There is a technique that is used in biotechnology known as phage display. In this technology a virus that attacks bacteria is used to display a short peptide. Without boring the reader with the details, this is a technique known as evolution in an instant. What you do is subject a library of peptide displaying phage to a protein target. You wash away non-binding phage, amplify binding phage and repeat. What you hope to end up with are peptides that bind to a target. You are repeating because it takes a while to get rid of non-binding phage. They must be slowly selected against in an evolution like process.
During the selection process many other things can happen. Contamination of the library of phage can happen. Most interesting however is the selection of phage that are in the original library. These phage will predominate after a while because they grow faster than the other phage. At least that is the theory. A company called New England Biolabs sells the phage libraries. Each lot appears to have a set of contaminants that will come out after a period of selection. They do not seem to appear because they bind to a protein target. They lack a gene that the rest of the library has. This gene causes the phage plaques (formed on bacterial lawns) to turn blue. The contaminating phage form white plaques. Perhaps this is part of the selection of the phage since the normal state of the DNA lacks the blue plaque gene.
One such phage that has been seen displays the peptide GETRAPL. That is code for 7 amino acids, glycine-glutamic acid-threonine-arginine-alanine-proline-leucine. A co-worker of mine found this sequence. I recognized it and ran it in our database. Sure enough, it showed up several times. There was not particular protein linked to it however. It was linked to later stages of selection however. We noted that the plaques were white in all cases. We typed it into Google and found an interesting group of papers.
Researchers at a different laboratories had found this sequence while using phage display against their targets. The first paper "Design and Assay of Inhibitors of HIV-1 Vpr Cell Killing and Growth Arrest Activity Using Microbial Assay Systems". The next, "Development of efficient viral vectors selective for vascular smooth muscle cells". Completely unrelated, yet they used the peptide to validate their work. They published and ...?
In physics you set up a system. In that system many things are happening. Pressure changes, concentration of molecules changes, heat is given off and so on. One of the question you can ask about a system is whether or not work has been done at a certain period of time. For example, you load a box onto a conveyor belt that takes the box and drops it onto another conveyor belt that puts the box back you to load onto the first conveyor belt. You are sweating. Boxes are moving but only in a circle. Work is not really getting done.
The GETRAPL story is like that. Did work get done? Did anything scientific get done? The papers on GETRAPL appear to have ended. No one is talking about the peptide but there was a time when this little contaminant from a phage display library made two labs get out their typewriters and type of the story of how they got the peptide and what they did with it. And it did something! The circle here is starting with the library, getting the same sequence, publishing and moving on to something else. The way to stop the non-working cycle is to publish a paper on the sequence and let people know when they are being misled. The system here is science as it is being practiced by PhD scientists and journal editors. The people who sell the libraries can also stop the non-work cycle. The system is not producing work.
Feynman said that he hoped we learned something during our educations. Something you can't teach. You can easily learn how a phage library is made and used. You can learn some computer software that will help you assess the peptides you end up with. Finding a protein binding peptide is a rare event, but that is not what is taught. To me, that is the interesting thing about the technique. It is just one of many techniques that can be used to study a protein and it's interactions. You can learn all about the protein prior to using phage display. You can get up a give a talk to the Academy of Sciences on the details of your work. But in the end you have to look at your results. You have to use something inside of you that is not taught. Critical thinking perhaps. Can it really be binding to the target? How can I prove that? How can I disprove that? How can I be sure of any result?
One way of looking at GETRAPL is very obvious to laboratory people. You look at the DNA sequences of each phage that displays GETRAPL. Are they identical or are there various sequences using different codons that code for GETRAPL. This would be strong evidence that it is not being selected for because the original phage grows faster than the rest of the library. Another modern day trick that we applied was to Google the sequence and see if anyone could back up your hopes and dreams that it binds to a specific target. Your education can teach you about the tools. It is up to you to use them.
There are many phage like GETRAPL. There is a paper published by one of the leading phage display scientists that discusses their existance. What is selecting these phage is still unknown. Developing an explanation and proving it is science. There are scientists who currently work on software that can take a list of sequences that come out of a phage display selection process and help you understand what you've got. If you sequence 100 phage and they are all the same sequence for example, the computer only sees one sequence. The computer is weeding out repeated sequences because it indicates selection based on non-binding factors such as faster growing phage. The computer software continues to add new features to help you find binding phage. Someday you could simply put files into this software and it will give you a list of possible binding targets. It could search your own database as well those on the internet or in Pubmed. This is still not going to tell you the whole story. You have to develop an assay. They teach you about assays. The assays however, give you another set of data that you have to interpret. This is what Feynman was hoping you would know how to do. Think scientifically. Ignore your hopes and dreams of getting published and moving on to more interesting projects. Don't act on your desire to take that peptide and fuse it into some elaborate molecule you designed and toss that into an elaborate assay and prove that you can cure AIDS! Slow down. Is the data really saying what you think it is. Think critically and proceed logically.
There are many other peptides that have been discovered that are mere contaminants. The claims that their finders have made on their behalf are quite fancy. Big science words were used and put together in a way that is certainly feasible. No work was done however. Just words used to describe a set of letters that represent amino acids. What is really going on can open doors. What is really going on can make the planes land! But they fade away, these research projects. No resolution. No work was done. No planes landed.
Friday, June 30, 2006
Wednesday, June 28, 2006
Ben Franklin
I watched an old documentary on Ben Franklin last night. As a young man he owned and operated print shops and newspapers and made a lot of money at it. He was editor, writer, and printer. Currently, newspaper editors go to meetings and review union dispute contracts and so on. The point is that people did not have as much information to deal with back then. Ben Franklin could do all of the above jobs because each one was managable. As populations grow and industries grow more details get spread out to the point that no one really knows the whole story.
After Franklin turned 42 he decided to quit running his businesses and focus his time on science. This was during a time when most scientists were men of liesure. They were amatuers who were amusing themselves by observing nature and trying to discover something no one had yet discovered. Franklins field was electricity. Like other amatuer scientists he had to make much of his own equipment. He relied upon his understanding of electricity to create electrodes and electron generators. He ended up getting famous from harnessing this energy and telling about it in a manner far different than the way scientists talk today. He gave us the lightning rod which is still in use today, unchanged from Franklins time.
Scientists today are paid to do science. Most of the profit generated from science comes from selling scientists equipment and kits. I have sat in meetings where a scientist will describe how he developed an assay. Step one, purchase assay. Step two, change a few buffers. Step three, use charts and graphs to describe the postive effects of the changes. Controls optional.
In Ben Franklins time it appeared that the scientists were the ones in the lab observing and doing experiements. They did not have to keep notebooks if they didn't want to. They occasionally caused themselves harm such as when Ben shocked himself unconcious accidentally while revving up enough volts to try and kill a turkey. Some scientists were extremely diligent when it came to measurements. Some were more qualitative when studying completely unknown phenomena. They all worked because so much was unknown and knowledge was ripe for the picking. Who wouldn't want to wake up, dream up ways of testing ideas and watch the results happen first hand? For this Ben Franklin gave up running his business and spent ten years pursuing. The end results were very successful and rewarding.
Back to biotechnology, the cargo cult science industry. You've got 100 billion dollars and PhDs from the finest universities. You've also got the research from the universities flowing out with zero resistance from the schools. There is money and there are the nations best educated people working every day to contribute to scientific progress. Where are the results?
In this Benjamin Franklin documentary there were dramatizations of Ben and his comrades standing around the lab watching experiments from start to finish. There was a parlor game that they performed where everyone would hold hands in a circle. At one end of the circle someone held the cathode. At the other, someone would touch the anode and everyone in the circle would get a cute little shock all at the same time. Watching everyone jump at the same time, some hair sticking up, was of great entertainment value in those days. People wanted to see the results first hand.
These days we have computers. We have computer software that sets up graphs, runs statistical analysis and so on. Meetings are always held in board rooms. Never, even in small companies, do PhD scientists hold meetings in laboratories where the work is done. No one goes to the laboratory bench to watch any part of an experiment. In the board room, computer screen up on the wall thanks to the latest technology from Microsoft, graphs are shown, one after the other. They are meant to explain the binding powers of antibodies or the knock-down effect of siRNA. They show the "score" of an arthritic set of mice, with and without the next big anti-arthritus drug.
In my previous job there were several boxes of dead mice sitting in jars of formaldehyde, waiting to be "scored" for their degrees of arthritus. The problem was that you didn't need to be a great scientist to tell that nothing had happened. The work would have taking weeks and very little would have came of it. Worst of all you would have the charts and graphs to prove it, blasted up on that board room wall where the scientists would look on with disapproval of these uninteresting results. They didn't want to watch the mice get the injections. They didn't want to monitor the disease progression. They didn't want to help score the mice. They wanted the results, up on the board with bar graphs. Arthritus was measured by the height of a bar on a graph sitting next to another bar that represents the drug affect. A smaller bar meant less arthritus.
