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Saturday, September 30, 2006

Build It and They Will Come

Paul Allen had an idea. He wanted to turn the south Lake Union area of Seattle into a biotech hub. It is a beautiful part of Seattle and what could better compliment such a place than a large population of well paid professionals? Oh sure, there'd be a lot of science geeks but look what Microsoft has done for the Northwest. You'd be surprised how much more attractive a geek becomes with a Porche and the kind of women they attract.

Yesterday I was riding my bike in the South Lake Union area. There is a building that has been there for at least three years. I noticed this building when I first arrived up here 3 years ago. The building was completely empty. "Lab Space For Rent", the sign said. I was excited by the thought of having jobs popping up right there where I lived. I wouldn't have to drive all the way out to Bothell to ply my trade. Paul Allen was putting in high rise apartments and upscale retail space. This was going to be nice, I thought. In the past three years I interveiwed at two seperate biotech companies that set up shop in that building. The first company had two employees. the president and his lab worker, and one small laboratory. At the next company there were said to have been 5 employees. I talked with three, one of whom claimed only to work there Monday through Thursday. On Friday he worked at another company in the building. He said he wouldn't have taken the job if it had been for just the one company. Hmm. So when I rode past this building yesterday I stopped and looked up to see how they were all doing.

The building is quite large. There are approximately 8 floors on a nearly entire city block space. The companies that I interviewed with are part of Leroy Hoods Accelerator Corporation. So far there are 5 companies taking up approximately 1% of the total space in the building. Fred Hutch takes up space on the top floor. There is a coffee shop and a failing fitness center on the ground floor. The rest of the building remains empty. The building will serve as a measuring stick for biotech in the area. It will serve as a measuring stick for Paul Allens dream of turning the Lake Union area into a biotech hub. As I've mentioned, the main renter in the building is the Accelerator Corp. All of their labs are on the north end of the building on the second floor. This is the shortest side of the building. Still, as I rode along looking in, I saw one empty lab after another. Each lab was new, clean, gas and air on each bench, and empty. Eventually I passsed the Accelerator companies. They comprised about four of the little lab spaces.

The company that is truly making money off of this business venture is called BNB construction. They were busy outfitting more of the interior space. Will it be lab space? Are the buildings owners contemplating renting to non-biotech companies? It's hard to tell. Very little news comes from the dreamers of the biotech hub. "Build it and they will come", does not seem to be happening here. Major players like Leroy Hood may have seen his best days long ago. The big companies like Amgen and Genentech tend to build their own buildings. Whose left?

The investment capital is one factor in making this work. They have done their part. What the dreamers were counting on was the brain power of UW, Fred Hutch and the other institutes around such as Leroy Hoods Institute for Systems Biology. Where are all of the big ideas? Why can't a huge investment and all of this brain power generate more than a few companies taking up four small lab spaces? And these companies are not generating any buzz! Were these companies set up like plastic decoys? Was Leroy Hood brought in as a duck call? No one is talking about it up here. In a previous post I talked about an article written back in 2004 exposing the woes of biotech. Billions and billions had been lost at this point. I've talked about the woes of city officials in Boca Raton Florida who shelled out millions to attract biotech to the area and ended up with a bunch of suit and tie people asking for more money.

Here in Seattle we have seen failure. Targeted Genetics gave up its cystic fibrosis gene therapy treatment. Icos gave up its emphysema and chronic bronchitis research after four years. Corixa dropped a lymphoma drug that was 15 years in the making. Cell Therapeutics was sued by investors after it's lead candidate failed to reach it's clinical trial endpoints. Dendreon, Targeted Genetics, Cell Therapeutics all laid off a majority of their R&D teams last year. Excyte, NeoRx, Corixa, Cell Tech, all closed up shop. But if you look at the web sites you will see management staffs with the big degrees. You will see boards of directors and scientific advisory boards with more degrees. None of these people will ever talk to the lowly laboratory scientist who will have to develop the drugs that the big brains have decided must be developed. The big brains will build companies. They will get the money. They will do everything but go into the lab and see if it was all worth it. The end results have been seen over and over again. But it's starting to lose it's luster. The buildings are empty. The workers are leaving for other careers. The country still has it's lust for drugs but the dreamers are starting to see their folly.

Wednesday, September 27, 2006

The Web Site

The Cargo Cults of biotechnology need to be looked into. What are the forms that must be followed in order to convince everyone that you have a legitimate business? Remember what Feynman said about the cargo cults in his speech. He described the cargo cult airports and said, "They're doing everything right. The form is perfect. It looks exactly the way it looked before. But it doesn't work. No airplanes land."

