I wanted to go with a more positive note today. Then I saw a report on a 400 million dollar planning experiment. In 1997 the Washington Department of Transportation set out to replace the 520 bridge that connects Seattle to the opposite side of Lake Washington. The old bridge remains in place. I couldn't go on with a positive attitude. A few gems from the research into the spending showed projections of starting construction in 2002 and 2004. Tolls were set and never put in place. Starting later this year (???) a toll system will be put in place with scanners and varying tolls based on the time of day. Out of towners will be billed (unbeknownst to them) by taking a photo of their license plate and sending them their bill for 5 dollars in the mail. I couldn't believe how badly local officials can do their job and get away with it. We are shutting schools down out here to save sums of money far less than 400 million dollars.
This is what a Cargo Cult does. They plan, they design, they talk and the use up resources with almost no regard to the actual goal. The cargo in this case is a bigger bridge that will ease congestion during peak travel times.
Allow me to digress and mention the "positive" story I was going to write about. It is related to the 400 million dollar bridge plan. I recently went to New England Biolabs (NEB) in Ipswich MA. NEB sells restriction enzymes for cloning DNA. They are a rare biotech company because they make money. They also use a portion of the money on environmental causes. For example, when planning to build their headquarters, they ran into the obstacle of three 200 year old Birch trees. They could have easily chopped them down. They spent over a million dollars extra to save the trees. The company is owned by one man, who at the age of 80 goes to work everyday in his own lab. The running of the company has been turned over to the younger generation. The old man conducts science in hopes of finding new ways of extracting energy from things like lobster shells.
The old man must have had a plan. He did not cash in and sell the company. As a result, the old man did not have to argue with investors over whether or not he could shell out the million plus to save three old trees. The employees could relax and do their jobs without fear of shutting down. Research tools were developed to help users use the products, free of charge. The plan was to make NEB synonymous with molecular biology while respecting employees/customers and our world.
What then can we say about the 400 million dollar bridge plan? There is a lot that can be learned from the investment. The problem however, is that the lessons are considered negative. We want to be positive. We want a bigger bridge. We don't want to sit around bickering about who wasted what and why we didn't stop them. Yet that is important to know.
It is the study of the Cargo Cult. The cargo in this case is a bigger bridge. After 13 years and 400 million dollars, we still have the same old bridge. But that is not all we have. We have 13 years of plans. You can research this. Surely something went wrong. It is not negative to want to find out why. The bridge planning leadership will accuse the Cargo Cult Scientists of seeking to judge and blame, but a science merely seeks the truth.
So I am left wondering two things: 1) Why did New England Biolabs succeed? 2) Why did WSDOT fail? There are concrete logical practices that could explain both.
Tuesday, March 22, 2011
Sunday, March 20, 2011
BMS and California
Corporations don't commit crimes, their people do.
Bristol Meyer Squibb is full of criminals. They paid $515 million in 2007 to settle allegations by the federal government and other states that it used a kickback scheme to defraud the Medicare and Medicaid insurance programs. Now the state of California is going after them. Apparently it is illegal to bribe doctors to get them to prescribe your pills. The article makes the claim that BMS had paid out of 15,000 bribes in a six year period.
Let us not leave out the blame to be placed directly on the medical profession. Doctors don't want to sit down with their patients and explain the relationship between diet and exercise. They deal with the relationship between sickness and pills.
Bristol Meyer Squibb is full of criminals. They paid $515 million in 2007 to settle allegations by the federal government and other states that it used a kickback scheme to defraud the Medicare and Medicaid insurance programs. Now the state of California is going after them. Apparently it is illegal to bribe doctors to get them to prescribe your pills. The article makes the claim that BMS had paid out of 15,000 bribes in a six year period.
Let us not leave out the blame to be placed directly on the medical profession. Doctors don't want to sit down with their patients and explain the relationship between diet and exercise. They deal with the relationship between sickness and pills.