They never did get the siRNA cure for arthritus. As in most science project they slowly let it fade away, hoping that no one noticed. As a corporation they do not have to tell the scientific community anything about their work. Failure is described to non-scientific investors and par for the course. Got to keep the pipeline diversitified, just like a stock portfolia. Some things just don't work. You understand. And slowly billions and billions of dollars disappear. It's not an easy living, but it beats getting in that lab and testing your ideas in front of others. That type of work requires real scientists who want to see what is happening. Like Ben.
After Franklin turned 42 he decided to quit running his businesses and focus his time on science. This was during a time when most scientists were men of liesure. They were amatuers who were amusing themselves by observing nature and trying to discover something no one had yet discovered. Franklins field was electricity. Like other amatuer scientists he had to make much of his own equipment. He relied upon his understanding of electricity to create electrodes and electron generators. He ended up getting famous from harnessing this energy and telling about it in a manner far different than the way scientists talk today. He gave us the lightning rod which is still in use today, unchanged from Franklins time.
Scientists today are paid to do science. Most of the profit generated from science comes from selling scientists equipment and kits. I have sat in meetings where a scientist will describe how he developed an assay. Step one, purchase assay. Step two, change a few buffers. Step three, use charts and graphs to describe the postive effects of the changes. Controls optional.
In Ben Franklins time it appeared that the scientists were the ones in the lab observing and doing experiements. They did not have to keep notebooks if they didn't want to. They occasionally caused themselves harm such as when Ben shocked himself unconcious accidentally while revving up enough volts to try and kill a turkey. Some scientists were extremely diligent when it came to measurements. Some were more qualitative when studying completely unknown phenomena. They all worked because so much was unknown and knowledge was ripe for the picking. Who wouldn't want to wake up, dream up ways of testing ideas and watch the results happen first hand? For this Ben Franklin gave up running his business and spent ten years pursuing. The end results were very successful and rewarding.
Back to biotechnology, the cargo cult science industry. You've got 100 billion dollars and PhDs from the finest universities. You've also got the research from the universities flowing out with zero resistance from the schools. There is money and there are the nations best educated people working every day to contribute to scientific progress. Where are the results?
In this Benjamin Franklin documentary there were dramatizations of Ben and his comrades standing around the lab watching experiments from start to finish. There was a parlor game that they performed where everyone would hold hands in a circle. At one end of the circle someone held the cathode. At the other, someone would touch the anode and everyone in the circle would get a cute little shock all at the same time. Watching everyone jump at the same time, some hair sticking up, was of great entertainment value in those days. People wanted to see the results first hand.
These days we have computers. We have computer software that sets up graphs, runs statistical analysis and so on. Meetings are always held in board rooms. Never, even in small companies, do PhD scientists hold meetings in laboratories where the work is done. No one goes to the laboratory bench to watch any part of an experiment. In the board room, computer screen up on the wall thanks to the latest technology from Microsoft, graphs are shown, one after the other. They are meant to explain the binding powers of antibodies or the knock-down effect of siRNA. They show the "score" of an arthritic set of mice, with and without the next big anti-arthritus drug.
In my previous job there were several boxes of dead mice sitting in jars of formaldehyde, waiting to be "scored" for their degrees of arthritus. The problem was that you didn't need to be a great scientist to tell that nothing had happened. The work would have taking weeks and very little would have came of it. Worst of all you would have the charts and graphs to prove it, blasted up on that board room wall where the scientists would look on with disapproval of these uninteresting results. They didn't want to watch the mice get the injections. They didn't want to monitor the disease progression. They didn't want to help score the mice. They wanted the results, up on the board with bar graphs. Arthritus was measured by the height of a bar on a graph sitting next to another bar that represents the drug affect. A smaller bar meant less arthritus.
They never did get the siRNA cure for arthritus. As in most science project they slowly let it fade away, hoping that no one noticed. As a corporation they do not have to tell the scientific community anything about their work. Failure is described to non-scientific investors and par for the course. Got to keep the pipeline diversitified, just like a stock portfolia. Some things just don't work. You understand. And slowly billions and billions of dollars disappear. It's not an easy living, but it beats getting in that lab and testing your ideas in front of others. That type of work requires real scientists who want to see what is happening. Like Ben.
Thursday, June 22, 2006
Education
A story in the paper yesterday asked the question, is a college education still a good investment? On one hand, a college education is an experience that young people can have. You live on your own, with thousands of other kids. You go to classes and learn about things that you will be asked about on a test. On the other hand it's a very expensive four years of your life. You will have little time to earn money. At the same time the spending of money will be accelerated. You are hoping that later in life your earning potential will be accelerated. If your parents can help you are ahead of the game. If you are putting yourself through college this is a major risk of an investment. What guarentees are there that you will have a good job some day?
People like to bring up the fact that Bill Gates never finished college and now he's the riches guy in the world. The link to education and money however is pretty solid. One of the main reasons is that all higher paying jobs require a degree just to get your foot in the door. If you're like some people you have contacts through family members are other associations who can give you that little extra something that gets you the job. If not you are forced to pay your dues. Get the education and then get the rest of the package that will land you your high paying job. Bill Gates had the rest of the package to begin with.
What is the rest of the package? I have a degree in Biochemistry. During the course of my education I used a Mass Spectrometry machine to analyze the compounds that I produced in organic chemistry lab. When a potential employer wants someone with these skills however, I cannot use my education. They are looking for hands on experience. What they are saying is that my education was superficial. They want something real because you won't be taking tests on Mass Spec on the job. You will be using the machine for what is was intended. Education is thus a mere introduction to the world you might be working in. As time marches on during this rapid advancement in technology, is education keeping pace with it's Bachelors, Masters, and Doctorol programs?
Vocational schools teach people how to perform such jobs as mechanic, plumber and so on. Plumbing has remained the same for a long time. Cars have become a little more advanced. In most new cars you have to take your car back to the dealer where specialized mechanics can run computer diagnostics. They have specialized tools fit to particular models. I'm no expert but I am guessing that individuals with basic mechanic degrees from vocational schools have additional training required if they are to work in a dealers garage.
Feynman talked about educators assuming that what they were teaching was actually learned. In math you can teach a student that 2 plus 2 equals 4. In the real world, does the student understand that 2 apples and 2 oranges equal 4 pieces of fruit and not 4 apples? I see hiring managers these days requiring education and experience.
For example, take this description for a researcher position:
People like to bring up the fact that Bill Gates never finished college and now he's the riches guy in the world. The link to education and money however is pretty solid. One of the main reasons is that all higher paying jobs require a degree just to get your foot in the door. If you're like some people you have contacts through family members are other associations who can give you that little extra something that gets you the job. If not you are forced to pay your dues. Get the education and then get the rest of the package that will land you your high paying job. Bill Gates had the rest of the package to begin with.
What is the rest of the package? I have a degree in Biochemistry. During the course of my education I used a Mass Spectrometry machine to analyze the compounds that I produced in organic chemistry lab. When a potential employer wants someone with these skills however, I cannot use my education. They are looking for hands on experience. What they are saying is that my education was superficial. They want something real because you won't be taking tests on Mass Spec on the job. You will be using the machine for what is was intended. Education is thus a mere introduction to the world you might be working in. As time marches on during this rapid advancement in technology, is education keeping pace with it's Bachelors, Masters, and Doctorol programs?
Vocational schools teach people how to perform such jobs as mechanic, plumber and so on. Plumbing has remained the same for a long time. Cars have become a little more advanced. In most new cars you have to take your car back to the dealer where specialized mechanics can run computer diagnostics. They have specialized tools fit to particular models. I'm no expert but I am guessing that individuals with basic mechanic degrees from vocational schools have additional training required if they are to work in a dealers garage.
Feynman talked about educators assuming that what they were teaching was actually learned. In math you can teach a student that 2 plus 2 equals 4. In the real world, does the student understand that 2 apples and 2 oranges equal 4 pieces of fruit and not 4 apples? I see hiring managers these days requiring education and experience.
For example, take this description for a researcher position:
Bachelor’s degree in a scientific discipline.
Minimum 2 years laboratory experience in molecular and/or cell biology.
Demonstrated working knowledge of scientific principles and standard laboratory practices.
Familiarity with Virology and/or Immunology.
Knowledge and experience in the correct handling of hazardous and radioactive substances.
Does familiarity with virology and/or immunology mean that these two fields are almost the same? Does the scientific degree mean that you can have a degree in physics? There is more to this job description:
Perform general molecular biology techniques, including PCR, cDNA cloning, RT PCR, RNAi, expression cloning, and cDNA mutagenesis.
Perform cell culture and FACs analysis.
Assist in sample preparation for Mass Spec. analysis.
Assist in design and development of in vitro assays.
