job better. When the students leave class and go to the next one, maybe they'll raise their hands and ask more questions.

The Proverbial N-Ray Prism

In a story related to my last, comes the story of the mutated prion that wasn't. We all make mistakes. It is how science deals with them that the keeps us from the truth.

There was a young post-doc who began his career in a laboratory of a prominent scientist. The scientist, not the post-doc, had an idea that needed to be verified. The idea was that a single amino acid substitution could prevent the conformational change of a protein that allegedly led to a brain disorder. There was cloning to be done, assay development, and the usual gels and western blots. Not rocket science but the conclusion, if things worked as expected, would put the world on notice. This was to be a major stepping stone.

At the end of a year the data was in and it all looked kosher. It was time to write up the paper and get the news out. There was only one problem. No one had sequenced the DNA of the clone being used in the study. Prior to submitting their paper the clone was sequenced. The mutation in the amino acid sequence wasn't there. The research was done on a protein that was the same as the controls. A new question arose. How did the data fit the preconceived notion?

How did they see their N-Rays without the prism?

The young post-doc failed in his task. It wasn't his idea but he understood what was expected of him. If he was to make it in the business the results needed to come out a certain way. Like a Sherlock Holmes novel, the final outcome smooths out the leaps of faith and unwarranted assumptions. Science is about genius. At least that is what we think the world expects of us.

Imagine a P.I. testing his post docs by giving them a bias in the form of a protein that is suppose to do something. An assay is provided to give an output signal that will vary from run to run. The protein and its control are in fact the same protein. Will the post-doc point out the precision issues of the assay or will he run the assays until the desired story has been told? In other words, create an N-Ray story. Short, sweet, elegant and false. Provide the measuring tools and bias the outcome. Who uses science to tell the truth? Who uses the bias to tell the story they know will get them them ahead in life?

If you've ever been in a bad job and you needed to get out, you knew better than to tell the next potential employer you want out of a bad situation. You tell the employer that you are looking to advance your career or something along those lines. The truth is not well tolerated in many human endeavors. It is not tolerated in professional science. It is not tolerated in finance or government. We want certain things to be true. Whether or not the prism is there, we want to see N-Rays.

The Drunk Under the Streetlight

A policeman came across a drunk on a dark road scrounging around on the ground under a streetlight.

"What are you doing?"
"Looking for my wallet, I lost it in that ditch over there."
"Why are you looking for it here?"
"The lighting is better."

I'd like to go back to a phage display project because it encompasses the fundamental flaw of science as it is conducted in the biology, medical world. Unlike other sciences, we have a low standard. W are wrong most of the time. The unofficial measurement, wrong 90% of the time, did not raise much protest.

Dr. Nicklin is one of the scientists who worked on the GETRAPL project. The paper is titled:

Development of efficient viral vectors selective for vascular smooth muscle cells.

And it's findings are false. Here is why.

Nicklin et. al. performed phage display as instructed by the kit purchased from New England Biolabs and they came up with a list of peptide sequences. It was decided that a peptide of 7 amino acids would bind to and deliver their DNA to a specific cells type. Once the peptide was discovered it could be used to deliver the viral vector to the cell where the vector will then enter the cell and increase gene therapy activity.

Many assumptions have been made but we will focus on one thing, phage display. The following is the list of peptides the turned up when using the phage display kit.

Peptide Frequency Peptide Frequency Peptide Frequency
AAPMQVT 1 KVTTTRV 1 TARQDSI 1
AKPSPFP 1 LAKHPDS 1 TGHHIFY 1
ALQBKPI 1 LERGPYG 1 THLSRTP 1
AMPYAPR 1 LVPPSGT 1 TLSNYSQ 1
ANMSLLT 1 MGPPSTP 1 TNGLRTA 1
ANSKLSP 1 MPPGYPH 1 TPPQSTG 1
APATSIG 1 NALKFSA 1 TPTIHKT 1
APQPWLM 1 NPFYSLR 1 TPVQQVA 1
ASTQQPT 1 QLTMFPS 1 TQEYRSA 1
DLRIAAS 1 QPNNHAH 1 TQMRQPP 1
EGLPANP 1 QQQHPFK 1 TQPPIRT 1
EYHHYNK 2 SAPERFS 1 TSPIPPK 1
EYTHTPY 1 SFGENSI 1 TTPRFIL 1
FPGKQTT 1 SGSPPSV 1 TTTLRPS 1
GETRAPL 5 SLPDPIH 1 TYATDRR 1
GHSHSHS 1 SLRPSID 1 TYSQSMT 1
GPGPNIS 1 SMPKLIN 1 VKPBTGA 1
GPNQVEW 1 SNAQSMR 1 VLPRASY 1
GSTQPPW 1 SNMAQHR 1 VNPVNTH 1
HLHTIGR 1 SPIRHVH 1 VSAQTRQ 1
HPFILKP 1 SPQLPQL 1 WAPPPAG 1
HPPBVSS 1 SQSPFFP 1 WNLQPPQ 1
HSFPHAP 1 SSHGSLS 1 WPNTYRL 1
HVLWTPP 1 SSQYAHL 1 YHPMSSL 1
IRPPSII 1 SWLPHNA 1 YLKPPGP 1
KLVASNP 1 SYMYKPQ 1