Monday, March 14, 2011
Cargo Cult Journals
I've come across a most interesting contributor to the idea that science is simply the pursuit of the truth. Bruce G. Charlton is a Professor of Theoretical Medicine, University of Buckingham, and was formerly the editor of the journal Medical Hypothesis. He was fired from his position after the journal was taken over by Elsevier and Dr. Charlton had decided to publish a paper from Peter Duesburg.
One of the great threats to science (the truth) comes from the demands of a large group of human beings. Many will engage in the competition to be in charge of the group. Elsevier executives must know what the corporate identity is and what they can do to preserve it. Mentioning Peter Duesburg is taboo within Elsevier so they had to remove Dr. Charlton from his position as editor. The next generation of scientists are also effected. They rely on being published by Elsevier journals. They too mustn't upset the non-living entity known as Elsevier. Their livelihoods depend upon understanding what is acceptable. The most successful will pursue what is not just acceptable, but what is favorable.
I'm going to explore some of the ideas (as I interpret them) presented by Dr. Charlton in greater detail later. The moral of todays post is that we are facing a monopoly in science. Executives at a large corporation are making decisions that should be left up to the talent. Elsevier took control of a journal and control of editorial decision making. Warren Buffet doesn't even operate this way. Buffet researches companies and buys the good ones. He leaves the management in place and lets them do their job. Science needs to learn this lesson. Smaller groups of humans means more groups of leadership. More groups of leadership assures a diversity of ideas. Since scientists are good at convincing people of both good and bad ideas, diversity is needed to get at the truth. When leadership is consolidated into one group we have lost a battle.
We here at the CCS dream of a journal of negative results. By asking scientists to write about things that did not work, we can get a fresh perspective on things like RNAi.
In their actions towards Medical Hypotheses, the publishers (Reed-Elsevier - who publish about 20 percent of the world scholarly journals, and a higher proportion of those journals with high impact in their fields) decided what went into the scholarly literature and what did not.
One of the great threats to science (the truth) comes from the demands of a large group of human beings. Many will engage in the competition to be in charge of the group. Elsevier executives must know what the corporate identity is and what they can do to preserve it. Mentioning Peter Duesburg is taboo within Elsevier so they had to remove Dr. Charlton from his position as editor. The next generation of scientists are also effected. They rely on being published by Elsevier journals. They too mustn't upset the non-living entity known as Elsevier. Their livelihoods depend upon understanding what is acceptable. The most successful will pursue what is not just acceptable, but what is favorable.
I'm going to explore some of the ideas (as I interpret them) presented by Dr. Charlton in greater detail later. The moral of todays post is that we are facing a monopoly in science. Executives at a large corporation are making decisions that should be left up to the talent. Elsevier took control of a journal and control of editorial decision making. Warren Buffet doesn't even operate this way. Buffet researches companies and buys the good ones. He leaves the management in place and lets them do their job. Science needs to learn this lesson. Smaller groups of humans means more groups of leadership. More groups of leadership assures a diversity of ideas. Since scientists are good at convincing people of both good and bad ideas, diversity is needed to get at the truth. When leadership is consolidated into one group we have lost a battle.
We here at the CCS dream of a journal of negative results. By asking scientists to write about things that did not work, we can get a fresh perspective on things like RNAi.
Saturday, March 12, 2011
Another Dendreon Exec Departs
What is going on at Dendreon? Last year Dendreon lost a high ranking executive with no explanation. Varun Nanda, the Senior Vice President of Global Commercial Operations was said to be an arrogant egotistical a-hole but when did that ever work against an exec? Now they are losing the Chief Scientific Officer and co-founder of the company, David Urdal.
Why would a high ranking member of Dendreon leave when they are just getting started? Because he wants to hang out with his grandkids? Do these types of people even take off work to watch their own kids grow up?
Something is wrong at Dendreon. They have a drug that has marginal efficacy. A lot of work has to go into bullshitting your way through life. Maybe he has grown tired of it and wants to take a rest.