That's a lot of stuff to know in two years. All of these skills are taught in 4 year degrees but not in a four year physics degree. There are no degrees that train hiring managers to write up job descriptions. Human resource people are generally considered to be the experts here but this is not a science. It is an attempt to hire the right person for a a job. You could just say you are looking for someone with a degree in Biochemistry who can do some molecular biology work. RNAi? The field is too new to have any meaning. FACs? Just a machine that is complicated but not beyond the learning curve for a college grad. Development of assays? It's more of an art that people know or do not. I don't think it can be taught. Kits can be sold but developing an assay is real science. If we had an assay for cancer for example we would understand cancer much better.
The real issue of education and employment is the same as a Cargo Cult ceremony and airplanes landing. If you are in charge of hiring, do you know the difference between a typist and a secretary? If you are seeking employment do you know that having the skills and education is what you need to get an interview? Doing well at the interview gets you the job. The additional skills are what make the airplanes land. Many human endeavors fail because someone started with a lack of knowledge or finished with a lack of knowledge. True knowledge is what education should lead to. A college degree is a weak substitution for evidence of true knowledge.
Monday, June 12, 2006
Assays and Reality
When you work in a laboratory in the biomedical world you have to learn a few assays. An assay is a qualitative or quantitative analysis of a substance to determine its components. You put on your white lab coat, grab your pipettes and go do an assay. Are you doing science?
The cargo cult theory says that people will follow the form what they see others do in hopes of acheiving the same results. Scientists run assays so if you want to be a successful scientist someone had better get in that lab and run some assays. Let's say you are an office scientist and you do research on HIV. You will have to hire someone to work in the lab who knows how to test for the HIV virus. There will be an HIV assay. The fastest assay involves testing for antibodies against HIV. This is often the case for assays. You don't test for the component directly but for things associated with the component. The further you get away from the lab however, the less you know about the details of the assay.
The office scientist usually knows about the assay. An ELISA assay involves using an antibody against a protein. The antibody has an enzyme physically linked to it. The enzyme is tested for by adding a substrate that will create a color when cleaved by the enzyme. Remember you are really interested in the protein that is bound by the antibody that is linked to the enzyme that causes the substrate to make the color. How do you assess the significance of the simple development of a color?
The ELISA assay was developed long ago. Someone else did the work to determine that this assay could be used as an assay. Those who come along and choose to use it must determine of the things they are testing for can be used in a similar manner. Here is the cargo cult moment. An office scientist could instruct the young lab worker to run an ELISA assay to determine of protein X is present in some sample. The young lab worker buys a kit, runs the assay and looks for the presence of a color. This is similar to setting up an airport and looking to the skies for airplanes.
You have a sample that you suspect contains your protein. You want to know if it is there and how much of it is there. If you accidentally use too much antibody you will get a strong color. If you use too little you will get a weak color where a strong color should have been observed. You must have controls. If you want to know how much you must have a standard curve. The standard curve must involve y = mx + b and linear regression if it is to be understood quantitatively. Your standard curve must be prepared in the same medium as your sample. Your color must be read at the proper wavelenght. All samples must be stopped at the same time with the acid. If you were to seriously teach about the ELISA there would be more time spent on these issues than on any discussion involving antibodies and substrates. Light absorbance readings for example, have limitations. There is a linear range for reading the absorbance of a color in the machines used in the lab. That means there are limitations that must be known and accounted for. The standard curve is also a test of the limitations.
I bring all of this up because of the limitations of measurements in any science. The machine that measures the abosorbance of a colored solution has limitations. The ELISA assay has an upper and lower limit of detection no matter what you are measuring. That means there is a range where useful and accurate information can be obtained. Do you know what your range is?
Beyond ELISAs there are many assays used in basic biomedical research. They all have limitations that are woven together in a way that can cause great confusion. Even if you have 100% pure samples you will have a margin of error in your assay measurements. Imagine then trying to measure the amount of a protein in a blood sample or in kidney cells. Can you find an internal standard in blood? Are proteins sometimes upregulated and downregulated in times and concentrations that are out of our range to measure? I say hell yes they are yet we constantly read about people claiming to have accurately made the measurements nonetheless. Their measurements conveniently support their assumptions underlying the purpose of the research.
I once worked with RAW cells which are precursors to Osteoclasts. If you add RANK ligand to a RAW cell culture they will fuse together and form large multinucleated osteoclasts in about five days. I observed this process many times. I tested for the presence of tartrate resistant alkaline phosphatase (TRAP) every day. I could see TRAP on the surface of the Raw cells just after adding the RANK ligand. As the cells began to fuse I could see the TRAP on one side of the new ball of cells. By the fourth day the TRAP was nearly gone and the osteoclasts were predominant. These were simple observations. If I wanted to know more about TRAP and it's role in osteoclastogenisis I would have to get more clever than cell staining and microscopic observation. That's when I leave the cargo cult world and figure out what to do. I still have the lab coat and the microscope but I have to do something scientific. I have to know my limitations. I have to think about the location of the TRAP and how the cells pH or polarity might be affecting that location. How might the cells pH or polarity affect my measurements? In the end I would not propose any reasons for the TRAP regulation. I would merely describe what I think is going on. That's all. Next I would follow a lead that came up during the TRAP research. The goal would not be to cure osteoporosis. It's simply to observe nature.
It's like a reality show that only a few can watch. Do you get that channel? If so do you turn it on? If so is the picture fuzzy or clear? If it's clear do you have the ability to tell others about it? If so are you telling the right peope about it?
The cargo cult theory says that people will follow the form what they see others do in hopes of acheiving the same results. Scientists run assays so if you want to be a successful scientist someone had better get in that lab and run some assays. Let's say you are an office scientist and you do research on HIV. You will have to hire someone to work in the lab who knows how to test for the HIV virus. There will be an HIV assay. The fastest assay involves testing for antibodies against HIV. This is often the case for assays. You don't test for the component directly but for things associated with the component. The further you get away from the lab however, the less you know about the details of the assay.
The office scientist usually knows about the assay. An ELISA assay involves using an antibody against a protein. The antibody has an enzyme physically linked to it. The enzyme is tested for by adding a substrate that will create a color when cleaved by the enzyme. Remember you are really interested in the protein that is bound by the antibody that is linked to the enzyme that causes the substrate to make the color. How do you assess the significance of the simple development of a color?
The ELISA assay was developed long ago. Someone else did the work to determine that this assay could be used as an assay. Those who come along and choose to use it must determine of the things they are testing for can be used in a similar manner. Here is the cargo cult moment. An office scientist could instruct the young lab worker to run an ELISA assay to determine of protein X is present in some sample. The young lab worker buys a kit, runs the assay and looks for the presence of a color. This is similar to setting up an airport and looking to the skies for airplanes.
You have a sample that you suspect contains your protein. You want to know if it is there and how much of it is there. If you accidentally use too much antibody you will get a strong color. If you use too little you will get a weak color where a strong color should have been observed. You must have controls. If you want to know how much you must have a standard curve. The standard curve must involve y = mx + b and linear regression if it is to be understood quantitatively. Your standard curve must be prepared in the same medium as your sample. Your color must be read at the proper wavelenght. All samples must be stopped at the same time with the acid. If you were to seriously teach about the ELISA there would be more time spent on these issues than on any discussion involving antibodies and substrates. Light absorbance readings for example, have limitations. There is a linear range for reading the absorbance of a color in the machines used in the lab. That means there are limitations that must be known and accounted for. The standard curve is also a test of the limitations.
I bring all of this up because of the limitations of measurements in any science. The machine that measures the abosorbance of a colored solution has limitations. The ELISA assay has an upper and lower limit of detection no matter what you are measuring. That means there is a range where useful and accurate information can be obtained. Do you know what your range is?
Beyond ELISAs there are many assays used in basic biomedical research. They all have limitations that are woven together in a way that can cause great confusion. Even if you have 100% pure samples you will have a margin of error in your assay measurements. Imagine then trying to measure the amount of a protein in a blood sample or in kidney cells. Can you find an internal standard in blood? Are proteins sometimes upregulated and downregulated in times and concentrations that are out of our range to measure? I say hell yes they are yet we constantly read about people claiming to have accurately made the measurements nonetheless. Their measurements conveniently support their assumptions underlying the purpose of the research.
I once worked with RAW cells which are precursors to Osteoclasts. If you add RANK ligand to a RAW cell culture they will fuse together and form large multinucleated osteoclasts in about five days. I observed this process many times. I tested for the presence of tartrate resistant alkaline phosphatase (TRAP) every day. I could see TRAP on the surface of the Raw cells just after adding the RANK ligand. As the cells began to fuse I could see the TRAP on one side of the new ball of cells. By the fourth day the TRAP was nearly gone and the osteoclasts were predominant. These were simple observations. If I wanted to know more about TRAP and it's role in osteoclastogenisis I would have to get more clever than cell staining and microscopic observation. That's when I leave the cargo cult world and figure out what to do. I still have the lab coat and the microscope but I have to do something scientific. I have to know my limitations. I have to think about the location of the TRAP and how the cells pH or polarity might be affecting that location. How might the cells pH or polarity affect my measurements? In the end I would not propose any reasons for the TRAP regulation. I would merely describe what I think is going on. That's all. Next I would follow a lead that came up during the TRAP research. The goal would not be to cure osteoporosis. It's simply to observe nature.