The two peptides of interest recur twice (EYY) and five times (GET). Had the New England Biolabs provided a database of sequences from other panning experiments, Nicklin would have known these sequences are contaminants from the NEB library. The observance of these sequences is to be expected. They are an annoyance and not the holy grail of DNA delivery for gene therapy. What we have here is a limited data set, kit science, and a hope that something shows up. The kits cost $300 dollars each and thus they provide the streetlight that can be used to search for the wallet in the ditch.

The peptide sequences that were "discovered" in this project are the proverbial prism in this modern day N-Ray story.

Once you have "something" the leadership can get to work. You now have a solution and the corrective measure that can be organized and managed. Leadership knows how to organize and manage. They hire team leaders and project managers and directors and even a few white lab coat kids to run the assays in the lab. And they are kids. They will take that useless phage contaminant and make the assays tell the predetermined story. The only question they ever had was how far the bars on their charts would be separated.

Management has found a nice comfortable streetlight. But the wallet is over in the ditch, under water behind a patch of thick weeds 3 feet high. It is hidden in a big way. 20 yards away the leadership stands with their hands in their pockets directing low paid grunts to look harder. Failure in this system is a guarantee. In order to not face failure, hope is put in its place. Hope keeps the project lumbering on and costing countless wasted man-hours and plenty of money.

A recent comment on the state of medical research from Roy Mankovitz.

I have a background­, and publicatio­ns, in the field of rocket science, having designed control systems for planetary landers and deep space probes. As most folks know, we have had a phenomenal record of getting it mostly right.

Well, with respect to science, research is research, but when I finally starting poking around in the area of medical research, spending decades reading and analyzing thousands of studies, I was horrified. It seems they get it mostly wrong.

We do and this is one example. I worked in a different part of the world but I did the same project. The NEB libraries were the same, the cell target was different, the peptide sequences were the same (we found EYHHYNK)and we made the same charts. We used the streetlight approach because it was within our understanding (so we thought) and we found what we wanted. We found the same peptides Nicklin did. Our bosses were satisfied for the time being and kept our project aimlessly moving forward. We too eventually gave up and found new jobs.

Never Confuse Movement With Action

In the book 'Science Business' Gary Pisano begins with the premise that biotechnology has not lived up to its promise. He has ideas and research and conclusions.

I argue that the performance of a science based business, like biotechnology, hinges on how well the sector is organized and managed to deal with the fundamental business problems created by science.

I argue that organizing and managing a cargo cult airport differently results in another cargo cult airport. The science hasn't produced enough drugs so they must shift the science work to someone else. It appears that science is a word that everyone thinks has one meaning. Medical "science", physical "science" cargo cult "science". It's the equivalent of assuming that "God" is understood by all and thus you start a church in Jerusalem with a Catholic priest. It's a good business model. It's a very religious town. You should make a lot of money in the old collection plate over there.

Gary Pisano does a little scientific research himself in his book. Academia and industry claim that industry scientists are the problem. The solution is to sack the staff and shift funding to university and biotech scientists. Gary points out however, that big pharma was no less successful at R&D than small biotech firms or academia.

Universities clearly began to see their science as a buiness. They aggressively patented and sought licensing deals, collaborated with venture capitalists to launch firms, and even began to mve downstream into drug development. Both private enterprises and universities were in the business of science.

So academia has been in the business for quite some time. If industry and academia were to conduct research into finding the successful formula for drug development, they would find that success is random. But then, they need an excuse and a corrective action. Randomness is not an option. Not succeeding is. In fact, it's the most likely outcome, but it is an unsatisfactory answer. No one is going to get at the big pharma money if they tell the leadership that there is no formula for success.

The current theme in industry and academia is to blame the structure of the old ways. Think, cargo cult airport structures such as the man in the watch tower with coconuts over his ears.

A businessman sitting in a room full of other businessmen makes the claim that the in-house science project aren't working. (The cargo planes aren't landing) He claims that this is a cancer and it must be cut out. The anatomy of this real life scenario can be followed by clicking here, then here. The scientists didn't have the freedom to pursue ideas like those in academia do!

A professor at a University sits in a room full of his peers and makes the claim that he is good at science projects that work. Regis Kelly director of the California Institute for Quantitative Biological Research

Academics like myself are great at discovery but are frequently embarrassingly ignorant of the useful applications of our discoveries.