Today I want to describe "the form" of a biotech cargo cult. What does every company have to set up so that it looks like a proper biotech company.

You start with a website. The website describes the company (Cargo Cult). Each website must have:

A mission statement: A brief one or two sentence statement that cuts to the core of why the company exists. Companies have recently moved away from claimiing to be world leaders in their field since everyone was doing it. Now the statements must explain to the investor what the main focus of the company is. Medivations claim is to identify early stage technologies and develop them efficiently. They of course use more words but a statement should show some pizazz.

About Us: This section of the website introduces everyone to the management team, the board of directors, and the scientific advisory team. They also describe the origin of the company here. It is important to have a large collection of PhDs and M.D.s who worked for other bigger companies in important positions. The board members must be on several boards of important companies or institutions. Listing failed companies does not seem to hurt since most companies fail.

Pipeline: There should be at least 4 drugs in the pipeline. The more the merrier. Each drug is put on a chart that lists it's indication under its name. To the right is a bar that indicates the stage of the drug development. At the top of the page is the stages from pre-clinial to FDA approval. Follow the bar up to the top of the page to see how close the drug is from approval. That is to say, how close the airplanes are to the airport.

Investors: Most biotech companies will have only investors as customers. They are buying a dream that one day there will be a product. In order to deal with the grumblings of the investors as the products fail to come through as promised, they have a special site to keep them abreast of what is happening. You also put up the ticker for the investor here.

News: The news section is a place to say whatever you want to say about the progress of the company. Most companies will use this site to announce upcoming conference calls, clinical trial results and scientific meetings where they will be presenting. It's important to post something at least once a month lest people think nothing is going on at your company. This is the beauty of scientific conferences. It provides cubicle scientists to get out and talk about what they think is happening in their labs and clinical trials.

The web page is a window for the world to see the airport. There is no actual footage of the airplanes landing but all of the forms are there to make one believe that they are on the way. If you have chosen science as your career, and you find yourself working at one of these airports, you will soon start to see what cannot and will not be shown on the website. You will find out at the company meetings that the siRNA experiment has no negative controls. You will see the 300 mice sitting in formaldahyde, abandoned due to the obvious lack of efficacy of the drug spoken of so fondly on the pipeline section of the web page.

The website is the first form. I haven't even mentioned the smattering of white lab coat wearing people on the website or the pictures of scientific equipment. This will be discussed in the next post where I will describe the physical setting of the biotech company. I will describe the buildings that house them and the people who mill about inside. I will describe... the airports.

Monday, September 25, 2006

The Predictive Powers

To set the stage for the analysis of Medivations Cargo Cult I would like to talk about the predictive powers of science. It is important to know when someone has a disease. We have used science to predict the paths our health can take. This provides us with a measuring stick when we try and alter the outcomes of disease in our favor.

What is the path of Alzheimers? We know that it occurs later in life. Kids don't get Alzheimers. Pfizer and Eisai have a drug called Aricept (donezipil) that showed some effectiveness in delaying the onset of Alzheimer's. From Derek Lowes' blog, In The Pipeline: Aricept is a cholinesterase inhibitor, part of the first wave of compounds that were brought in as Alzheimer's therapies. Inhibiting cholinesterase increases the amount of a key neurotransmitter (acetylcholine) that hangs around in the synapse, which should, in theory, lead to stronger signaling between neurons.

Medivations drug Dimebon began as an antihistamine but was later reported to bind to cholinesterase. As I've discussed before in the Cargo Cult Scientist, biotech companies will associate binding with inhibiting a protein function and curing a disease. But does it really bind specifically to cholinesterase? Medivation claims that it binds to two validated Alzheimers targets, cholinesterase and NMDA. We also need to know how well it inhibits the enzyme and how does that effect the onset of Alzheimers?

Ultimately, we are only interested in the onset of Alzheiimers. Aricept is currently sold for this very purpose. Now we have a positive control to compare Dimebon. According to Derek Lowe, "We don't understand neurotransmission well enough to be sure that we're doing much good just by turning up synaptic signaling. To add to the problem, the relevant cholinergic neurons are among those being damaged by Alzheimer's itself, so the drug's therapeutic target is slowly disappearing. That's why the cholinesterase inhibitors are recommended for very early stages of Alzheimer's, and are considered useless for late stages of the disease."