It's like a reality show that only a few can watch. Do you get that channel? If so do you turn it on? If so is the picture fuzzy or clear? If it's clear do you have the ability to tell others about it? If so are you telling the right peope about it?
Friday, June 09, 2006
siRNA Pathology
The Cargo Cult Airport has leaders. They send the people out with coconuts over their ears. They make sure the fires are lit along the side of the runway. If it's anything like the American corporate style of leadership, it is assumed that the leaders know more about why these things are done. The followers just follow. Leaders instruct because they are "in the know".
siRNA has been in existance a relatively short period of time. As soon as it began however, scientist began positioning themselves into the leadership role. There were rules set up for how to design siRNA. There were papers written on the best way to get the most out of your siRNA knock-out. Like a Cargo Cult Airport however, it wasn't known how siRNA really worked. The experts seemed have a disdain for research that involved a mechanism of action. One of "the rules" for example was that the siRNA had to consist of a certain percentage gaunisine and cytosine. What was the data used to come to that conclusion? Five siRNA KOs? Ten? Were they in mice or hamsters?
Eventually the scientists have to come up with a MOA, mechanism of action. It has been decided that the mechanism of action involves mRNA interacting with an enzyme called Dicer. One of the leading siRNA researchers, Dr. Kazunari Taira of the University of Tokyo describes it this way:
The mechanism responsible for dsRNA-induced gene silencing, which proceeds via a two-step mechanism, appears to have been strongly conserved during evolution. In the first step, long dsRNAs are recognized by a nuclease in the RNase III family known as Dicer, which cleaves the dsRNA into small interfering RNAs (siRNAs) of 21–23 nt. These siRNAs are incorporated into a multicomponent nuclease complex, known as RISC, that is then responsible for the destruction of cognate mRNAs.
Dr. Taira was a leader in siRNA research. More specifically he was ranked number 4 (most cited authors) out of the 25,000 researchers who have published papers on siRNA. He took on the toughest piece of the puzzle, the MOA and he got burned. A panel at the university where he worked said that he "likely fabricated papers on a potential medical breakthrough". As I've stated before, big time scientists do not work in laboratories. They work in offices. They communicate on the things that take place in labs but they rarely go inside their labs. One of the people who did work in the lab was Hiroaki Kawasaki. Dr. Kawasaki was most likely fabricating the data and Dr. Taira either couldn't figure that out or he was complicit in this scam.
The question now is how much this impacts the origins of the science. Does this leave a gap open where Dicers role is not known as a fact. Dr. Taira was saying that he could use recombinant Dicer to make siRNA that will work so that you don't have to experiment with different pieces to find the best one. This is one of his pre-conceived conclusions anyway. However, has anyone ever cloned dicer and shown it to chop up dsRNA? What type of dsRNA modifications are needed for Dicer to grab ahold of it and chop it up. Certainly Dicer isn't running amok inside a cell grabbing any dsRNA it finds and chopping it up. If it did we'd have a hard time making proteins. What regulates the balance between dsRNA breakdown and mRNA protein production? There are many enzymes that are very well understood. We use them for chopping up DNA for cloning genes. We know exactly where they cut the DNA. Where does Dicer cut the DNA? Is it based on size? If it is, then how does the siRNA shut down the genes so specifically. We know that synthisized RNA is a hit or miss gamble. Somehow one enzyme gets it right in many many different genes. How can this be.
This is science. How does siRNA work. What are the unanswered questions? What tiny little piece of the puzzle can we study? Dr. Taira is rightfully getting his work put under a spotlight. What about putting a spotlight on the research area he was working on. Why did they have to lie? Certainly it's important for these guys to publish but why didn't the area they were working on give them the kind of results they wanted? This is the Feynman Cargo Cult edict of bending over backwards to prove oneself wrong. They inadvertantly proved that they could not do what they thought they could do. They were ranked #4 in the siRNA business. In the end their theory did not provide them with the knowledge it would take to simply clone an enzyme and characterize it. Something is wrong here.
siRNA has been in existance a relatively short period of time. As soon as it began however, scientist began positioning themselves into the leadership role. There were rules set up for how to design siRNA. There were papers written on the best way to get the most out of your siRNA knock-out. Like a Cargo Cult Airport however, it wasn't known how siRNA really worked. The experts seemed have a disdain for research that involved a mechanism of action. One of "the rules" for example was that the siRNA had to consist of a certain percentage gaunisine and cytosine. What was the data used to come to that conclusion? Five siRNA KOs? Ten? Were they in mice or hamsters?
Eventually the scientists have to come up with a MOA, mechanism of action. It has been decided that the mechanism of action involves mRNA interacting with an enzyme called Dicer. One of the leading siRNA researchers, Dr. Kazunari Taira of the University of Tokyo describes it this way:
The mechanism responsible for dsRNA-induced gene silencing, which proceeds via a two-step mechanism, appears to have been strongly conserved during evolution. In the first step, long dsRNAs are recognized by a nuclease in the RNase III family known as Dicer, which cleaves the dsRNA into small interfering RNAs (siRNAs) of 21–23 nt. These siRNAs are incorporated into a multicomponent nuclease complex, known as RISC, that is then responsible for the destruction of cognate mRNAs.
Dr. Taira was a leader in siRNA research. More specifically he was ranked number 4 (most cited authors) out of the 25,000 researchers who have published papers on siRNA. He took on the toughest piece of the puzzle, the MOA and he got burned. A panel at the university where he worked said that he "likely fabricated papers on a potential medical breakthrough". As I've stated before, big time scientists do not work in laboratories. They work in offices. They communicate on the things that take place in labs but they rarely go inside their labs. One of the people who did work in the lab was Hiroaki Kawasaki. Dr. Kawasaki was most likely fabricating the data and Dr. Taira either couldn't figure that out or he was complicit in this scam.
The question now is how much this impacts the origins of the science. Does this leave a gap open where Dicers role is not known as a fact. Dr. Taira was saying that he could use recombinant Dicer to make siRNA that will work so that you don't have to experiment with different pieces to find the best one. This is one of his pre-conceived conclusions anyway. However, has anyone ever cloned dicer and shown it to chop up dsRNA? What type of dsRNA modifications are needed for Dicer to grab ahold of it and chop it up. Certainly Dicer isn't running amok inside a cell grabbing any dsRNA it finds and chopping it up. If it did we'd have a hard time making proteins. What regulates the balance between dsRNA breakdown and mRNA protein production? There are many enzymes that are very well understood. We use them for chopping up DNA for cloning genes. We know exactly where they cut the DNA. Where does Dicer cut the DNA? Is it based on size? If it is, then how does the siRNA shut down the genes so specifically. We know that synthisized RNA is a hit or miss gamble. Somehow one enzyme gets it right in many many different genes. How can this be.
This is science. How does siRNA work. What are the unanswered questions? What tiny little piece of the puzzle can we study? Dr. Taira is rightfully getting his work put under a spotlight. What about putting a spotlight on the research area he was working on. Why did they have to lie? Certainly it's important for these guys to publish but why didn't the area they were working on give them the kind of results they wanted? This is the Feynman Cargo Cult edict of bending over backwards to prove oneself wrong. They inadvertantly proved that they could not do what they thought they could do. They were ranked #4 in the siRNA business. In the end their theory did not provide them with the knowledge it would take to simply clone an enzyme and characterize it. Something is wrong here.
Sunday, June 04, 2006
Poetry
Charles Bukowski worked for the Post Office. He would do his job and come home and drink wine and write poetry. He didn't care much for his day job but he loved staying up late drinking alone, listening to classical music on the radio and typing out poems. His canvas was a white sheet of paper shoved into an old type writer. The demons running around inside his head provided excellent material for his work. He was mad and said so. He wasn't trying to hide it. He was trying to tell someone about it in case someone wanted to help.
Those of us who love Bukowskis work refer to the man as Hank. Hank was a grizzly bear of a man. He loved to drink. He loved women. He hated working. Down at the post office you had to do what you're told. You had to take tests putting letters into slots based on the addresses on the envelopes. There were bad bosses and co-workers to deal with. One day Hanks publisher told him to quit the post office job. They worked out the amount of money needed to support Hanks lifestyle and it was provided by the publisher. It amounted to something like 105 dollars a month for rent, food, booze and cigarettes. At the age of 50 he quit his job and became a professional writer. Within the month he had written his first novel. He wrote several more novels and hundreds of poems. The novels served as background material that helped the reader understand where some of those poems were coming from. At the end of his life there was a body of work that came together and told a story.
