A Monster to Fight Our Wars

Let's not pretend that ruthless leaders of other countries are the only ones who use death and destruction to acheive their goals.

Enough

The presidents plan to add more troops in spite of his generals advice is indicative of cargo cult leadership. The concept is that by sending more troops we are fighting harder to achieve victory. The decision was made after extensive meetings. More meetings means better decision making. Get the concept here. More is always better.

A similar form of flawed thinking takes place among pharmaceutical industry scientists. If we can make a molecule bind tighter to its target we say we have a better drug. How tight? They don't know, but they know it needs to be as tight as they can get it.

To me, true science and art are the same. Knowing just how much color to add, how long to hold a note, or how much sky to include in a landscape is part of it. When starting a war you should know what your objectives are so you'll know when you are done. President Bush is not a practicioner of true art and science. He is a cargo cult scientist! He started a war and made a list of 50 bad guys in Iraq that needed to die. Number one on the list will die this weekend. But that airplane carrying peace in the middle east isn't coming. Do we need to kill more leaders? More fighters? Maybe less killing would help.

Obesity

PYY 3-36, one of the many flames along the runway of our cargo cult airport, will live on in 2007.

BOTHELL, Wash., Dec. 21 /PRNewswire-FirstCall/ -- Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK) today reported positive results from a dose ranging study designed to evaluate the pharmacokinetic parameters, appetite, food intake and safety of various doses of Nastech's proprietary PYY(3-36) nasal spray in obese subjects. The study identified doses for a long-term Phase 2 efficacy and safety clinical trial.

Now let's go back in time to see where PYY was in 2004.

86th Annual Meeting of The Endocrine Society (ENDO 2004), New Orleans, LA,

Nasal Peptide YY3-36: Phase 1 Dose Ranging & Safety Studies in Healthy Human Subjects. Download Poster (PDF)

13th European Congress on Obesity, Prague, Czech Republic, May, 2004

Nasal Peptide YY 3-36: Phase 1 Dose Ranging and Safety Study in Healthy Human Subjects. Download Poster (PDF)

So we are back to a point that seemed to be established back in 2004. At that time Nastech was partnered up with Merck to advance PYY. In March of 2006 Merck pulled out of the collaboration after it decided data from a "Preliminary Proof of Concept Study" of the intra-nasal formulation of PYY didn't demonstrate efficacy. Merck didn't want to play The Beer and Pizza Diet so Nastech went back to a happier time, 2004.

From the NSTK website: To date, Nastech has completed three Phase I trials of PYY. These trials have enrolled over 60 subjects and administered in excess of 900 doses in the Nastech PYY program. Results from the PYY Phase I clinical trials indicate the investigational product is safe, well-tolerated and shows evidence of reducing caloric intake, moderating appetite and demonstrating weight loss in human subjects. Unless you ask Merck

Steven C. Quay, M.D., Ph.D., Chairman, President and CEO of Nastech. "These results support a decision (#4 on The Five Dumbest Things On Wallstreet This Week by Colin Barr, 3/3/2006) to advance this program toward a long-term Phase 2 Weight Loss Clinical Trial. With obesity reaching epidemic levels worldwide, the need for a safe and effective product that promotes weight loss has become critically important."

Never ask a drug company CEO if there is a need for a safe and effective product that has become critically important. It's guarenteed that he/she's got one and it works.

A Poem

but they've left us a bit of music
and a spiked show in the corner,
a jigger of scotch, a blue necktie,
a small volume of poems by rimbuaud,
a horse running as if the devil
were twisting his tail
over bluegrass and screaming,
and then,
love again
like a streetcar turning the corner
on time,
the city waiting,
the wine and the flowers,
the water walking across the lake
and summer and winter
and summer and summer
and winter again

--from the poem, " If We Take"
Written by Charles Bukowski

Cargo Cult Leadership

Imagine if there were a Cargo Cult Airport corporation. Imagine the fires along the runway and the man in the tower with coconuts over his ears. Somewhere there would be an office space where higher ranking airport officials conducted the brainwork behind the summoning of the gods. They would probably consume the majority of the tribes "cargo" in the course of their work. The net result of this work would be less cargo for the tribe. Was any work done?

The Legal Services Corporation was set up to provide legal service to the poor. They run on tax money but they have a special status that allows them to operate as an independent non-profit corporation. That means they didn't have to follow government-wide expense guidelines. A recent audit uncovered some egregious expenditures. $13 per person high tea service, $12 bagel breaks, $70 dollar lunches, and $14 Death By Chocolate deserts at board meetings. Then there was the first class airline tickets and the limosine service. Meanwhile poor people in need of legal services were turned away from clinics that we underfunded. Who is helping who here?

Cargo Cult lesson: Work is done when poor people obtain the legal services that the agency was set up to provide. The leaders used the money to provide food services to themselves. Work was not done.

Now to Wall Street. Ah money. People love it but they don't care much for hard work. That's why they created wall street. Put your money into a stock that will turn a dollar into ten while you fly first class to your next LSC meeting! You haven't paid for the flight, your lunch or the ride to the meeting and your own money has made you more money. The rest of America is so dumb for not doing this. But wait, not everyone can do this. If they did there would be no products or services. You have to disallow the riff raff from reaching the highest level of success. Only allow a selected few into this world where work is for suckers.

Check out Goldman Sachs chasm. Investors gave Goldman Sachs boss Lloyd Blankfein a year-end bonus worth an estimated 53.4 million dollars, a record for a Wall Street executive. In all, the bank granted a total of 180 million dollars in bonuses to its top 11 executives. I guess the bank was primariy set up to enrich 11 guys.

Imagine if every construction worker got one square foot for every 1000 they contributed to building. Their own homes would be huge. They could start their own neighborhoods. With that kind of incentive they would work very hard. But they show up every day and earn an hourly salary. If they build a mansion or a shack, they make the same. Somehow they didn't get to write the rules the way the Wall Street bankers did.




Cargo Cult Lesson: Leaders know what people want.

Followers need to know what the leaders want.

The Great Mall of China

Mall of America in Minnasota is huge. The Great Mall of China is three times as large. The Chinese built it prior to securing retailors however. Imagine walking through an American mall where every business had packed up and left. Empty! Now stretch each hall by a factor of ten. That is what this mall looks like. It's empty and it is HUGE! You might say that someone made a HUGE mistake.

This is a good metaphor for biotech. I've mentioned 1616 Eastlake in Seattle. This building is also a large empty space. They built laboratories with no scientists vying for them. No one, so far, has came along to rent them out. Then I've talked about Jeb Bush shelling out hundreds of millions to attract biotech to Florida. The people of Boca Raton authorized 20 million and ended up attracting biotechs golden boys who showed up in Brooks Brothers suits asking for more money. I've mentioned that by 2001 biotech had squandered 40 of the 100 billion invested. And that includes huge profits from Amgen and Genentech.

Biotech is that huge mall in China. Todays top stories from Biospace:

Altus Pharmaceuticals Inc. (ALTU) Enters Into Exclusive Strategic Collaboration With Genentech, Inc. (DNA) To Develop And Commercialize Products For Growth Hormone Deficient Patients; Altus To Receive $30M Upfront Payment And Equity Investment ... More

One of Genentechs first cloned proteins was human growth hormone. What is new here? No product, just a promise.

KOSAN Biosciences, Inc. (KOSN) Announces License Of Motilin Agonist Program To Pfizer Inc. (PFE); Kosan Will Receive Upfront Payment $12.5M; Additional Milestone Payments Up To $250M ... More

No product, just a promise.

Genta Incorporated (GNTA) Cuts More Than A Third Of Its Workforce ... More

No product, no promise.

Northfield Laboratories (NFLD) Blood Substitute Misses Trial Goal ... More

No product, no promise.

Panacos Pharmaceuticals Inc. (PANC) Bevirimat Study Falls Short ... More

No product, no promise.