It is hard to evaluate the recent success of the phase II trials of Dimebon. Cargo Cult Science does not report data. They report their interpretations of the data they select from the research. The methods employed in this trial were to have doctors give opinions or psuedoscientific Alzheimers measurements. The real science has yet to be done in understandinig the human brain. What breaks down? Why do some people get the disease and others not? Many questions remain to be answered. What Medivation has done has been to jump into a muddy pond (along with Pfizer) only to emerge from time to time to tell us how crystal clear everything is below the surface. Why should we question them?

Science is an abstract concept. When assessing the work of scientific pursuits you must admit that you are partly judging the science and partly judging the scientists. You must, in this case, discuss the motivations of the people reporting the work. You must also discuss the way the data is coming in. Dimebon binds to two AD targets. While the additional binding target may look like a bonus, it tells us that the molecule is not target specific. We may wish to see the data including the negative controls, the methods of measurements and so on. When it comes to the phase two trial we will want to know what the doses were. Who did the analysis? This abstract concept of science must begin with soft questions such as these. Then we move on to the real methods of understanding.

Aricept answers one of these first "soft questions". Again, Derek Lowe:

Pfizer went out as early as possible, out to before patients had even shown signs of Alzheimer's at all. It appears that Aricept therapy helped slow the onset of the disease, among those who developed it at all. Problem is, the effect wasn't large, and after three years any benefit had completely disappeared. The placebo-treated Alzheimer's patients were in the same shape as the ones who had been getting Aricept all along.

You wouldn't know all this from a quick look at most of the popular press, though, which went with New Breakthrough headlines like "Drug is First to Delay Onslaught of Alzheimer's." (Science, on the other hand, went with "Study Questions Efficacy of Popular Alzheimer's Treatments", which is more like it.) I'm in the same camp, and it's the same one as the editorial from the issue of the New England Journal of Medicine where the study appeared. Aricept, the journal said, "may offer some benefit, but any such benefit is quite limited and apparently transient" Try turning that into something that'll make you sit past the commercial break. . .

Pfizer has even tested their drug in people without Alzheimers and found that it increases memory function. Derek Lowe reported way back in 2002 that they ran a study that demonstrated a slight improvement in memory when people used their cholinesterase. So what does all this mean for the future of Medivation? There is already a cholinesterase on the market. It's effect has been questioned in the big time journals. But the investors are the ones who have to be impressed. This airplane does not have to land in order for the staff at Medivation to have a good run, make some money before they move on to the next "project".

That's enough for one day. We have gone over some of the background of Dimebon. We have touched on the sociology of biotechnology professionals. They have taken an antihistamine and reinvented it as a cholinestase inhibitor class drug. (they are also testing this drug for Huntington disease!) We have looked into a similar drug that is on the market. Using the predictive powers of science we can assume that Dimebon will show a slight improvement due to some creative work in the clinical trial department at Medivation. We here at the Cargo Cult Scientist do not believe that any airplanes from the cholinesterase airlines have yet arrived. Aricept tells us something. The history of Dimebon tells us something. Let's see what is next.

Thursday, September 21, 2006

Making Money While Prior to Airplane Arrival Time

I'm going to pick on Medivation because they are new and claiming success. The cargo this cult is hoping to get is a therapy for Alzheimers. The drug is called Dimebon(TM), and it has a 20-year record of human use and demonstrated efficacy in animal studies of both Alzheimer's disease (AD) and Huntington's disease (HD). It began in Russia as an antihistamine drug and graduated to AD and HD applications.

The drug itself seems odd. For the Cargo Cult Scientists purposes let's just assume that it is a widget. What it does or doesn't do is, for now, not important. This post is about the Cargo Cult that is biotechnology. Medivation has followed all of the biotech forms. These include:

Step One: Get a CEO and a board together. Quite often the CEO will be a person with an M.D. and a PhD. That means they piled on the education only to find themselves sitting at a desk and working as an MBA. In spite of the heaps of degrees the CEO has not developed any products. He buys them in the form of "licensing technology".

Board members must come with impressive credentials. Whenever something happens around them they work hard to get their names attached to the acheivement. This goes on the website to impress the investors.

Step Two: Get money! Here is where the science educations come in handy. The investors most often do not understand the science terms being used in the presentations. They can thus be easily hoodwinked. They don't want to appear stupid. If the scientist says he's got a cure for a disease he must. What matters to the investor is the business plan and the profit potential.