I'd like to fashion this blog after people like Bukowski. I'd like to bring up the beatniks. In college they teach science and they teach art. So far it's been the arts that have allowed outsiders to make an impact on society. Bukowski was a postal worker. Kerouac was a vagabond. One thing the best of them all shared was a lack of formal education. They wanted to write so they did. A scientist however will have a hard time in the modern realm of the business. Many physical scientists for example, have a hard time renting the time on an atom smasher to prove their theories. It costs money. Writing a book does not. So what I'm trying to do with this blog is create a place where beatnik thinkers can contemplate the possibilities of the natural world. That's not science of the latest fashion. It's science that applied to people who existed in medieval times. Lacking the ability to smash atoms or look at cells left people with no other options than to dream up possibilities. Imagination was king. As I've mentioned before, marketing is now king in science.
Step away from the kings of science and sketch out a possibility that you've been thinking about for awhile. Go to the local pub and sit at a table by yourself and write a long paper that you won't have to worry about getting published. Invent a start-up company in your head and don't worry about the investors. The business of science is run by people who are the best at getting promoted. The best scientists are probably sitting at lab benches all day wondering about the data they get and how it really happens. They don't believe much of the hype coming out of the labs they work in but they are keenly interested in the experiements. The big time scientists have a story they need to tell and they are only excepting data that helps tell that story. The small time scientists are like poets. They wonder about the world they live in. They just don't know how to get anywhere with their ideas so they hold them in. To the poets of science I say, let it out. Write it down. Start a blog. Start a journal. Seek out other disgruntled workers and use your anger to strike at the status quo. Do something to them that they never did for you. Make them think. Make sure that at the end of your life there is a body of work that people can use.
Those of us who love Bukowskis work refer to the man as Hank. Hank was a grizzly bear of a man. He loved to drink. He loved women. He hated working. Down at the post office you had to do what you're told. You had to take tests putting letters into slots based on the addresses on the envelopes. There were bad bosses and co-workers to deal with. One day Hanks publisher told him to quit the post office job. They worked out the amount of money needed to support Hanks lifestyle and it was provided by the publisher. It amounted to something like 105 dollars a month for rent, food, booze and cigarettes. At the age of 50 he quit his job and became a professional writer. Within the month he had written his first novel. He wrote several more novels and hundreds of poems. The novels served as background material that helped the reader understand where some of those poems were coming from. At the end of his life there was a body of work that came together and told a story.
I'd like to fashion this blog after people like Bukowski. I'd like to bring up the beatniks. In college they teach science and they teach art. So far it's been the arts that have allowed outsiders to make an impact on society. Bukowski was a postal worker. Kerouac was a vagabond. One thing the best of them all shared was a lack of formal education. They wanted to write so they did. A scientist however will have a hard time in the modern realm of the business. Many physical scientists for example, have a hard time renting the time on an atom smasher to prove their theories. It costs money. Writing a book does not. So what I'm trying to do with this blog is create a place where beatnik thinkers can contemplate the possibilities of the natural world. That's not science of the latest fashion. It's science that applied to people who existed in medieval times. Lacking the ability to smash atoms or look at cells left people with no other options than to dream up possibilities. Imagination was king. As I've mentioned before, marketing is now king in science.
Step away from the kings of science and sketch out a possibility that you've been thinking about for awhile. Go to the local pub and sit at a table by yourself and write a long paper that you won't have to worry about getting published. Invent a start-up company in your head and don't worry about the investors. The business of science is run by people who are the best at getting promoted. The best scientists are probably sitting at lab benches all day wondering about the data they get and how it really happens. They don't believe much of the hype coming out of the labs they work in but they are keenly interested in the experiements. The big time scientists have a story they need to tell and they are only excepting data that helps tell that story. The small time scientists are like poets. They wonder about the world they live in. They just don't know how to get anywhere with their ideas so they hold them in. To the poets of science I say, let it out. Write it down. Start a blog. Start a journal. Seek out other disgruntled workers and use your anger to strike at the status quo. Do something to them that they never did for you. Make them think. Make sure that at the end of your life there is a body of work that people can use.
Tuesday, May 23, 2006
Marketing Skills
Let's go all the way back to the very first post on this blog. I talked about Koreas number one scientist, Dr. Hwang. He became number one because of his skills in the ways of cloning stem cells. It turned out that he had, in fact, not cloned one single stem cell. No big deal, no one has succeeded at this little task. The big deal is that he was hell bent on telling everyone he had. Why did he want to do this? Most likely it was about ego or an exterior pressure to succeed. Whatever it was Dr. Hwang knew he had to overcome his inability to clone stem cells. Science tells us that it should be possible to do so. Technology is now the hard part. Instead of working on the hard part Dr. Hwang decided to use his marketing skills to sell his story to a major science journal.
How could a journal that calls itself Science have been sold this story? The name Science would indicate that they come to their conclusions based upon experimentation and observation. A journal is in a tough spot here because they can't take a paper such as Dr. Hwangs and simply repeat his work. They can't take a clone from him and seqeunce the DNA to verify the clone status. They have no choice but to rely upon what he has said. Of course arogance plays a part in the inability of the reviewers and the editors to admit their limitations. They will have us believe that most of what you are reading is solid science and it makes damned good sense. But how do they know? They were wrong about Dr. Hwang. He fooled them with his marketing skills. How can the editors and the reviewers tell the difference between real science and a marketing campaign? How can they tell the difference between shit and shinola?
The Cargo Cults of the world will never bring the planes from the skies using their current methods. If however you moved them to an area of the world where there is an airport, they would have much more success with their methods. The planes would come. You are now working in the wolrd of marketing. You want the world to believe that your rituals brings airplanes from the skies. All you have to do is perform the rituals with an airport behind you. Ritual plus airplanes equals success! You don't know a damned thing about how those airplanes end up coming from the sky to the field behind you. You know that they come however and you have put yourself in the right position to "prove" your skills.
Now look at Dr. Hwang. Rather than use science he published a ficticious paper in a magazine called Science. If it's in Science then it's science.
A very similar scenario took place in a publication that covers a softer science, Sociology. The journal was called Social Text. The paper was called Transgressing the Boundaries: Toward a Transformative Hermeneutics of Quantum Gravity. The author, Dr. Sokal, had a different motive than Dr. Hwang but let's not let our biases get in the way of comparing these two cases. They both had a motive to publish a paper that depicts complete rubbish. They both knew what they had to do to get published. It had to do with marketing. Dr. Sokal was thinking like a marketer.
"Would a leading North American journal of cultural studies... publish an article liberally salted with nonsense if (a) it sounded good and (b) it flattered the editors' ideological preconceptions?"
In other words, would they buy a bogus paper. (a) and (b) refer to the marketing skills.
Cloning a stem cell had the groundwork laid out for it to be marketed. Cloning stem cells sounds good. It would also verify the theory that this could be done. After the cloning techniques are worked out the skies the limit on what can be done. You could cure diabetes. No further treatments would be needed. You could clone a human being! We've cloned a sheep so this should be possible. It is exciting. It is the power of applying science to create life! This excitement is also a bias. The bias (a) sounded good and (b) flattered the editors' ideological preconceptions."
As I said earlier, the journals are in a tough spot if they are to publish articles based on their ability to see past marketing skills. They cannot reproduce the experiments that are written about. A real science journal would however. The CounterCargoCulture publication would handle the problem of marketing by reproducing experiments. It would demand DNA samples and cell cultures and whatever else is used to make a claim. This science journal would really look at the experiment and worry less about the marketing of it. If you've ever seen what PhD students study and what goes on with a disertation you know that marketing is what it is all about. They are preparing to go out and be published so they can live the life of their professor/mentor, publish or parish. A real science journal would acknowledge this bias and demand real proof behind the mere conclusions written up in a paper. The number of papers would be reduced to one per publication. Every little piece of evidence will be discussed philisophically and empirically. In the end the conclusions of a group of reviewers will be published. Each reviewer will not be allowed to discuss their conclusions with the other reviewers until after publication. Again, this is to reduce the bias imposed on you by others. In general a real science journal would take every measure possible to remove bias. Marketers exploit our biases in ways we have never even thought about. A real science journal must think like a marketer and stop them from contaminating the scientific discourse among critical thinking human beings.
How could a journal that calls itself Science have been sold this story? The name Science would indicate that they come to their conclusions based upon experimentation and observation. A journal is in a tough spot here because they can't take a paper such as Dr. Hwangs and simply repeat his work. They can't take a clone from him and seqeunce the DNA to verify the clone status. They have no choice but to rely upon what he has said. Of course arogance plays a part in the inability of the reviewers and the editors to admit their limitations. They will have us believe that most of what you are reading is solid science and it makes damned good sense. But how do they know? They were wrong about Dr. Hwang. He fooled them with his marketing skills. How can the editors and the reviewers tell the difference between real science and a marketing campaign? How can they tell the difference between shit and shinola?