Ahh, arrogance tempered with a dose of humility. He's a genius, but no one knows what to do about it. This is the premise of the alliance. Adacemia = genius Industry = know how. It's a winning formula. The plan is not random. The old ways were flawed, the problem has been identified, and the solution is in place.

Prof. Mark Pepys at the Royal Free and University College Medical School in London, commenting on an alliance with Gilead

We all agree that big pharma is useless at discovering new drugs and has to get its ideas from somewhere else.

Ahh, arrogance tempered with presumptuousness.

So where are we now? Industry believes that there might be some creative restrictions in the corporate world that have hindered "scientists" from innovation. The academia scientists believe that they are good at innovation but they require industries money and "know-how" to translate their genius into drugs. And they are doing it for the good of mankind. Again, Regis Kelly

Alliances with Pharma can bring the knowledge of society needs that we lack. ...it was NOT about the money.

The businessmen are busy forming alliances with old white bearded professors. A call to action or just movement?

The American/Scientists Dream

What is the American Dream? This is what George Carlin has to say about it.

George Carlin and The American Dream

The owners want obedient workers who are just smart enough to run the machines and do the paperwork... It's a big club, and you aint in it!

Let's replace "American" with "Scientists" dream. The concept of obedient workers in science seems to fit. I'm only going to focus on the fate of early stage researchers here because they do the grunt work to create the foundation of the cargo cults.

The leadership will identify what drug targets can be pursued. Each decision is the starting point to a possible billion dollar bet. Ten years might pass between this decision and FDA approval. Think of it as a linear time line, Point A; zero dollars, day one. Point B; one billion dollars, year ten. During this time many things will occur that are classified as work. If you could create a chart of the work and how it is all related you would see how complex it really is. For example, deciding how much drug will be needed for a phase one clinical trial is related to expression level measurements from early stage R&D. This is real work. Somewhere in the chart however, is cargo cult science. This is the area where the billion dollar bet is most vulnerable.

Rather than admit the pitfalls of cargo cult science in the path to a successful drug development, the industry has switched the location of cargo cult work and the financing of this work. Big pharma is getting rid of their in house workers and farming out the early stage work that tells the higher ranking leaders what billion dollar bets they should make. Smaller biotech firms and academia will be taking over that role. Gilead and Yale, for example have a research alliance that will bring corporate sums of profit to the school. The workers now are state university employees or low paid entry level college graduates working at small biotech firms. Big pharma still requires the same obedience and science that conforms to their ten year plan, only it will cost them less. Our scientific dream is now regulated by for-profit pharmaceutical companies.

The employees of the airport must remain obedient workers just smart enough to run the machines do the paperwork. The science that goes into target selection is done by lower ranking people. Final decisions on the billion dollar bet are made by higher ranking people who must also consider making their investors a profit. Once the bet is made, lower ranking people must make the data fit in spite of the rigors of the scientific method. Avenues may open up that could shut a project down. This will effect whether or not you will continue having a job. Cargo cult leaders do not wish to be embarrassed by experiments that point out the foolish premise of their billion dollar bets. Scientists working before and after the billion dollar bet is placed must practice their expertise with diplomacy.

The cargo cults are changing their ways. The scientific dream remains as allusive as the American dream. The man in the watch tower with coconuts over his ears has been moved to the local campus. Universities officials will now look to their natural science colleges as a revenue generating machine on par with the football team. Superstars will arise and move on to high paying jobs in the industry. Both industry and academia run cargo cults so it won't matter much where the superstars take their desk job. It is the lower ranking tribesmen and women who will find it harder and harder to earn a living. The biggest casualty however will be the science that makes some people dream of exciting careers. There will be a lazer like focus on your research. The new science must identify drugable targets and pathways that, when disrupted, lead to the cargo planes landing on the airport owned by your corporate sponsor. Cargo cults dream of the cargo first. They still haven't figured out a way to get it. They've just came up with ways of reducing the cost of running their airports.

Biotech is Back Revisisted

Last year I posted a few times about the 'Biotech is Back' forum here in Seattle.

Seattle’s life sciences industry has been on life support for a few years, but now, for the first time in a long time, biotech has started to show some legit signs of rebirth.

The organizer of this event, Luke Timmerman, posted a very interesting article this week. The title:

Considering a Career in Biotech? How About Trying Computer Science Instead

The comments were also interesting. In them, we get to hear from some of the employees in the field.

As someone who is currently in the biotech industry and have been doing lab work for 10 years, I would not recommend anyone going into biology or life science period. The risk and reward is not worth it and yes, the ladder of success is extremely tough. I agree with this article, change major if you are still in school.