Step Three: Hire a staff. Most important members will be the CFO, the COO and other executives. The CSO must be a "team player". Science can be a tough customer. The CSO must be able to work around it and sell the company line. The financial and business people will do what they do but they will soon come to identify themselves as biotech people. The science staff will be around to give off the illusion of having an R&D program. Investors want to know that there is more than one egg in the basket. This covers that fear. PhD scientists will be stationed in cubicles and people with bachelor degrees or less will work in the lab. The web site will be covered with pictures of these people. Occasionally the CEO or a PhD scientist will borrow a white lab coat and have his or her picture taken in the lab for PR purposes.

Step Four: Sell the potential. Most biotech companies will never make a dime. They will take a lot of money out of the pockets of the investors never to be seen again. At all times a company most be presenting to some organization that matters. These presentations and the quarterly company meetings will predominate the press releases. The idea is to keep people minds off of the science and the results. Eventually there will be an announcement that a drug trial is going forward or being ended. Most often they will end. These are tough days for the executives but that's why they demand the high salaries. It's a stressful job.

Step Five: Seek out bigger partners. Sign deals that include milestone payments. Hundreds of millions can be made without ever getting a drug on the market if you can play it right.

The day to day practices involve keeping investors pacified. All companies will eventually have investor relations departments. The stock price is the ball that everyone must keep their eyes on. This also keeps the eyes away from the science.

That's it for today. The next post will discuss the day the planes are expected to arrive. This is a day that all executives must understand and be ready for. There are ways of talking and tones that need to be perfected so that failure does not catch you off gaurd. Stay tuned.

P.S. I didn't forget about Medivation. I will go into details of the above steps using Medivation as my Cargo Cult. Trust me, this will work.

Cargo Cults Red Flag

Ever wonder how so many drugs fail their big trials? It begins with the scientific foundation that goes into the development of a drug. This "foundation" is the softest and most manipulated area of corporate science. Generally you will find higher paid PhD scientists who work in cubicles bullying low paid white lab coat wearing individuals around. When you move a drug further along you run into tougher customers. Human trials for example can be hard to work around. No one wants to flat out fabricate the data. There are tricks to work around less than stellar data. If that fails you make up an excuse such as a placebo response being unexpected. But how honest people with no stake in the outcome of a drug company predict what will fail and what might just make it?

I am going to predict a failure. The company name is Medivation, Inc. and they have a drug to treat Alzheimer's disease. The first red flag is of course a Biotech company pursueing Alzheimers disease. You have a patient population that has just lost their mind. The only way to tell if your drug is helping them is to invent some endpoints that you think are important. You certainly won't be able to ask the patient if they're feeling better. Medivation today is announcing that they have successfully demonstrated efficacy in not one but all five efficacy endpoints they went after. What are the endpoints?

The primary endpoint was the Alzheimer's Disease Assessment Scale-cognition (ADAS) The key secondary efficacy endpoint, the Clinical Global Impression of Change (CGIC). Dimebon-treated patients also achieved statistically significant improvement (p less than 0.01) compared with placebo patients on all three of the other secondary efficacy endpoints - the Activities of Daily Living, the Neuropsychiatric Inventory and the Mini Mental State Examination.

It's curious that they did so well. Were they really double blinded? Has no one else come this close? Is there a positive control to compare this drug to? There certainly has been no shortage of corporate R&D projects on the disease. Have we finally seen something to throw millions of dollars at or do we throw that kind of money around with little provocation?

If you're going to lie you should throw in some failure. It looks better that way. Now I'm not saying that Medivation is lying. They do however employ some unusual measurements which have worked out in their favor. The measurements were taken in support of a Phase 2 clinical study of 183 patients with mild to moderate Alzheimer's disease conducted at 11 sites in Russia. Russia?

A Dr. Hung explains that, ""The Phase 2 data that we are announcing today are an important step in validating Medivation's business model. We secured our first equity financing less than two years ago, and to date have used less than $20 million in funding our operations. With that investment of time and cash, we have not only generated positive results in a large Phase 2 Alzheimer's disease trial, but also initiated new development programs in Huntington's disease and hormone-refractory prostate cancer, both of which are scheduled to enter the clinic in the next three quarters. We also remain committed to finding new technologies to reach our targeted portfolio of four to six programs."

It's not so much that they've developed an effective treatment for Alzheimers, but that they have validated a business model. They most assuredly saved money by using Russian doctors and their patients in their clinical trials. Could this indicate a cheapness in the research? Again, were these truly double blind tests? Based on my biases against Russians and Biotechnology I'm going to say that this is all bullshit. It's a non-scientific hunch but I think I spot a Cargo Cult. Not only are they successfully treating Alzheimers but they are also taking on Huntingtons and prostrate cancer. That's too much science for the money. Cargo Cult!