Janssen, L.P.'s INVEGA(TM) Approved By FDA As New Treatment For Schizophrenia ... More

Eureka! A product. Let's hope it doesn't cause weight gain and diabetes like Zyprexa.

Orexigen Therapeutics, Inc. Files Registration Statement For Proposed Initial Public Offering ... More

No product, just a promise. 90% of all start-ups fail so the promise is weak. Plus their lead candidate is a fat pill. To not come across as a homeopathic type of drug company they throw in the promise of treating CNS disorders. Their research is driven by the obesity market. Some weak science connects their fat pill science with other conditions that can't be better treated with diet and exercise.

Gilead Sciences (Foster City, CA) (GILD) Drug Meets Goal; Company Announces Preliminary Results From Phase III Study of Aztreonam Lysine for Inhalation in Patients With Cystic Fibrosis ... More

No product, but they are getting closer to a product. This is a real product that will help people. Antibiotics work!

You see, I'm not so negative. I ended on a positive note. There is a part of the mall in China that is bustling with people. There is also a part of biotech that has produced useful drugs that help people. My criticisms of the industry come from those who use the good name acquired by honest men and women and use it to line their pockets. People like Jeff Kindler at Pfizer who was an executive at McDonalds prior to his current gig. The era began with scientists but soon became the domain of businessmen. Scientists who couldn't compete in academia hung up their lab coats and started companies. But they didn't have a product, service or a way of obtaining either. To this day they continue to start very expensive companies and/or clinical trials that have no chance of suceeding. They don't know what is needed to succeed. You start with basic science. When it becomes something, you raise the money to advance the drug.

The Lucrative Field of Biotechnology

SBRI, the Seattle Biomedical Research Center. Imagine a world where people live free from the threat of infectious disease. Through leadership in scientific discovery we strive to eliminate the worlds most devestating infectious diseases.

Take Malaria for example. It infects between 300 and 500 million people every year and causes between one and three million deaths annually, mostly among young children in Sub-Saharan Africa. Malaria is not just a disease commonly associated with poverty, but is also a cause of poverty and a major hindrance to economic developmentt.

Sounds like a real problem. The Cargo Cult Scientist has the opportunity to join one of the SBRI groups. Top pay? $37,000.

House payment $2500 split two ways Average house in Seattle 430,000K
= 1250 x 12 months = $15,000

I've got $22,000 left over. But wait, I have to pay taxes. Let's assume 25% 22,000 - 9,300 = $12,700.

oil 1000K
internet $650
phone $550
Student loan $1800
Utilities $900

I'm down to $7,800 and I haven't bought food yet. No car payments or kids thankfully. Gas? Luckily SBRI offers free bus passes. Let's eat conservatively at $75 per week. Okay, I've got $3,900 left. That's $325 per month for gas, haircuts, eating out, baseball games, home improvement and maintainance, car insurance, and on and on..

I'm carving out quite a life here. What will I have to do in return for this opportunity? This job uses molecular biology and functional genomics to investigate the function of the apicoplast in malaria parasites. Working with mice and malaria sounds glamorous.

The guy who works on your car has more experience than most of the researchers working on curing disease. It just doesn't pay and that's why the research doesn't pay off. It's very noble to donate money to non-profit research organizations. Just be aware of how much of it reaches those who work in the laboratories. They ride home on the bus to their studio apartments contemplating new careers. Maybe finding cures for Malaria was a bad idea. Maybe being a school teacher would pay better.

Trust Us, We're Here to Help

For 10 years Eli Lilly has played down the health risks of Zyprexa, its best-selling medication for schizophrenia. Hundreds of internal Lilly documents and e-mail messages among top company managers were collected as part of lawsuits on behalf of mentally ill patients against the company. For example, "unless we come clean on this, it could get much more serious than we might anticipate." Or this one, "Although M.D.’s like objective, educational materials, having our reps provide some with diabetes would further build its association to Zyprexa."

The problem with the drug is that it has been shown to cause substantial weight gain and diabetes. The dilemna for Lilly was that this was their biggest seller, with sales of $4.2 billion last year, when about two million people worldwide took the drug.

What are the scientists saying about Zyprexa? According to an article in the New York Times, "some top psychiatrists say that Zyprexa will continue to be widely used despite its side effects, because it works better than most other antipsychotic medicines in severely ill patients. But others say that Zyprexa appears no more effective overall than other medicines." I guess it's a matter of opinion. But the side effects do not seem to be a matter of opionion. Unless of course you ask Eli Lilly and the FDA. Lilly has never conducted a clinical trial to determine exactly how much Zyprexa raises patients’ diabetes risk.

http://www.nytimes.com/2006/12/17/business/17drug.html?_r=2&oref=slogin&oref=slogin

Does anyone see a trend among corporate types? In order to rise to the top you have to be a certain type of person. These people know the fate of whistle blowers. None of them would dare stop what was happening for fear of ruining their career. What can we do? How can we stop these types of people from making sick people sicker?

Bob Martin

My mom called tonight. She asked me if I'd found a job yet. How is the holiday season going. It was 60 degrees today in Omaha. She said she had a bit of bad news. Her voice was weak. Bob shot himself. He left a note telling Carol that he loved her and that it wasn't her fault. He just couldn't go on any longer. Something was all wrong. She could find him out back.

He's at Creighton Hospital now. He'll be taken off of life support tomorrow. December 16, 2006.

What Did Gilead Do?

Gilead Sciences, Inc. (NASDAQ:GILD) announced today that it has received a subpoena from the United States Attorney's Office in San Francisco requesting documents regarding its marketing and medical education programs for Truvada(R) (emtricitabine and tenofovir disoproxil fumarate), Viread(R) (tenofovir disoproxil fumarate) and Emtriva(R) (emtricitabine). Gilead intends to comply with the U.S. Attorney's subpoena and to cooperate in any related government investigation.

That's all you'll get from the news agencies. The Cargo Cult Scientist will go a little further. They were subpoena'd because they _____ and now they have to explain themselves or they will be ______ by the Feds. You heard it here first!

The Perfect Job

She asked me, "What would be the perfect job for you?" I resorted to my canned answer. I want to work on a drug project that one day makes it to the market and helps people. You throw in some other crap about working for a great team and a great company. You're laid back but not to a fault. Ultimately you want to succeed.

What I really want to do is start a journal. Instead of the usual assortment of unrelated articles I specialize in measuring the measurements. My team of skeptical researchers, who have an admitted bias against the upper echelons of science, devour the journals as they come out. They seek out trends in research tools and they come up with a topic for each new issue of our journal. We begin by trying to reproduce certain experiments. We ultimately make conclusions on the method or methods that are being applied. How hard is the science on a scale of 1 to 100? What pieces of information would be useful to know? Who is using the best equipment and who is taking a short cut? Oh it would be so much fun.

I guess my perfect job would be a thorn in the side of mainstream medical science. At the end of my career there will be a whole new science. The science of method. The study of method. If a scientist does on experiment 3 times and averages the results we'll break down the averages. We'll apply statistics, biology, chemistry, physics and the whole kitchen sink. If you think we are setting ourselves up as the judge and jury of other people without the proper authority you are wrong. The authority is reality. Your credentials won't help you here. You're affiliations will not trump honesty like Imanish Karis did. It's Gonzo science and anything goes.

That is my dream. To start the science of method. The science of negativity will be a subset. A new paradigm is needed for alternative voices to be heard. Modern scientist have made some rather egregious offenses against the good name of science and they need a parody journal to take on their work. I want the job!

The Cycle

The human body goes through a cycle each day. If you really work at it you can train your body to fall asleep at a certain time. You can eat your meals at the same time each day and never be hungry in between. The Cargo Cult Scientist likes to wake up at 6:30 and take a walk around the cemetary next to his house. I wake up, feed the dogs, throw on some warm clothes, wash off an apple and head out the door. It's better than coffee. I'm not always wide awake when I take off but when I get back home I am 100% alert and ready to start whatever it is I do. The first hour of my day is taking care of sleep, food, and exercise. From 7:30 to 12:00 I am free to do whatever I have to do with no desire to eat or climb back into bed.