The Cargo Cults of the world will never bring the planes from the skies using their current methods. If however you moved them to an area of the world where there is an airport, they would have much more success with their methods. The planes would come. You are now working in the wolrd of marketing. You want the world to believe that your rituals brings airplanes from the skies. All you have to do is perform the rituals with an airport behind you. Ritual plus airplanes equals success! You don't know a damned thing about how those airplanes end up coming from the sky to the field behind you. You know that they come however and you have put yourself in the right position to "prove" your skills.
Now look at Dr. Hwang. Rather than use science he published a ficticious paper in a magazine called Science. If it's in Science then it's science.
A very similar scenario took place in a publication that covers a softer science, Sociology. The journal was called Social Text. The paper was called Transgressing the Boundaries: Toward a Transformative Hermeneutics of Quantum Gravity. The author, Dr. Sokal, had a different motive than Dr. Hwang but let's not let our biases get in the way of comparing these two cases. They both had a motive to publish a paper that depicts complete rubbish. They both knew what they had to do to get published. It had to do with marketing. Dr. Sokal was thinking like a marketer.
"Would a leading North American journal of cultural studies... publish an article liberally salted with nonsense if (a) it sounded good and (b) it flattered the editors' ideological preconceptions?"
In other words, would they buy a bogus paper. (a) and (b) refer to the marketing skills.
Cloning a stem cell had the groundwork laid out for it to be marketed. Cloning stem cells sounds good. It would also verify the theory that this could be done. After the cloning techniques are worked out the skies the limit on what can be done. You could cure diabetes. No further treatments would be needed. You could clone a human being! We've cloned a sheep so this should be possible. It is exciting. It is the power of applying science to create life! This excitement is also a bias. The bias (a) sounded good and (b) flattered the editors' ideological preconceptions."
As I said earlier, the journals are in a tough spot if they are to publish articles based on their ability to see past marketing skills. They cannot reproduce the experiments that are written about. A real science journal would however. The CounterCargoCulture publication would handle the problem of marketing by reproducing experiments. It would demand DNA samples and cell cultures and whatever else is used to make a claim. This science journal would really look at the experiment and worry less about the marketing of it. If you've ever seen what PhD students study and what goes on with a disertation you know that marketing is what it is all about. They are preparing to go out and be published so they can live the life of their professor/mentor, publish or parish. A real science journal would acknowledge this bias and demand real proof behind the mere conclusions written up in a paper. The number of papers would be reduced to one per publication. Every little piece of evidence will be discussed philisophically and empirically. In the end the conclusions of a group of reviewers will be published. Each reviewer will not be allowed to discuss their conclusions with the other reviewers until after publication. Again, this is to reduce the bias imposed on you by others. In general a real science journal would take every measure possible to remove bias. Marketers exploit our biases in ways we have never even thought about. A real science journal must think like a marketer and stop them from contaminating the scientific discourse among critical thinking human beings.
Saturday, May 20, 2006
Counter-Cargo-Cult-ture
Get it? Counter-culture? The counter to the cargo cult? Like a beatnik or a hippy, there have to be scientists out there who would love to get away from the culture of modern day science. Where are the radical scientists who believe in the aneuploidy-cancer hypothesis? Where are the scientists who pursue ideas that are untested. One norm in biotech science these days involves looking for antibodies against known targets and patenting your antibody as a drug against the known disease. Another norm involves using siRNA in the same manner, to eliminate a known target protein. That just doesn't rise to the level of science. It's more like baking cookies. Someone may have a good recipe but it doesn't involve too much clever thinking. Intellectually there have got to be people starving to death due to a lack of interesting projects to think about. Where are the goddamned scientists who can think up their own projects? Chances are, those types of people are horrible at getting funding. Going out and getting government grants or venture capital money is not an interesting thing to roll around your brain unless you are more interested in money than in the natural world.
There has always been a counter culture. Early caveman drawings were probably countered by young people with cheap materials smeared on cave walls where only young cave people gathered. Perhaps this is an important part of the evolution of ideas. Good ideas start but are quickly taken over by the powers that be. Only the young and older, off-center, people venture to make changes to the status quo. If you have a stake in maintaining the status quo, such as having a hefty mortgage, you'll do what the group is doing in order to keep your house. If you don't feel included in the group or you don't want to be a part of it, you'll work against the tide. Maybe you'll protest the war, you'll write a book without first obtaining a PhD in english, you'll quit eating meat, you'll take up Buddhism in a Christian society, you'll take up Christianity in a Buddhist society, you'll be a scientist in a religious society...
Here is a simple example of changing the thinking surrounding the norm. I've mentioned siRNA research before. Has anyone ever thought about the consequences of the proposed mechanism of action? The second law of thermodynamics suggests that if order is created in one part of the universe then a greater amount of disorder is created somewhere else. In siRNA then, what happens if you knock down the activity of a protein? The popular concept is that the only possible outcome is that a person becomes healthier. What is the most lethal siRNA? Is it a 20 nucleotide sequence that will kill C-elagans? Is it a double stranded piece of RNA with a hairpin loop that will prevent ears of corn from growing out of a stalk? Most of the status quo research in this field involves known targets, siRNA selected by internet based tools, and low paid technicians. Who would have the guts to make a grant proposal where you claim you are going to seek out deadly siRNA. Maybe you want to create a cancer by stopping a cell cycle regulator. Maybe you just don't know exactly where you're going but you are going to start with stem cells and some gene mutation tools.
Radical science, like radical youth movements, is going to be discouraged by those who have established the norm or at least by those who benifit from the norm. Imagine living in Alabama in 1964, your hair is trimmed nicely, your glasses the latest fashion, your clothes sharp like everyone else around you. Then one day Ken Kesey and the Merry Pranksters drive through your town. They are traveling in an old school bus painted in a hundred bright colors. They are dressed as jesters and fairies throwing flowers and blowing bubbles. They don't have jobs to go to. Yet they are living life in America. They are seeing your town where you will probably never see theirs. You have to ask yourself, is their way of living meaningful? Chances are, having grown up in a small Alabama town, you prefer your ways. You like having a job and a family that you support. You are clean and safe. You travel a couple times a year but you get to come home to a stable world that you like. Who are these hippies to come around here being different, jumping around as if they are here to show us a better way of living? Your kids however might see it as a new and exciting prospect. They are secure in their world so they can come back if they don't like the new way. There is an alternative lifestyle that they can try. There is no harm in trying new things.
Now imagine an old scientist. He works at the University, he writes grant proposals, teaches classes and does a little research. He submits papers, reviews papers, serves on PhD committees and all of the other stuff. Along comes a kid whose parents left him a billion dollars. He skips college and starts his own lab where he does research to prove HIV doesn't cause AIDS. He brings in Peter Duesburg and supports his work on the aneuploidy-cancer hypothesis. He starts his own journal because no one else will publish him. He starts a philosophy organisation that discusses how things like N-rays or anything that Robert Gallo ever did could happen. All of the grad students can be found reading the journal in spite of your efforts to put it down. One day something useful comes out of the lab and the journal. Big deal you think, anyone can get lucky. Your young grad students might be tempted to go off on the new path but if they know what's best they'll stay with you. Maybe they'll be gone for awhile but they'll be back. You offer the safety just like the family man with a good job in Alabama. The counter culture is reckless.
The system is currently set up such that it really would take a rich kid with a billion dollars and an interest in science to overcome the obstacles in the way of a radical science movement. Most rich kids these days however are not science kids. Their positions in society lead them to other pursuits. They may become philanthropists but they will only support the status quo. They may become capitalists but they too only support the status quo. The status quo dictates that lots of money must be spent to do science and it must lead to the generation of more money. I've mentioned how biotech has taken 100 billion and reduced it to 60 billion so far. As in any Cargo Cult, the lack of success does not deter the followers and those in charge. The counter cult would simply seek out advances in understanding of living organisms. They would work to accurately measure what is going on inside the body. There would be no need for profit, just pure joy in discovering new things. Of course in the end there would be much that could be commercialized but the hippy scientist would not be interested. He's got a billion dollar padding that prevents him from commercial influence. He's got a disdain for suits and ties making shit up so they can sell drugs.
The radical science would not require as much money. I just threw a billion dollars out there to make us all feel safe. Ideas are more powerful than money if they are based on fact. Radical science would become the target of criticism by some of our best critics. Yet imagine a movement where an explanation for the 40 billion dollars loss in biotech could be analyzed. Imagine aneuploidy research explaining a very basic concept in cancer. Imagine a bunch of young people sitting around reducing the status quo science down to easy to understand concepts that have flaws. Imagine young people getting excited about science because there is a counter culture that has the ability to chop down the tall trees in a forest of arrogant old ideas.