Failed Airports

From Biospace:

Sept. 20 /PRNewswire-FirstCall/ - NUCRYST Pharmaceuticals Corp. (NASDAQ: NCST - TSX: NCS) today announced preliminary top line results from the company's Phase 2 clinical trial examining the safety and efficacy of drug candidate, NPI 32101 in a topical cream formulation, in children and adolescents with atopic dermatitis. NPI 32101 is NUCRYST's patented active pharmaceutical ingredient.

Treatment success was defined as "total clearance" or "almost total clearance" of disease signs. An intent-to-treat analysis with 387 patients demonstrated no significant difference in disease clearance among the three treatment groups.

Analysis of the data demonstrated that 35.8% of patients receiving 2% NPI 32101 cream, 35.1% of patients receiving 1% NPI 32101 cream and 34.6% of patients receiving placebo cream achieved success in almost clearing or totally clearing their disease after 12 weeks of treatment. The success rates of both 2% and 1% NPI 32101 creams were statistically identical to that of the placebo. Although the study did not meet its primary efficacy endpoint, the higher than expected placebo response rate may have made it difficult to discern efficacy of NPI 32101. A more detailed analysis of the study is underway.

"NUCRYST is continuing to analyze data from this study so that we can evaluate options for our atopic dermatitis program with a complete understanding of the study results," said Scott H. Gillis, President & CEO, NUCRYST Pharmaceuticals. "Based on our preclinical results in a variety of in vitro and in vivo models and the consistently favorable safety data generated in all clinical studies, we believe that NPI 32101 has the potential to treat various inflammatory and infectious conditions. Therefore, we plan to continue our efforts to develop NPI 32101 for a variety of disease conditions."

This is science in the Pharmaceutical world. If at first you don't succeed try try again. Sheesh! Note the "higher than expected response rate" in the placebo group. Expectations trump actual data.

Wednesday, September 20, 2006


In order to keep yourself honest you should admit your biases. I, for example, am biased against the drug industry. I believe that once they decide to put a drug in their pipeline they are no longer intested in the scientific method. The only thing that will stop them from moving the drug toward the market is if the safety data spells trouble or if a larger firm collaborates with a smaller company and decides not to go ahead with the deal. In many cases the smaller company will continue to pursue the drug because they have already made a heavy investment and they are not ready to give up yet.

I have that bias. I'm not alone however. There are people out there who think negative thoughts about the drug industry. There are those at the laboratory level, clinical trial level, and drug sales level. You name an aspect of the industry and there are detractors who are biased against the practices that they have witnessed first hand. The question is whether or not these biases are blinding us from the good that drug companies do. Not everyone is bad.

Here is a list of people whom I admire for speaking out against the industry (or at least are trying to be heard).

Me: Shy and afraid of being heard and put in the spotlight. Lab scientist who thinks that survival of the fittest in the drug business goes to those who have no relationship with the scientific method.

Gary Taubes and John Crewdson: Science writers who cover contraversial science issues.

Stewart and Feder: Former NIH scientists who transformed their careers into scientific bullshit detectives

Kathleen Slattery-Moschkau: Former drug sales person who exposed the drug industrys sales practices via a fictional film and a documentary. In the fictional film a drug sales lady explains that she gets doctors to prescribe her companys medicine. She has a degree in science... political science.

John Abramson M.D.: Actual medical doctor who became so fed up with the way medicine was being corrupted by the drug industry he wrote a book called "Overdosed America".

James Randi: This is my hero. Former magician who saw psychics and other charlatans making a killing off of cheap tricks that any amateur magician could easily explain. He is a true scientist. Most PhD scientists couldn't hold a candle to his experimental designs.

The bloggers; Pharma Gossip, Michael Lascelles, Aubrey Blumsohn, Peter Rost: All dedicated to acknowledging the Cargo Cult science of large corporations.

Alright, I'll stop there. There are plenty who are of the same mind as me. But if science were a political system, we have to admit that we are but one party. There are very honest people who disagree about things. AIDS research has people on both sides of that debate who are apparently serious about their convictions. Who is right? The Cargo Cult Scientist would like to see HIV studied more as a virus and less as a world wide enemy. Even amongst members of the same party, differences of opinion will arise. Since science is practiced by human beings we must admit that our biases are a source of strength but also a source of folly. It is a tricky rope to walk but one we must walk. This is where we find allies and foes alike. This is where we identify ourselves with ideas that others had before they entered our minds. How could we be wrong when others have the same thoughts? Biases are undeniable.