Eating, sleeping, and exercising should be closely regulated to prevent the kind of deviations that are detrimental to your health. For example, if you are accustomed to eating whenever you feel hungry you will often stop and ask yourself, "am I hungry?" The answer will often be yes and you will eat until you believe you are no longer hungry. If, on the other hand, you eat a bowl of cereal and a piece of fruit for breakfast each morning, you will ask yourself, "am I done eating?" When you see the bowl in the dishwasher and the banana peel in the trash, the answer is yes. If you're still hungry just wait ten minutes. You'll be surprised perhaps but your body cycle will pass by the hunger stage and you will be fine. Maintaining a constant sleep cycle will work in a similar way. The only times you will feel tired will be around the times you go to bed and the time you wake up.

The cycle (that you control) prevents you from feeling tired, bloated and lethargic. The cycle will prevent diabetes, heart disease and high cholesterol. It's a secret that old people know. Young people will find it uncool. But as you grow older you will begin to appreciate more and more the value of fresh air in your lungs. You will sit in your cubicle dreaming of waking up Saturday morning and driving to the mountains for a day of skiing. You'll wake up on a sunny morning with the window open and lay there thinking about all you plan to accomplish that day. All you have to do is keep a few sheduled appointments for eating, sleeping and exercising. In return you will receive the gift of perfect health.

If you are currently fat and/or unhealthy, tighten up your cycle. Think about what you are doing each day. Schedule your eating, exercising and sleeping. Slowly eat healthier, exercise more and get the proper amount of sleep. If you just join a gym you might find that you are hungrier than usual. You might just eat more feeling like you can make up for it at the gym. That is wrong. Each issue must be dealt with individually. Each issue complements the others but none of them can be subsituted for another. If you break down and eat a huge bowl of ice cream after your fish and vegatable dinner, accept it. You still have things to do. Next time you sit down to eat, don't make the same mistake. When you do make a mistake you must think in terms of the weekly schedule. If you only eat one huge bowl of ice cream in a week you will probably be doing better than you did before you started keeping track of your cycle.

Don't do drugs!

NeoPharm NeoPhails

NeoPharm (NEOL) Announces Efficacy Results For Phase 3 PRECISE Trial; Drug Misses Goal In Brain-Cancer Trial; Stock Plunges

WAUKEGAN, Ill.--(BUSINESS WIRE)--NEOPHARM, Inc. (Nasdaq: NEOL - News) today announced that the pivotal Phase 3 PRECISE trial evaluating cintredekin besudotox (IL13-PE38QQR) for the treatment of recurrent glioblastoma multiforme (GBM) did not meet the efficacy endpoint at 215 deaths, which was a statistically significant difference, or separation, in the overall survival curves versus Gliadel Wafer®. "Topline data suggests that cintredekin besudotox, while comparable, was not statistically superior to Gliadel," said Guillermo A. Herrera, President and Chief Executive Officer of NEOPHARM. "We will continue to work with our Scientific Advisory Board and the FDA to determine the best path forward."

Median Survival CB = 36.4 weeks
Median Survival Gliadel = 35.3 weeks

Damn! You take a slice of the population that has 9 months to live and you try to make a profit by extending the worst year of their life. There has got to be some chemical out there that can make this happen.

Good riddance NeoPharm.

Rene Descartes

I'm sure I would be accused of being a complete nattering nabbob of negativity if anyone were to read this blog. From time to time I attempt to offset this possibility by offering up some words of encouragement and understanding by the great thinkers of the scientific revolution. As science began to compete with religion in shaping societies, the philosophy of science had to be explained. Rene Descartes describes his methods below:

I thought the following four [rules] would be enough, provided that I made a firm and constant resolution not to fail even once in the observance of them. The first was never to accept anything as true if I had not evident knowledge of its being so; that is, carefully to avoid precipitancy and prejudice, and to embrace in my judgment only what presented itself to my mind so clearly and distinctly that I had no occasion to doubt it. The second, to divide each problem I examined into as many parts as was feasible, and as was requisite for its better solution. The third, to direct my thoughts in an orderly way; beginning with the simplest objects, those most apt to be known, and ascending little by little, in steps as it were, to the knowledge of the most complex; and establishing an order in thought even when the objects had no natural priority one to another. And the last, to make throughout such complete enumerations and such general surveys that I might be sure of leaving nothing out. These long chains of perfectly simple and easy reasonings by means of which geometers are accustomed to carry out their most difficult demonstrations had led me to fancy that everything that can fall under human knowledge forms a similar sequence; and that so long as we avoid accepting as true what is not so, and always preserve the right order of deduction of one thing from another, there can be nothing too remote to be reached in the end, or to well hidden to be discovered.

Discours de la Méthode

Here he describes my blog:

If you would be a real seeker after truth, you must at least once in your life doubt, as far as possible, all things.

Discours de la Méthode

As consumers of science we must not think of skepticism as a negative thing. It is what some have used to achieve great things. It can be used to overcome the marketing departments of big pharma. It can prevent foolish investments. It leads to the truth and the truth will override the negative path taken.

Tough Week

NicOx SA (NCOX.F) ABPM Trial Shows Favorable Blood Pressure Profile For Naproxcinod; Drug Misses Study Goal
Genta Incorporated (GNTA) Provides Update On Genasense(R) Phase 3 Trial; Leukemia Drug Misses Key Goal, Stock Drops
DOV Pharmaceutical Announces Termination Of License Agreement With Merck & Co., Inc. (MRK)
Coley Pharmaceutical Group Amends Strategic Alliance License Agreement With GlaxoSmithKline (GSK) For VaxImmune(TM) Vaccine Adjuvant ... More
Novacea (NOVC) Says CEO Resigns, Names Interim CEO ... More

Nastech Pharmaceutical Company Inc. (NSTK) Says $15 Million Payment From Procter & Gamble (PG) Deferred

Pfizer Chief Medical Officer Joe Feczko announced that the company was immediately canceling all trials of torcetrapib because it had sharply boosted the death rate of patients in a 15,000 patient trial.

Bayer Pharmaceuticals Corporation (CT) And Onyx Pharmaceuticals, Inc. (ONXX) Release: Phase III Trial Of Nexavar In Patients With Advanced Melanoma Does Not Meet Primary Endpoint

3M Company (MMM) To Cut 400 Headquarters Jobs, Outsource Support Work; 3M Pharmaceuticals (MMM) To Change Name

ImaRx Therapeutics Cancels IPO Due To Market Conditions

ProMetic Life Sciences Inc. (PFSCF.PK) Cancels UK Unit IPO, Says Price Could Rise

Forbes Medi-Tech Inc., a maker of drugs for lowering high cholesterol, said Monday preliminary results from a mid-stage clinical trial of drug candidate FM-VP4 fell short of the company's goals.

ImClone Systems Inc. chief scientific officer Philip Frost resigned Friday, according to a Monday filing with the Securities and Exchange Commission.

Evolutec Ltd Release: Primary Endpoint Not Met In Phase IIb rEV131 Trial In Allergic Rhinitis

Somaxon Pharmaceuticals, Inc. Reports Results From A Clinical Trial Of Oral Nalmefene in Pathological Gambling; Drug Fails In Study

Next week will bring more failure, job cuts, and reduced investment. The times are changing and biotech needs to start working smarter. The big pharmaceutical companies need to buy up well established drug programs. The place to be is somewhere near phase III trials in the lucrative disease areas, cholesterol control, type II diabetes, osteoporosis and pain management.

The message is clear. As a smaller company you must not set out to save the human race from disease. You must save the pharmaceutical giants from their own pending doom. The industry is sick and they need the next Lipitor or Viagra. Americans live very unhealthy lives. You must give them pills to offset their inability to take care of their health. If your drug falls too close to the margin of error you might just miss your clinical trial endpoints or even worse, end up killing people like Pfizer. Think carefully when choosing your pipeline. Do not create new drug classes. Cox-2 inhibitors and CETL inhibitors, although proven dangerous, can still become big sellers. It's tough to decide with so much conflicting data but that is what will keep you going for years to come. Even if you fail, you will have made a buck or two.