Anyone who has talked to me for more than two minutes knows that I have become bewitched, bewildered and bedazzled with the arrival of our first grandchild last April. The same month that the FDA brought us into a new era of cancer treatment with the approval of Provenge, my daughter brought the Urdal family into the next generation with the birth of my granddaughter – Ava. I look forward to seeing the world through her eyes and the eyes of the grandson we expect to see in June.”
“I am now in my sixteenth year with Dendreon and what an extraordinary journey it has been – the first autologous cellular immunotherapy approved by the FDA! What an achievement and what a pleasure it is to be a member of such a truly extraordinary team – the Dendreon team – as we won the high achievement of Provenge approval. We are just getting started.
Why would a high ranking member of Dendreon leave when they are just getting started? Because he wants to hang out with his grandkids? Do these types of people even take off work to watch their own kids grow up?
Something is wrong at Dendreon. They have a drug that has marginal efficacy. A lot of work has to go into bullshitting your way through life. Maybe he has grown tired of it and wants to take a rest.
Wednesday, March 09, 2011
Improving Early Stage Research
The NIH has a new one billion dollar plan to help the cargo cults get more airplanes to land on their runways. It seems that about 1 out of every 10,000 molecules selected to become drugs ever make it. And the biopharmaceutical research sector invested an estimated $65.3 billion to discover and develop new medicines in 2009. How does all of that money and brilliant science result in such failure?
The National Center for Advancing Translational Sciences has been created to fix the problem. According to NIH director Francis Collins, the goal is to develop old discarded drug development programs far enough to interest industry in finishing the job. The government is going to help the pharmaceutical industry get more drugs into the market. I guess they have some data that shows a correlation between the number of drug approvals with an improvement in the health of the American people.
To be fair, they are claiming to take on disease indications that are not profitable to big pharma. When the NIH scientists get to a certain stage, big pharma will take over. There will be a smooth tech transfer and drugs will be made available to help people.
It seems like the government is working for the drug companies. The new center will be in the same position as a small biotech company, offering up possible drug programs for pharmaceutical companies. How will this effect the claim of one molecule in ten thousand becoming a drug? Will government scientists improve early stage research or will they take the financial hit for some of the failures?
The National Center for Advancing Translational Sciences has been created to fix the problem. According to NIH director Francis Collins, the goal is to develop old discarded drug development programs far enough to interest industry in finishing the job. The government is going to help the pharmaceutical industry get more drugs into the market. I guess they have some data that shows a correlation between the number of drug approvals with an improvement in the health of the American people.
To be fair, they are claiming to take on disease indications that are not profitable to big pharma. When the NIH scientists get to a certain stage, big pharma will take over. There will be a smooth tech transfer and drugs will be made available to help people.
It seems like the government is working for the drug companies. The new center will be in the same position as a small biotech company, offering up possible drug programs for pharmaceutical companies. How will this effect the claim of one molecule in ten thousand becoming a drug? Will government scientists improve early stage research or will they take the financial hit for some of the failures?
Monday, March 07, 2011
Me Talk Pretty One Day
After listening to a few panel discussions from this years WBBA Life Science Innovation Northwest, it became painfully obvious that an interest in science is of little use in the business of biotech. Ironically, neither is there much discussion on how to make investors money. The individuals speaking at the meetings were already making good livings off of other peoples money. Investors can make money in a number of ways, including betting against a public company. But the business of biotechnology has many different kinds of companies and business models. Innovation Northwest was a group of Cargo Cult leaders talking about ways in which to keep the gravy train rolling regardless of scientific progress.
Imagine if you will, the very first Innovation Northwest meeting 11 years ago. The individuals speaking at those meetings were all leaders of the field. They spoke of how to pursue an IPO, how to get initial funding, and all of the money ideas of the time. This years meeting was no different, only the ways of getting money have changed. It is much more difficult to get money because whatever they were talking about 11 years ago didn't go very well. One thing that the CCS takes great interest is in the ways people talk about things that aren't so. The tones of certainty that were used 11 years ago were probably the same as those used this year. It is a tone of certainty that makes you believe that what you are hearing is about progress. But is it?