Bias is not something that we want shoved in our faces when we are argueing a point however. If you oppose the way Halliburton is billing the tax payers for the war you want to make sure that people don't think you are just sore about Bush and the war. If you know a right winger with the same opinion towards Halliburton you will be sure to point out that two people with different biases towards the war can have the same opinion towards the issue of Halliburtons billing policies. We use the biases of others against them so why would we suspect that others won't hold ours against us. The thing to do is to admit it right from the start and to explain how they do not affect what we think is happening. Whether or not I believe in Stan Prusiners prion theories does not have any affect on a mad cows demise from TSE.

The modern day politician wants you to believe that his bias is protecting the American people from evil doers. The modern day scientist wants you to believe that his bias is getting to the truth. We here at the Cargo Cult Scientist believe that a persons main bias is themselves. Their career goals, their family and their security interests dictate what biases they will have. There is nothing wrong with that as long as you are aware of what your biases are. Remember, biases can help and they can hurt. Don't ignore them, at least not to yourself.

Friday, September 15, 2006

Help Wanted

A lot of laboratory jobs that are offered require you to perform things that haven't been succesfully performed on a regular basis within the business. They want the technician to do what the PhD population has yet to clearly define. For example:

The successful candidate will function as part of an interdisciplinary team to characterize and validate proteins and monoclonal antibodies for the XXXXX pipeline.

What does "characterize and validate" mean? It probably means that you will have to go into the laboratory and provide charts and graphs that demonstrate that a protein or antibody interacts with the molecules that they are suppose to and that it results in certain endpoints. So what the company is asking you to do is to come in and close the deal. They've come up with some proteins that they have managed to build a company around or at least an R&D program. You'd think they would have characterized and validated these before they sold someone on investing on it. Let's see how they interpret characterize and validate.

Strong experience with development and implementation of a variety of mammalian cell based assays such as proliferation, soft agar and apoptosis is required.

They have already determined that the proteins will be affecting cell proliferation. That's why they want you to run these assays. But how many times will you need to do it? If they have developed the proteins shouldn't the assays also be developed? The only help they need is someone who knows how to operate a pipette. Apoptosis assays can be purchased. What experience do you need other than the ability to run new assays as they go on the market?

Extensive experience with mammalian cell culture, transfections, use of retroviruses, gene knock down tools and basic protein analysis required.

Okay, if you've got cell based assay experience, you've done some cell culture. Transfections are not rocket science. Retroviruses? Gene knock down tool probably means siRNA. Basic protein analysis is as difficult as any of the other assays. Again, they need only a person who has used a pipette before.

Experience with monoclonal antibody characterization using cell biology tools and use of fluorescence microscope strongly preferred.

How does experience with monoclonal antibody characterization differ from basic protein analysis? Does this differ from the other requirements such as mammalian cell culture and apoptosis assays? One would assume that the monoclonal antibody binds to a known target and it has been well characterized. What this company wants is someone who will come in and produce all of the charts and graphs necessary to make thier antibody drugs work. The problem is that it is up to the antibodies to do the work. The assays and other techniques should already be known. All the company needs is a lab tech. Train the tech on the specific assays and wait for the data to come. But here is the problem. They don't know what the charts and graphs will look like. They don't know the form of the evidence that will make their antibody drug a success. They want a 40 thousand dollar a year science geek, without a PhD to come in and close the deal with nature.

Corporate scientists do not design experiments. They hire lab techs and vaguely direct the research by insisting on certain assays and other methods. What you will not find is a chart that needs to be filled in. For example, if I wanted someone to run a "basic protein analysis" BCA to determine a protein concentration I would require the protocol be followed exactly, duplicate standards and various dilutions of the unknown to ensure that one of the values falls within the linear range of the standards. I would not have to ask if the standards were prepared in duplicate or just ran in duplicate because I would be designing the experiment that I am asking someone else to run. Biotech companies do not design experiments in this manner. They design job descriptions and sit back and wait for the technician to do everything else for them.

Pipelines thoughout the business are empty. They may have some spiders and rats creeping around in the rusty water of the pipes but they are not pumping out what they were meant to pump out. Useful drugs require experimental design. This does not mean designing a job description.

Thursday, September 14, 2006

I Have a Dream

I have a fantasy where I win the lottery for 150 million bucks. That's enough for my little dream job to take place. I start a science journal. Only this one comes equiped with a laboratory. That's why I need 150 million dollars. I'm not messing around here. What the journal does is accept papers that we think are falsifiable. In addition to being falsifiable, the consequences of either true or false outcomes are of no matter to us. What matters is where the truth lies.