As for the investor... we have plenty new drugs for you to invest in. Good ones. Maybe some day you could visit our labs down in the swamps of Georgia. It won't be hard to get around down there. We're purchasing the Brooklyn Bridge and having it shipped down. By the way, could you help us offset the cost of that?

Losing Wars

They say that only six people at the U.S. Embassy in Iraq speak Arabic. Page 60 of the Iraq Study Group report says:

All of our efforts in Iraq, military and civilian, are handicapped by Americans' lack of language and cultural understanding. Our embassy of 1000 has 33 Arabic speakers, just six of whom are at the level of fluency.

The report was 84 pages long. If the Cargo Cult Scientist could add one more recommendation it would be that the staff who wrote this report write another 20 pages on the work being done at the embassy. Who were these arabic speakers? Did they also speak English? Did they work as janitors or translators? Does the work being done at the embassy require a lot of Arabic language interpretation?

This would be a "wax on wax off" type of endeavor. When pursuing something that may seem trivial, you might just stumble upon a big problem. Perhaps the embassador doesn't do anything besides hold dinners and talk about how everyone in the room is going to get rich off of this scuffle. Perhaps we change the embassy mission to have them help us learn more from people in Iraq. How do they feel about the ideas being tossed around in this 84 page solution.

Old men start wars and young men die in them. The old men in this case cannot put an end to this struggle. The enemy is not known. When they get close to a real issue such as the lack of language and cultural understanding, they follow it up with a recommendation that we train people in the language. Languages are not learned that easily, especially when mixing with the locals is a life and death situation.

The war in Iraq suffers from too many old men who do not know their enemy. Too many people on the American side are making decisions for the young people who have to fight an enemy willing to die for their cause. Our leaders are only willing to sacrifice the lives of our young, not their own lives. They don't even take the time to learn from the young men who are dying.

RIP Eden Bioscience

Eden Bioscience, a 12 year old plant biotech company in Bothell Washington has sold the assets of its agricultural-products business to Plant Helath Care for $2.5 million. Eden will retain the right to the technology for sale in the home and garden market.

The company will also be "substantially reducing" its work force from the current number of 35 employees. CEO Rhett Atkens will resign as of Dec. 15, 2006. In the 12 years of their existance they have accumulated a deficit of $116 million. Another net loss of approximately $8 million will be recorded for the first 9 months of 2006.

The Cargo Cult Scientist can remember going to Eden Bioscience in 2004 to look at possible equipment to purchase. From that day on I saw the same scientist who was selling off his equipment walk the trail behind their building. I wondered why he was still there. What were they waiting for? When they held the auction at Encyte Inc. for their final clearance, I saw the scientist again. "Will they be buying new equipment for Eden", I wondered. Now I see that they are tapping out. This is the end.

We do not celebrate the demise of any company here at the Cargo Cult Scientist. We lament their inability to use their science effectively. When a company dies like Eden or Encyte, which was just up the street, more people are left to vie for the handful of jobs that remain. It is not a joyful occasion to see these failures, but it is what we predict based on our understanding of how science is looked at by the industry. They do not know what matters, and they fail. So rest in peace, when in fact you, Eden, do close up the doors and sell off your equipment and your phones. The scavengers will decend upon your old building and place their bids for your stuff. The place will empty and that will be the end. $124 million dollars and counting and that will be the end of it. Another airplane that did not land.

Watch Out for Those Clinical Trials

P&G made a deal. They told Nastech they would pay them 15 million bucks at the end of a phase III trial that was suppose to be completed by 2006. Then P&G ammended their deal. For some reason the trial is now predicted to be completed sometime in the second quarter of 2007. In the meanwhile they are starting another trial. The 15 million dollar payment is now deferred. Nastech stock is down $2.78 or 14.49%.

P&G initiated a biomarker study in patients with low bone mass to measure blood markers of both bone formation and bone resorption. This is the study that was suppose to be completed by 2006 but is now expected to be completed during the second quarter of 2007. An additional Phase II dose ranging study has been added to the clinical development program and is planned to begin later in 2007. Nastech is now saying that they and P&G believe the additional data resulting from the on-going AND planned studies are important for the FDA regulatory pathway.

They should have thought of that before. But then, they didn't have any phase II data to factor in to the decision. Do they know something about the biomarker study? Why is supplimental data needed and why is the milestone payment deferred? Could this be a "biomarker" equivalent in the Biotech investment world? A marker of pending doom is a delayed trial that results in a restructuring of the kind of data to be presented to the FDA as well as the milestone payment schedule. Seems likely.

More Pfizer NewsD

Pfizer losing 13% of its market value on Monday indicates what investors think about the future of this drug company. Pfizer is the largest U.S. drug company yet one little pill has put that in jeapardy. And the pill could never compete with a proper diet and exercise. But Pfizer never cared for a fair fight.

Yesterday we find out that Dr. Trey Sunderland was accused of performing consulting work for the pharmaceutical giant that improperly overlapped with his government duties. Dr. Sunderland faces a maximum of one year in prison and a $100,000 fine. Pfizer is of course a non-human entity completely expected to take any advantage it can get. They face no charges for their complicity.

It just goes to show that the largest drug company in the U.S. cannot win even with huge profit lame duck drugs and NIH scientists in the pockets. All of the ghost writing, doctor buying, cheerleader sales staff, and community killing take over of smaller companies do not guarentee a giant like Pfizer the kinds of profits they are tasked to make. Each quarterly statement must show increasing profits yet Pfizer is facing a future of the exact opposite. Investments will go down. Executives will scramble to avoid accountability. As for the rest of us? I would suggest eating more fruits, vegatables, fish and whole grains. At least once a day go for a walk or a jog. We'll be fine.

Knowing When to Not Prescribe

November 30, 2006 Commenting on torcetrapib/atorvastatin (T/A), Dr. LaMattina said, "We are first-in-class and we intend to remain best-in-class in a category that has the potential to change the face of cardiovascular medicine... To obtain a reliable picture of the overall safety and efficacy profile of T/A, the results of all these studies will need to be analyzed and reviewed together, and this will happen in the context of the American College of Cardiology Meeting in March, 2007."

NEW YORK, Dec. 2 /PRNewswire-FirstCall/ -- Pfizer Inc said that in the interests of patient safety it is stopping all torcetrapib clinical trials and that it has informed the Food and Drug Administration. The Company was informed today that the independent Data Safety Monitoring Board (DSMB) monitoring the ILLUMINATE morbidity and mortality study for torcetrapib recommended terminating the study because of an imbalance of mortality and cardiovascular events."

Dr. Philip Barter, Director of the Heart Research Institute in Australia and Chairman of the Steering Committee overseeing the ILLUMINATE study, said, "Based on all the evidence we have seen regarding torcetrapib and in light of prior study results, we were very surprised by the information received from the DSMB, the only body with access to the unblinded safety data. We believed that the study was coming along as expected, and this new information was totally unexpected and disappointing, given the potential benefits of this drug."

If only there were some way of predicting what a drug will do. Even "prior study results" cannot predict this Hindenburg-esque demise of a drug. Our science is incomplete. Studies cannot be trusted to predict the future. If only there were a way around this.

For the families of those who died, I hope they get more information on the prior studies and how this happened. It was a mistake. Now is the time to learn. The final word comes from the Pfizer CEO:

Pfizer's Chief Executive Officer Jeffrey B. Kindler said, "While the DSMB information we received today was both surprising and disappointing, our focus is on the best interests of patients and making sure all this information is communicated to appropriate medical and regulatory authorities as quickly as possible.