Given the training required and average payout for skills achieved, life sciences / bioengineering is a long, long row to hoe. It is slow, it is expensive, it is glass ceilinged to anyone without a PhD (this includes nearest neighbor industries where PhD’s have fled their serfdom), and it is dominated by a relatively older generation of scientists who do not provide a healthy work structure for young employees. Life Science is an extremely dangerous career path for bright young people, and I encourage them to avoid the field and it’s ever-thirsty vampires.

...be mindful of tailoring your experience to be too protocol specific, in this field having immunohistochemistry experience will only help you get a job doing more immunohistochemistry.

Ironically, on the same webpage, there is a piece by Ken Stuart entitled, "An Investment Opportunity: Training in Biosciences". One reader commented:

I thought it should be noted that the people in positions of leadership in biotech, ala Ken Stuart, can seem detached from the economic reality of what’s happening on the ground. I have to question the sanity of a pushing an training continuum that currently lasts over 12 years, fails to achieve an average pay above 50k at any point, and whose target field is experiencing large funding cuts. That isn’t even taking into account the trainwreck/vacuum of PhD management. In light of the problems already facing life science, Mr. Stuart’s suggestion of starting even earlier seems ludicrous.

We focus on the cargo cult science of biotechnology and hold it accountable for the woes of the field. The leadership can have meetings all day long on how to make more money so they can provide a life long career for young aspiring scientists. Until they understand the concepts explored in CCS and start to weed it out, they will not be successful.

Funny Stories

Lately, the Xconomy folk have been having a hard time coming up with stories to write about the local biotech scene here in Seattle. Since I'm not making a living at it I'd like to share a few stories I've encountered over the years that I think may have something to do with our troubles

There once was a lady who had just receiveed her PhD. During the course of her education she had worked in a lab but she had never dialyzed a protein. We showed her the cassettes and the flotation sponges. The next day we showed up and to our amazement, she had managed to balance the cassettes on top of the sponge, exposed only to the air. The dialysis cassette had not touched the buffer.

Our fermentation scientist (not a PhD) had six 3 liter fermentors. Every two weeks she would set up six runs, usually testing six different methods. When we asked her why she didn't do anything in duplicate she said that it was because she could get more tests done that way. "Ya, but how do you know if the data is reproducible?" "Trust me, it is," she barked at us as she stomped off. Then one day she needed to test only 3 pHs during a particular step. DO EACH ONE TWICE! we begged of her. She did. pH 4 gave very different results, pH 5 both died, and one of the pH 6s gave the best expression. The other pH 6 run died. Conclusion; pH 6 is the best condition but pH 4 could be used in a pinch. pH 5 is lethal.

PS: The six reactors were named after six of the seven dwarfs. Actual conversation: "Which pH 6 run died?" "I think it was Sleepy."

Related story: We had six fifteen liter fermentors. The original process development scientist on the larger fermentors was perusing the fermentation scientists "pH 6" method. The fermentation scientist entered the lab. "What are you doing?" "We're going to try this method at the 15 liter scale." The fermentation scientist snatched the method out of the hands of the process development scientist and stomped out of the room. The process development scientist had to get the method from someone else.

PS: The six 15 liter reactors were named 1, 2... 6.
PSS: The process development scientist was later fired and replaced with an even more experienced scientist. The fermentation scientist was to be a member of his staff. Within the first week of his arrival the he wanted to fire the fermenation scientist. It wasn't allowed. He later left a note reading "Beam me up Scotty, no signs of intelligent life." We never saw him again.

In a Nobel Prize winning lab, they decided to generate antibodies against infectious prions (and not the normal confirmation protein) by denaturing the protein with guanidinium and using phage display technology. As a result of the denaturation, it was impossible to fish out antibodies that adhered to our hopes and dreams. The phage display was done at the Scripps Institute in San Diego. Without testing they sent up numerous samples for western blot analysis. After 3 months it was determined that I (the cargo cult scientist) was incapable of running a proper western blot. In spite of my examples of almost daily western blots using proper antibodies, the job was turned over to another person. They retested my most recent lot. Same result. After a long meeting, my replacement returned to the lab. "How'd it go?" I asked. "You know the step where you boil your sample for 5 minutes prior to running the gel? Well I only boiled for 4 minutes." I responded that I had done that many times and it doesn't really matter. My replacement repeated the work with the 5 minute sample boiling and still obtained the same results. The supervisor was none to happy. She gave us both a dirty look when she saw the same results for the third time.

The ForteBio is a machine that will measure your binding affinity between two proteins. Our ForteBio people tested ten antibodies, 3 times each. In their presentation they listed the 30 results from strongest to weakest binding. A couple of us asked why they had not made a bar chart with the average of each antibody binding affinity and an error bar to show us the deviation of the measurement. The director then took a different tack. On the spot he created an excel spreadsheet and they began using the excel functions to list the 30 antibodies in as many ways as they could think of. Never an average with a deviation measurement. From the strongest to weakest list they selected the one with the first, fifth and 12th strongest binding affinity. It was the best.