Like Feynman said in Cargo Cult Science, "If you've made up your mind to test a theory, or you want to explain some idea, you should always decide to publish it whichever way it comes out. If we only publish results of a certain kind, we can make the argument look good. We must publish BOTH kinds of results. "

The trick of this new science journal is to have no conflicts of interest in either outcome. We must publish the results and base our reputation on how many things we get right. Unlike the modern day journals who rely on peer review, we will rely on that lab that is a part of the journal. Peer review is an unscientific method. This journal would be the first of it's kind. It's purpose would be to shame the major journals into returning to a more scientific method of reporting science. Here is how we will deviate from the status quo.

When a paper is recieved it will be reviewed for falsifiable conclusions. The methods that are reported will be written up for experimentation within our lab. If someone reports a western blot of a hamster brain for example, we will get the brain material and every other material used in the western and we will run the very same gel. Only the falsifiable experiments will count towards the final review. Once the experiments have been repeated the review will begin. In the journal you will first read the paper that is under the gun. Next there will be 3 separate reviews. Each review will go over the data obtained from repeating the experiments. They will break down the conclusions and discuss how their data was interpreted with relation to the original author. The final review will be purely philisophical. Was the experimental design Cargo Cult or was it good science? Were the methods hard science or soft? Was there ample room for statistics to come into play? In essance we will be testing the tests and analysing the analysis. In the end we will simplify the conclusions down to the shortest explanation of their significance.

We will seek out the simplicity of things. It's easy to make complicated arguements that others find too cumbersome to question. We will seek out the simplest of questions that most people think have been fully answered. What is a protein. Can we measure it? Can we measure gene expression? What are the micro-environments inside a cell and how do they regulate gene expression. There are so many questions to answer. The dream I have of this journal is to take on basic questions, slowly and methodically, and to get to the best possible answer we can get to. We will never be able to know the whole truth. Again, quoting Feynman, "We can't define anything precisely. If we attempt to, we get into that paralysis of thought that comes to philosophers… one saying to the other: "you don't know what you are talking about!". The second one says: "what do you mean by talking? What do you mean by you? What do you mean by know?" But we can get as close to it as is humanly possible. The most important aspect of the process will be to take our hopes and dreams out of the picture. There must be no conflicts of interest. No egos to shatter. No careers to worry about. The only thing that matters will be the truth.

Friday, September 08, 2006

Anyone Got Anything To Share?

So far this blog has mostly been a diary of thoughts I have regarding the philosophy of science. Having worked in a science related field I have been surprised at how unscientific most people are, including most scientists. I use this blog to try and understand what motivates someone to be dishonest or sloppy with the facts or whatever their deviations from the truth are. I am willing to bet that there are hundreds of others like me. They work in laboratories. The work for people who do not work in laboratories. They have to use unforgiving scientific equipment to tell the tall tales predetermined by their superiors. They have as much to add to this blog as I do. It's a Dilbert blog that needs some new stories.

My hope is that one day someone who works in a laboratory will read this blog and it will hit them like a ton of bricks. They will find this as a forum to share their stories. We could write up all of the silliness without the risk of being caught by the pharma industry. Outsiders could read about how science is conducted by those who otherwise get lots of respect. This is a place to air out the dirty laundry of the science religion and those who rank the highest.

What we care about here most is the truth. If a full professor of mathematics from MIT states that 2 plus 2 equals 5 and a mentally challenged mongoloid from West Viginia says that it equals 4, we say that the mongoloid is correct. The truth is the only thing that matters here. Unlike the scientific journals, we don't care about your credentials. We want to hear your your story of the truth or the deviation from the truth. Always, the truth must be lurking someone nearby.

If you're a disgruntled postdoc, an undervalued associate, or any other form of lab staff in the bio business (academia or industry), tell us your story. Did David Baltimore try to ruin your career? Did John Darsee make you look unproductive? Talk about it. You're among friends here. We know how airplanes work and where they come from. We know about your airport managers as well. Let's tell funny stories about them and try and make sense of it.

Wednesday, September 06, 2006

The Airplanes That Never Came

If you want evidence of a Cargo Cult in Biotechnology, you need only google a companys name. You'll end up with some old and new information. Go to the old and see what they were up to a few years back. Then try and find out what happened to some of those projects. You'll find out that the attempt at finding a cure or therapy disappeared into thin air. You'll wonder how it ended but there will be no press release on a cancelled project, at those at the early stages. Just once I'd like to see something like:

Company X has ended it's early stage research and development project to find a cure of Alzheimers because we couldn't make any sense of the data the technicians were providing us. We wanted them to find something that binds to Amyloid beta and then breaks up Amyloid plaques. Turns out things aren't that simple and we realized we were in over our heads. We have switched to easier projects.