"With regard to our business, we understand the challenge that this represents and we will respond quickly and aggressively to it. It is important to put this information in the context of both our commitment to transform Pfizer and our overall product and financial strength," Mr. Kindler added.

AKTA-vation

As technology progresses it becomes increasingly difficult to keep ones resume packed with the proper buzzwords. Protein purification has a new one, and the word is AKTA. The FPLC (left) and the Explorer (right) are two systems that fall under the title AKTA. ÄKTA purifier systems are part of ÄKTA design, a range of liquid chromatography systems for academic and industrial research laboratories.

For the past ten years the Cargo Cult scientist has purified proteins as the need arose. If a protein was His-tagged I would employ an IMAC column. If it was an IgG molecule I would use a protein-A column. The list is long but anyone should be able to match up a column to a molecule.

The reason I'm talking about this is because I just missed out on a job opportunity because I lacked experience with the AKTA systems. Three years purifying proteins at a Nobel Prize winning lab did not make up for the 3 day training course offered by Phamacia on their AKTA purifying systems. Ten years experience in biotechnology purifying proteins when needed did not equal the 3 day training course. A degree in Biochemistry and an undergraduate research project purifying an enzyme from plant material did not count as protein purification experience. AKTA is where it's at.

It occurs to the Cargo Cult Scientist that the industry is in need of a new paradigm. Those who ponder scientific questions can be put into the category of "creative sciences." Those who deal with the FDA and the equipment utilized to push the drugs out the door can be put into the "applied sciences." The majority of the workers in the latter category need only obtain vocational degrees in the biotech/pharma industry. The benifit to the industry could be a lower cost of labor. They hire a manager who completely understands the science behind chromatography for example. The manager hires a staff of workers from the local community college. This staff understands equipment such as AKTA and they understand the paperwork associated with purifying proteins that will be the active ingredient of a drug.

As for my recent failed attempt at employment, I can only hang my head. I will never possess every single skill required for a job. This too is a beer and pizza diet. If I've used an FPLC, was it AKTA or BioRad? It is perhaps the sound of my voice on the phone that sends the potential employer seeking a way out of the interview. Perhaps my previous pay was too high. Maybe I'm over qualified instead of under. Maybe they've found my blog. Ha!

Whatever the case may be, the Cargo Cult Scientist will forever refer to this lack of equipment experience as an AKTA issue. If you're a photographer and they tell you that you don't have enough Bronica experience (you use a Hasselblad) you have been AKTA-vated. If you can type 100 words a minute, you still must have experience typing form 10WZ4 from Corporation X. Getting a job means being AKTA-vated into a new system. Do you have what it takes?

PhDs and Labs

I saw an ad from Merck with a bunch of middle aged men in women wearing white lab coats and working in a lab. The CEO came on and explained that Merck is now, and always has been, serious about science. It has been my observation however that the scientific landscape of the drug companies is littered with PhDs working out of cubicles, all trying desperately to become an executive. The benifits of such a promotion includes job security and huge bonuses. Very few non-PhDs scientists stand a chance. The non-PhD scientist has a lifetime of reality checking them at every step. If you are going to get into the business you must go all the way with your education. Get a PhD and focus on becoming an executive.

Companies begin when a PhD or MD doctor has an idea. He or she will pump up the idea much like George W. Bush pumped up the war in Iraq. A picture is painted. As we begin to lift the curtain on reality we only expose the things that look like the picture. Those who understand this process will be rewarded and given speaking roles in the company. That means no lab coats. The lab coat people are to be young and easily manipulated. None of them should stick around for long due to the obvious wool being pulled over the eyes of the investors.

PhDs learn how to write grants. They learn how to talk in meetings. It is imperative that a PhD contributes to conversations that are started by those above them. To remain silent would mean that you are not understanding the genius of the higher ranking person. You need that person to advance your career. You must always agree with the higher ranking person but in subtle ways. If they say the earth is flat, you must suggest ways of not driving off the edge. Thus, agreement can be assumed and a suggested advancement of the idea is duely noted. If you are concerned that the false assumption will bite you in the ass further down the road, you are not thinking clearly. You, and all other important people will not be around for the fallout. That's the genius of PhD advancement. You must take on more and more responsibility. When a project destined to fail enters its final stage you make sure it is not high on your list of priorities. You've delegated and your people failed. They may need to be let go. That is the courage of leadership. Some might call it audacity but it does take courage to set up people and convince them that only they can save a project.

When a company fails, the leadership takes what is left over and move on. This is not failure. This is called learning. It takes courage to put yourself at the top of a company chain of command. People expect great profits. You have learned a thing or two when a company goes down. The next company might fail but it won't be your fault. They are expected to fail. You must convince investors that you are the only thing in between certain failure and the big bucks. You'll do everything you can, but there is risk in investments.

And that is the lesson of becoming a successful PhD. You must get where there is no risk. You can make a fortune and never produce one single drug. You can work for one sinking ship after another. Never put yourself in a position where failure can be attributed to something you thought up. Rule number one: Stay out of the lab. Them cells and that DNA can't be told what to do. They are leading all of us and our future as a species. Nevermind that and get yourself into a position of as little risk as possible.

Bukowski On Success

small conversation in the afternoon with John Fante

he said, "I was working in Hollywood when Faulkner was working in Hollywood and he was the worst: he was too drunk to stand up at the end of the afternoon and so I had to help him into a taxi day after day after day.
"but when he left Hollywood, I stayed on, and while I didn't drink like that maybe I should have, I might have had the guts then to follow him and get the hell out of there."
I told him, "you write as well as Faulkner.:
"you mean that?" he asked from the hospital bed, smiling.

Charles Bukowski

New R&D Models

Researching and developing a cargo cult airport is a funny thing. You watch the Allied forces build their airport. How do they light the airstrips without fire and smoke? Perhaps it's important to have that kind of light but you just don't know how to do it. You have to do something.

Pfizer is going to try a new way at conducting R&D.

LA JOLLA, Calif.--(BUSINESS WIRE)--The Scripps Research Institute today announced it has entered into a five year research collaboration with Pfizer Global Research and Development to advance scientific knowledge of uncured diseases and novel ways to treat them, making full use of emerging technologies and resident talent from both organizations. Under the terms of the agreement, Pfizer will pay Scripps Research $100 million over a five year period, during which scientists from Pfizer and the Institute will work together to identify and perform specific projects of mutual interest.

Pfizer, like all other drug companies, is running out of time on the big profit patents. The old R&D methods aren't producing. They sent out talent scouts to find the next way of discovering drugs.

They found that the best researchers are right here in the good o'l U.S.A. God bless them for that.















Eli Lilly seems to be eliminating R&D as a way of pumping up their pipeline. Recently they bought ICOS for 1.2 billion dollars to have full control of the drug Cialis. That's one drug in the bag. The R&D efforts at ICOS are not expected to continue. And there is more.

NEW YORK, Nov 30 (Reuters) - Eli Lilly and Co. (LLY.N: Quote, Profile , Research) said on Thursday it will take a restructuring charge of $100 million to $110 million primarily in the fourth quarter related to its previously announced closing of a research facility in Belgium.

FDA Recommends Celebrex

GAITHERSBURG, Md., Nov 29 (Reuters) - Current data do not show Pfizer Inc.'s (PFE.N: Quote, Profile, Research) pain reliever Celebrex is safe for treating rheumatoid arthritis in children, a U.S. advisory panel narrowly ruled on Wednesday.

WASHINGTON (AFX) - A federal advisory panel recommended that Pfizer Inc's Celebrex should be approved to treat rheumatoid arthritis in children, despite worries about long-term safety of the drug, the Wall Street Journal reported. The US Food and Drug Administration's committee of outside experts voted 15-1 in favour of using Celebrex to treat children with the condition, but said that adverse events must be closely monitored in the long term, the paper said.

Would you give your kid a cox-2 inhibitor?