James Randi spent his early career as a magician, tricking people into believing things that didn't seem to be real. He called it magic. If he were to be honest with the people he would take away the magic. For example, he would lay a pencil on a table and make it move with his mind. In reality he blew on the pencil to make it move. There was a misdirection involved where he appeared to be focusing really hard and thus causing he audience to focus on the pencil as well. While they started at the pencil his lips were free to pucker up and blow.
The tone of certainty is one such misdirection. While you sit and listen to the biotech leaders you get the sense of a pending success story. The same tone was in effect 11 years ago but we know something was amiss. People lost a great amount of money. However, had they listened closely 11 years ago, and this year as well, they would have heard the real story. The people speaking were speaking about making a company money, without making a product. They spoke of making partnerships. They spoke of being acquired. They did not speak of the tricks they intend to use to get the money. Making a product takes too long and costs too much. Seattle folk don't have the time, money nor expertise to do what is needed. They are selling something else. The question, is it real or is it bullshit?
The best way to sum up the concept of certainty, bullshit, and biotechnology is to take on the case of Sam Waksal. He wasn't an honest man. He didn't invent or discover Erbitux. He ran a biotech business. He got rich and went to jail long before Erbitux made its first sale. People lost money but Sammy made sure he and his friends and family weren't in that group. A few of them did some time and that is very sad. But what remains is Sams influence on the business. Sam does talk pretty and you have to when there is a book on your shameful career, yet you go on to found another biotech company.
How many speakers on the Innovation Northwest stage would shun the likes of Waksal. He speaks as they do. He knows the industry. People give him millions of dollars in spite of his history. Perhaps it is all about being a good magician. Get people writing checks and keep them from looking at the past. It's not a Cargo Cult, it's a shiny new biotech company and the future is looking bright. Trust us.
Imagine if you will, the very first Innovation Northwest meeting 11 years ago. The individuals speaking at those meetings were all leaders of the field. They spoke of how to pursue an IPO, how to get initial funding, and all of the money ideas of the time. This years meeting was no different, only the ways of getting money have changed. It is much more difficult to get money because whatever they were talking about 11 years ago didn't go very well. One thing that the CCS takes great interest is in the ways people talk about things that aren't so. The tones of certainty that were used 11 years ago were probably the same as those used this year. It is a tone of certainty that makes you believe that what you are hearing is about progress. But is it?
James Randi spent his early career as a magician, tricking people into believing things that didn't seem to be real. He called it magic. If he were to be honest with the people he would take away the magic. For example, he would lay a pencil on a table and make it move with his mind. In reality he blew on the pencil to make it move. There was a misdirection involved where he appeared to be focusing really hard and thus causing he audience to focus on the pencil as well. While they started at the pencil his lips were free to pucker up and blow.
The tone of certainty is one such misdirection. While you sit and listen to the biotech leaders you get the sense of a pending success story. The same tone was in effect 11 years ago but we know something was amiss. People lost a great amount of money. However, had they listened closely 11 years ago, and this year as well, they would have heard the real story. The people speaking were speaking about making a company money, without making a product. They spoke of making partnerships. They spoke of being acquired. They did not speak of the tricks they intend to use to get the money. Making a product takes too long and costs too much. Seattle folk don't have the time, money nor expertise to do what is needed. They are selling something else. The question, is it real or is it bullshit?
The best way to sum up the concept of certainty, bullshit, and biotechnology is to take on the case of Sam Waksal. He wasn't an honest man. He didn't invent or discover Erbitux. He ran a biotech business. He got rich and went to jail long before Erbitux made its first sale. People lost money but Sammy made sure he and his friends and family weren't in that group. A few of them did some time and that is very sad. But what remains is Sams influence on the business. Sam does talk pretty and you have to when there is a book on your shameful career, yet you go on to found another biotech company.