When you're in the business of making money on stock performance press releases like that won't work.

Here is an example of what I'm talking about with regards to googling a company to find some projects that disappeared into thin air.

November 8, 2004

Company X announced that the Company has entered into separate agreements with two undisclosed research partners to evaluate the development of proprietary formulations for the nasal delivery of compounds useful for the treatment of type 2 diabetes and Alzheimer's disease.

Here it is September 6, 2006 and there is no drug in the pipeline for Alzheimers disease. Having worked for this company however, I can share a little secret with you. Back in 2004 we had a scientist from the Mayo clinic come and give us a talk. He seemed annoyed at the group of young kids sitting around the conference table. Were we suppose to be colleagues of this grey haired scientist at such a renowned research center? Towards the end of his talk he started discussing the work people do with Amyloid beta.

"Some people think you can just find something that binds to the protein and that will cure the disease. Why? Has someone got a reference that indicates that the protein is the cause of the Alzheimers? Has someone shown that destroying these plaques cures the disease?"

He went on and described our research approach almost exactly. Of course he was talking about the stupidest way of "researching" Alzheimers. Later the people working on Amyloid beta just sort of moved on to other things and never came back to the Amyloid beta work.

The questions I can't find answers to are:

Who were the two undisclosed research partners?
Were the details of the project written up in any form ever?
How did it end?

These questions are basically asking about the airplanes that were promised. We like to hear about airplanes full of cargo coming to an airport near us. But when they don't come, how do the leaders handle the PR? It obviously gets swept under the rug. How do they do it without as little recognition as possible?

Tuesday, September 05, 2006

Why Is It Allowed?

I was thinking about Dr. Blumsohns problem with Procter and Gambel. They gave him some data from a clinical trial. He was to analyze the data and provide his results to the company. They would then use this as evidence that their drug works. The problem was that they didn't give him the codes so that he could complete his analysis. I wanted to think of an analogy that could describe the case. For the life of me I cannot understand why everyone in the world, including non-scientists, doesn't see what is wrong here. Why isn't this an open and shut case where P&G apologizes and fires the staff who tried to pull this trick on the world?

I thought about the O.J. Simpson murder trial. You label blood samples. Some come from the crime scene. Others come from suspects. Others come from people who were known to be at the crime scence such as the victims and the investigators. You then analyze the blood and put the matches together. You still don't have anything. What makes this process useful is knowing the codes. Let's say you've got samples 2 and 17 matching up. You reveal the codes and you find sample two came from the crime scene and sample 17 coming from a volentary blood draw from O.J. Simpson who is claiming to have not been at the scene.

The technical aspects of matching DNA samples to each other doesn't say anything. What matters here (what brings the cargo) is that a suspect now has a piece of evidence linking him to the scene of the crime. He says he wasn't there. His DNA says he was.

Back to Dr. Blumsohn. Is this similar to his case? He has the data but not the codes. He finds very little differences between any of the subject groups. Perhaps the drug did not do much better than the placebo. Perhaps the placebo worked a little better. I'm going to assume that DNA profiling is much more reliable than data analysis from a clinical trial. None the less, you need to know what group was what in order to really finish the job.

Dr. Blumsohn also accuses P&G of cherry picking from the data to make up a story different than the one he would have told. How would P&G know what data they needed to weed out? They would have had to know what the codes were. If group A was known as the drug group and it was similar to Group B, the placebo group, then these two groups would have to have some data thrown out. What is the desired outcome? That determines what data stays and what data goes. You can't pull this scam without the knowledge of the codes. And this is what Dr. Blumsohn was trying to get so that he could practice something a little different, known as science. Scams and science require in depth knowledge of the truth.

They wanted Dr. Blumsohn to remain blind. Why isn't this obvious? Why is it allowed? My guess is that there are mortgages to be paid, braces that are needed and so on. These transgressions are thought of as white lies. One data point here and there are not big deal. The little details matter however. It should not be allowed. P&G and Sheffield University should be ashamed. They have a new Cargo Cult ceremony. They've covered the eyes of those standing along the runway. They are making airplane noises. The lack of cargo can be easily explained away, because that is what they who make airplane noises are also skilled at. But the let one of the commoners stand along the runway with his eyes open. He saw what they do and he is trying to share with us what is happening. We still can't see. We heard the airplanes. We know the cargo will be here soon. People are getting ready for it. Isn't that proof enough?