Eight to Ten Weeks to Live

I missed this one. On November 4th Cell Therapeutics had to halt enrollment in their latest Xyotax clinical trial because of premature deaths among patients taking its experimental cancer drug. The good news is that the deaths did not appear related to any safety problems with Xyotax. There were more deaths in the group receiving Xyotax than another receiving a standard chemotherapy drug.

Here's the crazy part. Most of the deaths have been attributed to disease progression — meaning the advancement of the patient's cancer. The study's patients have advanced lung cancer, with a life expectancy of 8 to 10 weeks.

How much life can be added to a population of people who have 8 to 10 weeks to live. Another statistical gamble has been lost. It could have easily gone the other way. Xyotax has been shown to do nothing. They kept changing the beer and pizza diet and they got burned. But guess what. This isn't the end. Beer and Pizza diets never end!

The company expects to revise the study when it resumes, to focus on women with normal estrogen levels. CTI is claiming earlier Xyotax studies had found a better effect in such women. So if you've got 8 to 10 weeks to live due to lung cancer AND you've got normal estrogen levels, get yourself signed up for this one.

Seattle Biotech Dustbowl

My zero readers will appreciate the futility of this blog. Here we gather from time to time to sort out what is bothering us about our affiliation with the modern world of science. Sometimes it's the executives who profit at the expense of the investors, including those who invest their educations and careers. Sometimes the Cargo Cult Scientist talks to himself about bad science. We talk about how helpless big time journals are against fraud. We talk and talk because there is nothing else to do. There is no work to be had. The futility of this blog is no match for the futility of my job search.

Here in Seattle there has been failure. Many companies have gone out of business leaving hundreds of laboratory workers to compete for a handful of jobs. This is not very well known. Like Boca Raton and Charlotte NC, we want to be known as a biotech hot spot. We want to be the next Boston or San Diego. The Cargo Cult Scientist wants the same thing because he needs a job. We understand that advertising the plight of the skilled labor here will not serve anyones purpose. But no one reads this blog, so we are free to discuss what is happening.

The laws of supply and demand apply here. The supply of workers is far in excess of the demand. Therefore, when a highly skilled technician applies for a protein purification job, he/she may be disqualified because they used a BioRad FPLC as opposed to an HP. A molecular biologist may not make the cut because they have experience with VectorNTI versus DNAsis software. Those in charge of hiring staff have the luxory of finding someone with the exact qualifications. What we are seeing as a result is a readjustment in the creative origins of the industry. We are now selecting for protein purification specialists who have 5 years experience using AKTA as opposed to someone who understands the principles behind all forms of chromatography. Like the dot.com era before us, we may be on our way to a massive clearance to make way for more conservative business models.

And so I ask my zero readers, what should the Cargo Cult Scientist do? This Saturday the CCS will interview for a job washing windows on highrises. I'm excited about it too. I used to sit at a desk writing nonsense about the sillyness of the experiments I did at the bench. Now I could be working daily 300 feet above the city below. But the pay is not the same. In fact, I am back to square one. I know an 18 year old kid who skipped school from February to graduation making the same wage. But I have not worked in 9 months. I have just failed to get an in person interview because my protein purification experience did not include a particular piece of equipment. I guess it's not something a person can learn. Well there are a lot of things I don't know. Unless my last job suddenly becomes available at a different company, I'm finished.

I'll keep trying. In the meanwhile look for me on the 47th floor of the Westin Hotel in downtown Seattle. I'll be the one on the outside of the building.

Profits

I believe I've talked about this before but I wanted to bring it up again to talk about making money in biotech. This is from Red Orbit:

Nov. 2--Senior executives at Icos are in line to receive cash payments worth a combined $67.8 million for selling the company to Eli Lilly, according to a filing Wednesday with the Securities and Exchange Commission.

At the top of the list is Paul Clark, 59, Icos chairman, chief executive and president, who will receive a "golden parachute" worth $23.2 million in severance pay, cashed-out stock options, restricted stock awards and other bonuses for retention and closing the deal.

Others cashing out big include Executive Vice President Gary Wilcox ($8.5 million), Chief Financial Officer Michael Stein ($7.1 million) and Chief Medical Officer David Goodkin ($5.9 million).

Rank-and-file employees of the Bothell-based company will not fare nearly as well.

I've also talked about a major investor, Healthcors plans to vote against the sale of ICOS. But I wanted to talk about another lucky devil, Greg Weaver of SIRNA. SIRNA, you will remember was bought out by Merck for 1.1 billion bucks. Mr. Weaver had left Nastech in 2005 "to pursue other opportunities." He landed the CFO gig at SIRNA six months before the Merck take-over. Damn the luck, he was out on his ass again. How much did he leave with? Four million dollars!

Now here's the hard part of being an executive. His replacement at Nastech came from ICOS. Doh! Phil Ranker left ICOS after being passed over for a promotion. Now he's making good money but nothing makes an executive feel better than a multi-million dollar payday. What did Greg Weaver do right? He was fired from Nastech. What did Phil Ranker do wrong? He quit ICOS.

The Hwang Paper

The very first Cargo Cult Alumnus was Dr. Hwang Woo Suk. He earned this reward by pulling the wool over the eyes of the editors and reviewers of the journal Science. He also gained international fame through the claims he made in his Science papers. And he was lying the whole time. The fraud was discovered not through peer review but because a whistle-blower in Hwang's lab spoke to a South Korean TV station.

In order to correct for their embarrassing inability to tell shit from shinola, the journal appointed a panel to review the review process that led to the incident. The editor of Science, Donald Kennedy, said that the journal accepts the panels major findings. What the panel decided was that this whole thing could have been prevented by extra review procedures. Is anyone seeing a pattern yet?

These panels are populated by reviewers. What good would adding more people and more reviews do? It's like trying to clean off a muddy windshield with a newspaper. No matter how much you scrub you just end up smearing the mud from place to place. More reviews creates more chatter but it doesn't have the power of going into the lab and repeating an experiment. What if this latest panel on the Hwang case would have made the recommendation to have key experiments verified by a non-partial contract research organization? Perhaps such a recommedation would diminish the perceived authority of a scientific panel.

The Science panel said that a risk assessment method should be developed to flag high-visibility papers for further review. Also, authors should specify their individual contributions to a paper, a reform aimed at Hwang's stratagem of allowing another researcher, Dr. Gerald Schatten of the U. of Pittsburgh, to be a lead author of one of the reports even though Schatten had done none of the experiments. The Cargo Cult Scientist would like to point out the no respectable scientist in this age ever does an experiment. They may run a lab where the experiments are done but they are as close to the work as any other co-author whose name is of value to the paper. As for the risk assessment method to be developed, we see another panel being formed in the future.

A scientific paper was once a thing of great beauty. A scientist was once a person who observed nature first hand and offered up explanations that made the world take notice. The ease with which Dr. Hwang hoodwinked this major journal sent out a message. We're doing something wrong. We have a system where highly ambitious people are told that the only way to accomplish there ambitions is to publish papers on how great they are at conducting research. Negative results are not very welcome. The best way to get published is to tell the editors what they want to hear. If, for example, RNAi is popular with a journal you must validate the concept by reportinig how well it knocked down your gene of interest. Failures are just not welcome. How many papers were published last year about RNAi experiments that failed? How many people just couldn't clone a stem cell? Dr. Hwang said he could and he was published. Hmm.

We have a dream here at the CCS. Just as the computer revolutionalized the way offices are ran throughout the world, we believe they can help medical science. A computer is a cold and impersonable entity. It doesn't care of you need to tell your boss that the ELISA assay worked out as planned. It can only report the data it receives. I'll end with a simple example of how this could work.

An ELISA can be developed to the point where all a technician needs to do is add the constituents and read the plate. The plate has a code indicating that the ELISA is, for example, one of three. If one of the ELISAs needs to be thrown out it must be justisfied. The cubicle scientist must understand the system and interpret the data based on the data. NO BEER AND PIZZA DATA HANDLING. If a scientist is forced to design experiment to the point where this will work, the scientist will become a better researcher. Reviewers will have to really understand the designs they are reviewing. Will this ever become a reality? We here at the Cargo Cult Scientist are forming a panel to discuss this very question.