How many speakers on the Innovation Northwest stage would shun the likes of Waksal. He speaks as they do. He knows the industry. People give him millions of dollars in spite of his history. Perhaps it is all about being a good magician. Get people writing checks and keep them from looking at the past. It's not a Cargo Cult, it's a shiny new biotech company and the future is looking bright. Trust us.
An Old Idea
The company is called NeuroPhage. The idea is one that I have personally worked on at several different companies. Bind something to amyloid beta (antibody, phage, peptide) and amyloid plaques will not form. The population of potential customers and their end of life spiral makes this disease indication enormously popular among biotechnology companies. You might call this one the holy grail of biotech.
The concept makes several assumptions. It is assumed that binding to amyloid beta in the laboratory will scale to binding amyloid beta inside the human brain. Scaling from a cell line in a petri dish, to an animal model, to a human being, is not something that bio-scientists can rely on.
It is assumed that preventing the formation of amyloid plaques will result a significant reduction in the symptoms of Alzheimers Disease.
It is assumed that phage will be more efficacious than using antibodies or small molecule approaches.
Having done this research I take great interest in the amyloid beta story. I watched others attempt to cure or treat this disease in Cargo Cult amazement. At the highest levels the amount of thought that seemed to go into the "research" was to hire people to find the binder. The executive view (and their investors) was to name the molecule and send in the lower ranking people to finish up the details... of curing Alzheimer's!
On NeuroPhages' website they offer up some evidence. They begin with the perfect world graphic arts version of the disease and how the drug will work. They then show two pictures. In one you see the plaques in a "vehicle control", which appears to be a brain slice. In the other picture there appears to be far less plaques. That is the drug working.
This is a red flag. Science is not done by selective photography. I've seen this trick used in many fields, especially RNAi. You show a knock-down by simply finding the highs and lows of a non-homogeneous system. In this case the system is a brain slice. As far as we know the pictures offered up could be from the same brain slice. We are left to trust the authors that they are not interested in pulling the wool over our eyes.
We're off to a bad start. Now comes the worst part. How do they propose the drug get into a humans brain? How do you measure phage floating around in a brain, breaking up plaques. The Alzheimer's patient is not officially diagnosed with the disease until after an autopsy. Where is the graphic art depiction of drug administration and finding of the target? There is an entire field of science that is not being addressed by the Cargo Cult here. It's called ADME. Tracking the phage on its journey into the body, to the plaques, breaking up the plaques and being cleared is not something that can be done. That frees up management to worry about other things like financing and perhaps adding information to one of the sparsest websites in the biz.
It won't work. I've seen it not work over and over. It's an idea that is taken to the point of, "what do we do next?" and left off to lower paid worker bees. In real science, this is the starting point. Did this really work? How did it work? Does it work every time? Will it work in a human being? The questions are instead left up to the white lab coat people who have only one option in reporting their findings, tell management it works and don't bother with the details that weren't ask for. Keep the story just as it is on the website. There is no turning back now. Look to the skies and wait for the delivery of the Cargo Airplane that carries the cure for Alzheimer's. Once it lands get your sales people together and get ready to make some money.
The concept makes several assumptions. It is assumed that binding to amyloid beta in the laboratory will scale to binding amyloid beta inside the human brain. Scaling from a cell line in a petri dish, to an animal model, to a human being, is not something that bio-scientists can rely on.
It is assumed that preventing the formation of amyloid plaques will result a significant reduction in the symptoms of Alzheimers Disease.
It is assumed that phage will be more efficacious than using antibodies or small molecule approaches.
Having done this research I take great interest in the amyloid beta story. I watched others attempt to cure or treat this disease in Cargo Cult amazement. At the highest levels the amount of thought that seemed to go into the "research" was to hire people to find the binder. The executive view (and their investors) was to name the molecule and send in the lower ranking people to finish up the details... of curing Alzheimer's!