Imagine old Bob Gallo, picking lint from his pin striped suit as he tells everyone how he was the most cited scientist of his day. Along comes a young kid in jeans and a T-shirt who points out that Bob was wrong and that he lead a lot of people to the wrong conclusions. The young kid has cured AIDS and has shown that the emperor (Bob) has no clothes. AIDS, cancer, malaria, alzheimers, baldness, and the list goes on. These are things that science doesn't have a clue about. They are on a path that involves simple concepts wrapped in hard to understand terminology that arrogant men and women love to use. A counter culture is needed to bring life back into the world of science. Excitement is needed. Currently it is dying. Money is the goal and failure is the result. We need that billion dollar kid willing to support this cause. Think of that billion dollar investment as Ken Keseys bus. The billion dollar radical science movement might just fizzle out but for young people it could symbolize the freedom to think again. You take that education they give you and get rid of the things you think are bullshit. Think your own thoughts and nevermind what the elders say.
There has always been a counter culture. Early caveman drawings were probably countered by young people with cheap materials smeared on cave walls where only young cave people gathered. Perhaps this is an important part of the evolution of ideas. Good ideas start but are quickly taken over by the powers that be. Only the young and older, off-center, people venture to make changes to the status quo. If you have a stake in maintaining the status quo, such as having a hefty mortgage, you'll do what the group is doing in order to keep your house. If you don't feel included in the group or you don't want to be a part of it, you'll work against the tide. Maybe you'll protest the war, you'll write a book without first obtaining a PhD in english, you'll quit eating meat, you'll take up Buddhism in a Christian society, you'll take up Christianity in a Buddhist society, you'll be a scientist in a religious society...
Here is a simple example of changing the thinking surrounding the norm. I've mentioned siRNA research before. Has anyone ever thought about the consequences of the proposed mechanism of action? The second law of thermodynamics suggests that if order is created in one part of the universe then a greater amount of disorder is created somewhere else. In siRNA then, what happens if you knock down the activity of a protein? The popular concept is that the only possible outcome is that a person becomes healthier. What is the most lethal siRNA? Is it a 20 nucleotide sequence that will kill C-elagans? Is it a double stranded piece of RNA with a hairpin loop that will prevent ears of corn from growing out of a stalk? Most of the status quo research in this field involves known targets, siRNA selected by internet based tools, and low paid technicians. Who would have the guts to make a grant proposal where you claim you are going to seek out deadly siRNA. Maybe you want to create a cancer by stopping a cell cycle regulator. Maybe you just don't know exactly where you're going but you are going to start with stem cells and some gene mutation tools.
Radical science, like radical youth movements, is going to be discouraged by those who have established the norm or at least by those who benifit from the norm. Imagine living in Alabama in 1964, your hair is trimmed nicely, your glasses the latest fashion, your clothes sharp like everyone else around you. Then one day Ken Kesey and the Merry Pranksters drive through your town. They are traveling in an old school bus painted in a hundred bright colors. They are dressed as jesters and fairies throwing flowers and blowing bubbles. They don't have jobs to go to. Yet they are living life in America. They are seeing your town where you will probably never see theirs. You have to ask yourself, is their way of living meaningful? Chances are, having grown up in a small Alabama town, you prefer your ways. You like having a job and a family that you support. You are clean and safe. You travel a couple times a year but you get to come home to a stable world that you like. Who are these hippies to come around here being different, jumping around as if they are here to show us a better way of living? Your kids however might see it as a new and exciting prospect. They are secure in their world so they can come back if they don't like the new way. There is an alternative lifestyle that they can try. There is no harm in trying new things.
Now imagine an old scientist. He works at the University, he writes grant proposals, teaches classes and does a little research. He submits papers, reviews papers, serves on PhD committees and all of the other stuff. Along comes a kid whose parents left him a billion dollars. He skips college and starts his own lab where he does research to prove HIV doesn't cause AIDS. He brings in Peter Duesburg and supports his work on the aneuploidy-cancer hypothesis. He starts his own journal because no one else will publish him. He starts a philosophy organisation that discusses how things like N-rays or anything that Robert Gallo ever did could happen. All of the grad students can be found reading the journal in spite of your efforts to put it down. One day something useful comes out of the lab and the journal. Big deal you think, anyone can get lucky. Your young grad students might be tempted to go off on the new path but if they know what's best they'll stay with you. Maybe they'll be gone for awhile but they'll be back. You offer the safety just like the family man with a good job in Alabama. The counter culture is reckless.
The system is currently set up such that it really would take a rich kid with a billion dollars and an interest in science to overcome the obstacles in the way of a radical science movement. Most rich kids these days however are not science kids. Their positions in society lead them to other pursuits. They may become philanthropists but they will only support the status quo. They may become capitalists but they too only support the status quo. The status quo dictates that lots of money must be spent to do science and it must lead to the generation of more money. I've mentioned how biotech has taken 100 billion and reduced it to 60 billion so far. As in any Cargo Cult, the lack of success does not deter the followers and those in charge. The counter cult would simply seek out advances in understanding of living organisms. They would work to accurately measure what is going on inside the body. There would be no need for profit, just pure joy in discovering new things. Of course in the end there would be much that could be commercialized but the hippy scientist would not be interested. He's got a billion dollar padding that prevents him from commercial influence. He's got a disdain for suits and ties making shit up so they can sell drugs.
The radical science would not require as much money. I just threw a billion dollars out there to make us all feel safe. Ideas are more powerful than money if they are based on fact. Radical science would become the target of criticism by some of our best critics. Yet imagine a movement where an explanation for the 40 billion dollars loss in biotech could be analyzed. Imagine aneuploidy research explaining a very basic concept in cancer. Imagine a bunch of young people sitting around reducing the status quo science down to easy to understand concepts that have flaws. Imagine young people getting excited about science because there is a counter culture that has the ability to chop down the tall trees in a forest of arrogant old ideas.
Imagine old Bob Gallo, picking lint from his pin striped suit as he tells everyone how he was the most cited scientist of his day. Along comes a young kid in jeans and a T-shirt who points out that Bob was wrong and that he lead a lot of people to the wrong conclusions. The young kid has cured AIDS and has shown that the emperor (Bob) has no clothes. AIDS, cancer, malaria, alzheimers, baldness, and the list goes on. These are things that science doesn't have a clue about. They are on a path that involves simple concepts wrapped in hard to understand terminology that arrogant men and women love to use. A counter culture is needed to bring life back into the world of science. Excitement is needed. Currently it is dying. Money is the goal and failure is the result. We need that billion dollar kid willing to support this cause. Think of that billion dollar investment as Ken Keseys bus. The billion dollar radical science movement might just fizzle out but for young people it could symbolize the freedom to think again. You take that education they give you and get rid of the things you think are bullshit. Think your own thoughts and nevermind what the elders say.
Monday, May 15, 2006
A Well Funded Cult
Working with the scientific method can be tough. Nature has a way of frustrating us human beings. To get around our ignorance we have created religions and we have created science. In between these two extremes there are varying degrees of getting the world to do what we want it to do. Say for example, you have cancer and you want it to go away. You could pray and it might go away. If it does you attribute the disappearance of the cancer to the praying. Likewise you could take a drug that is on the market. Again, if the cancer goes away, it's because of the drug. The problem is that we are only guessing. It could have gotten worse. What then becomes of our beliefs on prayer or the drug industry?
When drug companies run clinical trials they have many options for obtaining the best possible results. Like religion, they can work around evidence that detracts from their hypothesis. What can we do as consumers to varify if the drug companies are operating in a less than honest manner? We can use the scientific method.
TUESDAY, May 16 (HealthDay News) -- In a revealing look at the impact of funding on medical research, a new study found that clinical trials funded by drug companies and other for-profit entities were more likely to report positive findings than similar trials funded by nonprofit groups. ...according to background information in this article, surveys of randomized trials conducted in the 1990s found that for-profit trials were more likely to report positive findings. Those surveys raised questions about the design and conduct of industry-funded clinical trials. A study published earlier this year found that industry is paying for more and more medical research, with a full half of studies now funded solely by the private sector.
In this paper published in JAMA, May 17 2006, they looked at the data from 324 consecutive superiority trials of cardiovascular medicine published between January 1, 2000, and July 30, 2005, in JAMA, The Lancet, and the New England Journal of Medicine. The question was whether or not the trend of for-profit funded trials providing favorable results continued from 2000 to 2005. Since it is known that industry is paying for more and more research, we might want to take a closer look at the studies that are being conducted. If the drug companies are going to pay for the studies, we have to study the studies. We have to question the questions they are asking.
It's difficult to take a random sampling and come up with an exact description of what you've got. Say you you want to measure handfuls of dirt. You hire people all over the world to pick up a handful of dirt and analyse what they get. In China people have smaller hands than people in France. The French might report that their dirt weighs more than Chinese dirt. In Palm Springs where dirt is very dry they say that their dirt weighs less than the dirt in Nebraska. So already we've got problems in measuring the weight of a handful of dirt. How do we account for factors such as hand size and moisture content?