The Bridge

There is a film going around about suicide and the Golden Gate bridge. A documentary producer went to the city of San Francisco and got a permit to film the bridge. What they didn't know was that the producer was going to point a camera at the bridge and sort through the coverage for people jumping to their deaths. The film, called "The Bridge" has some people wondering what this producer is trying to accomplish.

Although I haven't seen it, I am very interested in the concept. You know that over 40 people a year jump off the bridge. You point a camera to capture the last moments of a persons life then you go find out about that person. I suppose you could just look up suicides in the city coroners office but the bridge is special. People come from all over the country, to jump to their deaths from the bridge. Why such a lonely pilgrimage. Is there something they are trying to gain by associating their death with the bridge? Do they feel a kinship to the others who have taken the same route? Does it give them strength? There is something to learn here.

We are interested in gaining understanding into how the human mind works. Mostly however, we are interested in studying how people study things. The makers of "The Bridge" pointed a camera at the bridge and waited. That was the start. What if medical researchers had such a start? We know certain people are predisposed to cancers. Why can't we watch their cells? Why can't we desing methods to identify cells who are ready to jump off "The Bridge"? One way of telling if a cell has lost it's will to live is through aneuploidy. If the number of chromosomes is not complete, then you may be looking at the origin of cancer. It's just a thought. It is unfortunate that most scientists these days observe nature second hand from lab techs.

All of this brings me to an observation I made while watching two college professors discuss whether or not the situation in Iraq could be called a civil war or not. Both men were arrogant old white scholars whose expertise was political science and historical conflicts. Of course they were not willing to call the situation in Iraq a civil war. A reporter who has been there off and on for three years had a different take on the situation. "If this isn't a civil war, I'd hate to be here when one finally breaks out." The reporter laid out some criteria and explained how all of this was taking place. But professors who works in offices thousands of miles away from the sights and sounds of war do not see it the same way. Why believe the guy who isn't there? There is a struggle involving life and death taking place. The best way to understand it is to observe what is happening. Ask the people what they saw. Find out why the thing happened. We're not going to learn anything about this mess listening to politicians and college professors. They talk pretty, but that is what they have learned through observations. They mimic the tones and repeat what they've heard. But they have never been to the bridges where stories begin. Where are the ones who have sat by and watched a story begin, end or just take place for awhile? Why listen to people who are never there?

FDA Questions Pfizers Beer and Pizza Diet

WASHINGTON, Nov 28 (Reuters) - A Pfizer Inc. trial of pain reliever Celebrex has design limitations that raise questions about the drug's effectiveness for treating juvenile rheumatoid arthritis, U.S. Food and Drug Administration staff said in an analysis released on Tuesday.

"Nonetheless, there are limitations to the design of this non-inferiority trial that raise questions about whether it provides adequate evidence of efficacy of celecoxib in juvenile RA," said FDA reviewers. U.S. drug reviewers have questioned Pfizer about data showing the pain reliever Celebrex was as effective as an older drug, naproxen, in treating juvenile rheumatoid arthritis.

The Cargo Cult Scientist has pointed out that Pfizer and the FDA meet tomorrow to talk about the real issues. We wonder why huge pharmaceutical companies and the FDA don't meet more often to avoid these kinds of issues? If a non-inferiority trial was not adequate evidence of efficacy, why did Pfizer do it? Does the FDA not get involved until after a trial has been conducted?

So Much for the $800 Million Pill

From the Washington Drug Letter Online

Nov. 27, 2006
Biotechnology Development Costs Top $1.2 Billion Per Product

The average cost of developing a new therapeutic biotechnology product is more than $1.2 billion, including the costs of drugs that fail in testing and the time associated with bringing these products to market, according to a new study by the Tufts Center for the Study of Drug Development.

Beer and Pizza Diet

A fat man goes to his doctor for a new diet to help him lose weight. The doctor advises him to eat pizza and drink beer for every meal. One month later the fat man returns to the doctor weighing an additional ten pounds. "What kind of beer did you drink? Coors? Well why'd ya do that. You need to drink a microbrew."


You can imagine the endless game the doctor is trying to engage in. One of the things most white lab coat lab techs know is the Beer and Pizza diet. You are given an experiment to do. Most often the instructions are verbal. Sometimes they are sketched out on a chem wipe. Never, never, never (in R&D) are they fully written out. Material and methods sections are written only after the data that was desired has been obtained. It may have taken 10 tries but on the tenth try the data worked out in the cubicle scientists favor.


Is it wrong then to talk only about the tenth experiment? With a Beer and Pizza diet you can easily explain away the first 9. In experiment 1 the lab tech used the wrong brand of sodium chloride. In experiment 2 the cells were used at the wrong confluency. When you get the data that you want, the Beer and Pizza questions needn't be asked. If the data fits, you did the right thing. If it doesn't, you did something wrong.

I once worked with a supervisor who was charged with screening antibodies. When the antibodies failed the western blot test, the questions began. One lab tech was told to repeat a western blot because she had only boiled the protein samples 4 minutes instead of 5. She rolled her eyes and repeated the western. Same result. The supervisor threw up her arms stating that if this tech was foolish enough to boil protein samples for 4 minutes (instead of 5) that there could be a million other things she was doing wrong. One day a good antibody showed up and passed the western blot test. We boiled the samples 4 and 5 minutes and asked the supervisor to point out which were which. She explained that good antibodies sometimes work so well that you cannot see the subtle difference. "Could you show us an example of one that can show the subtle difference." She didn't respond.

Moving higher up the big pharma food chain we have the latest success of Pfizer and Celebrex. Celebrex was the first of a class of new painkillers, called cox-2 inhibitors, approved in December 1998, and it is the last one to remain on the market. Two years after Vioxx was taken off the market and Merck has spent millions defending themselves and their own Beer and Pizza approach to clinical trials, Pfizer is asking the FDA to expand the use of Celebrex. They want to give it to kids as young as 2 who have arthritis. FDA advisers will meet Wednesday to consider the company's request. Why would one cox-2 inhibitor be the cause of so many lawsuits yet another still be on the market and expanding its applications?

Build It and They Will Come, North Carolina Style

Last year Boca Raton FL rejected a request for more money to attract the Scripps Institute to the area. The amount of jobs promised did not seem to justify the investment. A previous investment resulted in bringing in high paid lobbyists who came asking for more money! When it comes to biotechnology, the smartest guys in the room are the ones who know where the real money comes from. It comes from investors, philanthropists, and local governments. It flows into the pockets of executives and into ill conceived R&D programs. If you want some of that money you have to stuff yourself somewhere into the flow. The closer you are to the origin of the flow, the more money you will make and the more opportunities you will have at the next site. Lobbyists, lawyers, CEOs, and aspiring businessmen can now look towards Charlotte NC.

The University of North Carolina plans to spend 29 million dollars a year on billionaire David Murdock’s biotech real estate development venture in Kannapolis. That money is on top of the hundreds of millions in local tax subsidies to help build the research campus.

Currently there are not many biotech companies lining up for lab space at the site. So far, only two companies to be exact. Still, to prepare for the coming blizzard of employment, another major component of the Kannapolis project is a training center run by the N.C. Community College system to prepare workers for what Murdock contends will be thousands of new biotech jobs. Let's add up the reality. We have two companies and a promise of thousands of jobs. But wait, there's more. Clyde Higgs, Castle & Cooke’s vice president of business development, said he has received nearly 60 business plans from companies seeking venture capital for business in medical devices, information technology and drug development. Now we have two companies, a promise of thousands of jobs and 60 business plans that need money.