On NeuroPhages' website they offer up some evidence. They begin with the perfect world graphic arts version of the disease and how the drug will work. They then show two pictures. In one you see the plaques in a "vehicle control", which appears to be a brain slice. In the other picture there appears to be far less plaques. That is the drug working.
This is a red flag. Science is not done by selective photography. I've seen this trick used in many fields, especially RNAi. You show a knock-down by simply finding the highs and lows of a non-homogeneous system. In this case the system is a brain slice. As far as we know the pictures offered up could be from the same brain slice. We are left to trust the authors that they are not interested in pulling the wool over our eyes.
We're off to a bad start. Now comes the worst part. How do they propose the drug get into a humans brain? How do you measure phage floating around in a brain, breaking up plaques. The Alzheimer's patient is not officially diagnosed with the disease until after an autopsy. Where is the graphic art depiction of drug administration and finding of the target? There is an entire field of science that is not being addressed by the Cargo Cult here. It's called ADME. Tracking the phage on its journey into the body, to the plaques, breaking up the plaques and being cleared is not something that can be done. That frees up management to worry about other things like financing and perhaps adding information to one of the sparsest websites in the biz.
It won't work. I've seen it not work over and over. It's an idea that is taken to the point of, "what do we do next?" and left off to lower paid worker bees. In real science, this is the starting point. Did this really work? How did it work? Does it work every time? Will it work in a human being? The questions are instead left up to the white lab coat people who have only one option in reporting their findings, tell management it works and don't bother with the details that weren't ask for. Keep the story just as it is on the website. There is no turning back now. Look to the skies and wait for the delivery of the Cargo Airplane that carries the cure for Alzheimer's. Once it lands get your sales people together and get ready to make some money.
Saturday, March 05, 2011
Delivering RNAi
I would be remiss if I were to not revisit the Cargo Cult of RNAi.
Last week we had a conference on the Cargo Cults of Seattle. RNAi was represented by PhaseRx. Since their inception they have had very little to report besides their 19 million dollar series A financing. They do however make very bold claims on their website.
How do they have evidence of efficacy for the diseases if they've been held in check by delivery. Does their delivery include a ride straight to the cells of interest, avoiding a depletion of drug by being absorbed by other cells?
The problem is scalability. If you work as an engineer in a biopharmaceutical manufacturing facility you start small and scale up. There are certain relationships involved in scaling up that have been addressed by the industry, resulting in predictable outcomes. But with RNAi, they have predicted the outcomes without doing the research. The outcomes exist mostly on company websites. What do they now know that makes everything work where it failed in the past? As predicted by the CCS, the RNAi industry is not evolving.
Last week we had a conference on the Cargo Cults of Seattle. RNAi was represented by PhaseRx. Since their inception they have had very little to report besides their 19 million dollar series A financing. They do however make very bold claims on their website.
RNAi therapeutics, also referred to as short interfering RNA or siRNA, have demonstrated broad applicability to many therapeutic areas, including cancer, inflammatory and autoimmune diseases, infectious disease and metabolic disorders.
These promising therapeutics are being held largely in check today by the lack of broadly applicable delivery technology. RNAi therapeutics generally cannot, on their own, penetrate the cell membrane and gain access to the cytoplasm where they can reach the drug targets.
The PhaseRx polymer system overcomes the central stumbling block in the field of RNAi therapeutics by delivering RNAi molecules into the cytoplasm where they can reach and inhibit the desired target of interest.
How do they have evidence of efficacy for the diseases if they've been held in check by delivery. Does their delivery include a ride straight to the cells of interest, avoiding a depletion of drug by being absorbed by other cells?
The problem is scalability. If you work as an engineer in a biopharmaceutical manufacturing facility you start small and scale up. There are certain relationships involved in scaling up that have been addressed by the industry, resulting in predictable outcomes. But with RNAi, they have predicted the outcomes without doing the research. The outcomes exist mostly on company websites. What do they now know that makes everything work where it failed in the past? As predicted by the CCS, the RNAi industry is not evolving.
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