Do biotech business plans generate money are do they take money? In other words, are local governments investing in biotech or are biotech executives investing in local governments? The Cargo Cult Scientist has posted his observations on the emptiness all around the south Lake Union where Paul Allen is trying to create a Northwestern biotech hub. San Diego is crumbling. When will we see a successful biotech hub? When will the planes land? We've built more than a few Cargo Cult Airports. Each one has kept businessmen and government officials gainfully employed. But they keep coming back asking for more money. When will biotech become an asset and not a liability. If the people of North Carolina think biotech will be an immediate asset, they are wrong. It will be a liability. The question isn't about how much they are paying now. The question they need to ask themselves is how much they will be willing to spend in the next ten to 20 years.

Giving Thanks

It's been a tough year for the Cargo Cult Scientist. He started his blog because he ended his last job. He hasn't found a new job. Money is running out and soon the retirement accounts will have to be emptied to save the house. After the retirements money is gone, the house will have to be sold. But I'm not feeling sorry for myself. I was raised a tough guy. We didn't cry. You are in control of your life. When life hands you lemons you fucking make lemonade!!!

Alright, I am feeling sorry for myself. I have applied for everything you can imagine, not just biotech. I had a phone interview with a company that washes yachts. Each morning you get in your own little boat and hit the various marinas around the area to wash yachts and give tune-ups. I was ready to hang up my career and do some real work for a change. They told me they were worried I'd just leave as soon as I got a biotech offer. The pay started at 11 dollars an hour. Still, I was disappointed by this rejection. I could just see myself heading out in darkness and fog at 7 a.m. I wanted to get out there and smell the Puget Sound and look up at the cars on the I-5 as they crawled along to their miserable jobs. It still hurts. I even wrote them back asking for reconsideration. Nothing.

I believed that biotech needed scientists who knew all about DNA, proteins and how to study them. I'm quite sure the HR lady, who was so smug as I left the building at my last job, had a degree in liberal arts. She once told us how she was going to see to it that "this company becomes a huge success." I'm thinking, why don't you see to it that MetLife pays my dental bill so I don't get sued! We had a little pissing contest before I left. She was trying to show me how much more she knew about the business. "Do you have any experience with in vivo animal cells?" "Do you mean mammalian cells inside an animal?" We just stared at each other. Prior to hearing "in vivo animal cells" I had no reason to dislike her. On my way out the door, with my box of belongings we smiled at each other under a cloud of mutual resentment.

I made a mistake. I entered a field where PhDs are made into supervisors instead of talented and experienced researchers. I've had to explain DNA chromatograms to senior level scientists who list molecular biology as part of their expertise. I've had to explain the development of an ELISA assay to the director of QA. His development procedures usually began by purchasing the assay from Amersham then changing a buffer or two. I've spent 6 months trying to get difficult concepts into the heads of cubicled science people only to start all over when the lawyer joined in on the meetings. Now it's all over. The industry only wants younger kids to come in and do the lab work. They're cheaper. Anyone can do the work.

I'll give thanks when and if they let this crash test dummy out of this car that is speeding towards the wall. I continue to play the game of hide and seek a living wage. Until then I am thankful to the New Belgium Brewery in Fort Collins Colorado for making Fat Tire beer. I may not make any money but I can't go back to Pabst Blue Ribbon. I haven't sunk that far yet.

A New Cargo Cult

Again, from Biospace:

PALO ALTO, Calif.--(BUSINESS WIRE)--Intradigm Corporation, a privately held biotechnology drug development company focused on the discovery and development of RNA interference (RNAi) therapeutics for the treatment of diseases with unmet medical needs, has achieved several significant corporate developments. These developments encompass strengthening the senior management team, completing a $16 million Series A financing, and establishing new research and drug development facilities in Palo Alto, CA.

Intradigm was formed in 2000 to develop proprietary nucleic acid delivery technology. The fundamental platform of Intradigm's technology is a ligand-targeted nanoparticle system that is capable of systemic delivery of multiple RNAi molecules targeting different genes.

"The discovery that RNAi can silence gene expression is a major scientific breakthrough, and has led to numerous developments towards the use of this technology as a treatment modality," said Dr. Mohammad Azab, CEO of Intradigm. "However, the translation of that discovery to a therapeutic drug is hampered by lack of effective delivery systems. Intradigm is developing such a system and we intend to aggressively pursue the realization of the therapeutic promise of RNAi using our technology."

New research and drug development facilities in Palo Alto, CA

From the Cargo Cult Scientist:

The company started in 2000, before RNAi had been discovered. When they say, "nucleic acid delivery technology," they are side stepping the fact that they were a gene therapy company. The long suffering gene therepy scientists were given a reprieve with RNAi. They simply morphed into RNAi specialists. Gene therapy, RNAi, what's the difference? It's all nucleic acid magic.

Welcome to the Caro Cults of this blog Intradigm. I await your contributions to this fascinating area of biotechnology. We'll be keeping track of your progress.

RNAi Mice

From Biospace:

Artemis Pharmaceuticals GmbH, Cologne announced today that it has signed a research agreement with Merck & Co., Inc. to construct a large number of shRNA interference genetically engineered mouse models (1) for the in vivo functional analysis of selected disease related genes. The agreement represents a significant initiative to undertake a large-scale approach to gene function analysis using shRNA knock down in genetically engineered mice as models (2) for human biology.

Under the terms of the agreement, Artemis will generate genetically engineered shRNAi "knock down" mouse models (3) for Merck using Artemis' proprietary, optimized and fully integrated vector construction, ES cell transfection and inducible RNAi technology (4). Merck will provide selected shRNA sequences that correspond to mouse genes that may also play a central role in human diseases. Artemis will use its technologies to achieve constitutive as well as inducible functional down-regulation of the expression of the gene targets provided by Merck (5).

Artemis is the first company to have developed a robust methodology for the controlled induction of shRNA based gene knock down (6) in adult mice. This inducible system permits the down-regulation of a selected target gene to be turned on and off thereby more closely modeling the dosing of a pharmacologic inhibitor. The generation time for such a mouse model at Artemis is only four months.

From Cargo Cult Scientist:

What are the six highlighted groups of words saying?

1. shRNA interference genetically engineered mouse models The mice generate siRNA that KOs a gene?

2. using shRNA knock down in genetically engineered mice The mice have been engineered to produce a constant amount of a certain gene product that can be KOd by adding siRNA?

3. genetically engineered shRNAi "knock down" mouse models The model constituatively produces siRNA and it's target?

4. inducible shRNAi mouse models The model constituatively produces siRNA and it's target?

5. constitutive as well as inducible functional down-regulation of the expression of the gene targets They can regulate the expression of a gene target and thus better measure the effects of siRNA that will be delivered much in the way the siRNA drug will be delivered in humans?

6. controlled induction of shRNA based gene knock down They can control the induction of the siRNA that has been engineered into the mouse?

I went to the Artemis website to figure this out.

First they clone in the siRNA sequence that will knock out an endogenous gene product. They are using Taqman to measure mRNA levels. Let's assume that this is the accepted method of measuring RNAi knock down. Wouldn't a better control be to not induce the RNAi in one mouse and induce it in another. That way you are comparing the effects of RNAi and not two genetically different mice. According to Artemis:

Using a reporter system, we have demonstrated that in our system constitutive RNAi knock down of over 80% can be achieved in almost all tissues of the body. Of what protein?
This knock down has been shown to be stable over at least 25 weeks and is inheritable into the next generation. At 80% KO strength?
Development of a system to efficiently produce RNAi knock down mice within 4 months. Why does it take less time than making other genetically altered mice?
We have shown that RNAi-based constitutive knock down of endogenous genes can reproduce the phenotype of the corresponding conventional gene KO. Such as???

We'd all like to have mice that make any protein you want and that could easily be measured. Add something you think will kill it off and start piling up the data. It's not real. Time will tell. This goes on the list of Cargo Cult Science projects. Too many questions have been left unanswered. It has all of the signs. We've got measurements that hitherto have been unable to nail down. We've got data on an unknown gene but claims of 80% KO in all tissues. And we've got the one chart with two bars, one taller than the other. It's a dead give away. Stay tuned.