One way to analyse the results that get published is to look at who is doing the study. Do they want the dirt to weigh more or less? Maybe the French have already reported on the correlation of the weight of dirt and the annual production of crops. Lets say that an increase in the weight of dirt corralates with an increase in crop production. Palm Springs has a desire to introduce farming into their economy. The French make a pitch to sell them their dirt as do the Nebraskans. The Palm Spring folk see that the dirt from each group is roughly the same based on their studies. The Nebraskans protest with a study that they funded indicating that the French cheated by only using data from dirt picked up by men. Men have larger hands than women. The French tout a study that they conducted where the dirt in Nebraksa was picked up by Chinese women. Of course they don't mention that part of the study. The Nebraskans go after the scientific integrity of the French. Who do you believe? All this science is just so confusing.
As you can see, this can get out of control. The real issue that we've forgotten is whether or not the weight of dirt has anything to do with growing a crop. What is the crop anyway? Cactus? In order to get to the bottom of an issue in nature it is important to know what you are looking for. It is critical that the questions asked are non-biased.
In the same issue of JAMA there is a study on the cancer risks in taking HUMIRA and Remicade, both monoclonal antibodies against TNF alpha. The drugs are prescribed for treating rheumatoid arthritis. One of the authors, Eric L. Matteson, MD, MPH, is getting paid by the makers of another TNF alpha inhibitor (Enbrel) to do a similar analysis on Enbrel alone. The reason Enbrel was left out of the trial was because Enbrel differs at the molecular level. HUMRIA and Remicade are antibodies whereas Enbrel is a modified TNF alpha receptor. Should that really matter? Was this study fair? Before the article begins perhaps factors such as Dr. Mattesons relationship with the makers of a competitors drug should be divulged.
Dr. Matteson may or may not publish a similar article on Enbrel. The effects of this corporate study will be people switching from HUMIRA and Remicade to Enbrel. That's just a guess. To be fair however Enbrel needs to be put up to the same rigors of the HUMIRA/Remicade study. Ultimately we might find out the effects of TNF alpha levels. It is complicated but drug company motives are not. Study the studies. Look at what they are doing and make decisions based on their own research. Use their data to draw conclusions that they never intended you to draw. The more we learn about corporate science the better we'll be able to gauge their conclusions.
When drug companies run clinical trials they have many options for obtaining the best possible results. Like religion, they can work around evidence that detracts from their hypothesis. What can we do as consumers to varify if the drug companies are operating in a less than honest manner? We can use the scientific method.
TUESDAY, May 16 (HealthDay News) -- In a revealing look at the impact of funding on medical research, a new study found that clinical trials funded by drug companies and other for-profit entities were more likely to report positive findings than similar trials funded by nonprofit groups. ...according to background information in this article, surveys of randomized trials conducted in the 1990s found that for-profit trials were more likely to report positive findings. Those surveys raised questions about the design and conduct of industry-funded clinical trials. A study published earlier this year found that industry is paying for more and more medical research, with a full half of studies now funded solely by the private sector.
In this paper published in JAMA, May 17 2006, they looked at the data from 324 consecutive superiority trials of cardiovascular medicine published between January 1, 2000, and July 30, 2005, in JAMA, The Lancet, and the New England Journal of Medicine. The question was whether or not the trend of for-profit funded trials providing favorable results continued from 2000 to 2005. Since it is known that industry is paying for more and more research, we might want to take a closer look at the studies that are being conducted. If the drug companies are going to pay for the studies, we have to study the studies. We have to question the questions they are asking.
It's difficult to take a random sampling and come up with an exact description of what you've got. Say you you want to measure handfuls of dirt. You hire people all over the world to pick up a handful of dirt and analyse what they get. In China people have smaller hands than people in France. The French might report that their dirt weighs more than Chinese dirt. In Palm Springs where dirt is very dry they say that their dirt weighs less than the dirt in Nebraska. So already we've got problems in measuring the weight of a handful of dirt. How do we account for factors such as hand size and moisture content?
One way to analyse the results that get published is to look at who is doing the study. Do they want the dirt to weigh more or less? Maybe the French have already reported on the correlation of the weight of dirt and the annual production of crops. Lets say that an increase in the weight of dirt corralates with an increase in crop production. Palm Springs has a desire to introduce farming into their economy. The French make a pitch to sell them their dirt as do the Nebraskans. The Palm Spring folk see that the dirt from each group is roughly the same based on their studies. The Nebraskans protest with a study that they funded indicating that the French cheated by only using data from dirt picked up by men. Men have larger hands than women. The French tout a study that they conducted where the dirt in Nebraksa was picked up by Chinese women. Of course they don't mention that part of the study. The Nebraskans go after the scientific integrity of the French. Who do you believe? All this science is just so confusing.
As you can see, this can get out of control. The real issue that we've forgotten is whether or not the weight of dirt has anything to do with growing a crop. What is the crop anyway? Cactus? In order to get to the bottom of an issue in nature it is important to know what you are looking for. It is critical that the questions asked are non-biased.
In the same issue of JAMA there is a study on the cancer risks in taking HUMIRA and Remicade, both monoclonal antibodies against TNF alpha. The drugs are prescribed for treating rheumatoid arthritis. One of the authors, Eric L. Matteson, MD, MPH, is getting paid by the makers of another TNF alpha inhibitor (Enbrel) to do a similar analysis on Enbrel alone. The reason Enbrel was left out of the trial was because Enbrel differs at the molecular level. HUMRIA and Remicade are antibodies whereas Enbrel is a modified TNF alpha receptor. Should that really matter? Was this study fair? Before the article begins perhaps factors such as Dr. Mattesons relationship with the makers of a competitors drug should be divulged.
Dr. Matteson may or may not publish a similar article on Enbrel. The effects of this corporate study will be people switching from HUMIRA and Remicade to Enbrel. That's just a guess. To be fair however Enbrel needs to be put up to the same rigors of the HUMIRA/Remicade study. Ultimately we might find out the effects of TNF alpha levels. It is complicated but drug company motives are not. Study the studies. Look at what they are doing and make decisions based on their own research. Use their data to draw conclusions that they never intended you to draw. The more we learn about corporate science the better we'll be able to gauge their conclusions.
The Investment in People
Seattle Washington
5-15-06
Pacific Northwest Research Institute
Job Posting:
Assist in basic cancer research: cell culture; purification of proteins, lipids, nd other membrane components; molecular biology work (including RT-PCR, gene cloning); and other biochemical and biological assays. Position requires a B.S., basic lab skills in biochemistry, cell biology, molecular biology; and a familiarity with MS Word and Excel.
And what does it pay you ask?
23000 dollars per year!!!
Median price of a house in Seattle?
405000!!!
NIH budget?
28 billion 7 hundred and 40 million dollars
What percentage of the budget will go to that new graduate with the entry level job?
0.000008%
So put on that white lab coat and work til late in the night. You're doing it for nobility. Maybe you'll do it because you know someone who died from cancer and you want to help. Your next hurdle will be getting over a researcher who puts that value on the people wearing the white lab coats in his/her lab.
5-15-06
Pacific Northwest Research Institute
Job Posting:
Assist in basic cancer research: cell culture; purification of proteins, lipids, nd other membrane components; molecular biology work (including RT-PCR, gene cloning); and other biochemical and biological assays. Position requires a B.S., basic lab skills in biochemistry, cell biology, molecular biology; and a familiarity with MS Word and Excel.
And what does it pay you ask?
23000 dollars per year!!!
Median price of a house in Seattle?
405000!!!
NIH budget?
28 billion 7 hundred and 40 million dollars
What percentage of the budget will go to that new graduate with the entry level job?
0.000008%
So put on that white lab coat and work til late in the night. You're doing it for nobility. Maybe you'll do it because you know someone who died from cancer and you want to help. Your next hurdle will be getting over a researcher who puts that value on the people wearing the white lab coats in his/her lab.
Friday, May 12, 2006
Faith Healers
In a previous post I quoted Leigh Turner of McGill University Quebec as saying, "Biotech, in a similar manner to many religious movements, has its charismatic prophets, enthusiastic evangelists and enrapt audiences. Like religions, it offers a comforting message of salvation. Instead of imagining a day of rapture when the dead rise from their graves to begin eternal life, biotech enthusiasts imagine the era when medical technologies provide a renewable, largely imperishable body. … Biotech is not just an assemblage of research programs and techniques. In a scientific and technological era, biotech also offers a surrogate religious framework for many individuals."
I'd like to discuss two examples of this. The first one religious, and the second Biotech.
Benny Hinn is a faith healer. He makes a whole lot of money off of people who are desperate for Gods intervention into their problems. He recently had a gig over in Denmark where a young girl with a serious spinal condition attended.
From the James Randi webpage:
Unfortunately, the little girl with a damaged back did not regain her health – she had to drive home with her parents, disappointed. She did, however, have a more pronounced desire to stand up and walk than she had before. Somehow, I think her parents hoped more than she did. She never looked as if she believed anything would happen anyway. Which, in the Land of Faith Healing, means that she is to blame for Benny Hinn's failure. If you are cured, it is the work of God (through the faith healer). If you are not cured, it is because you haven't believed enough.
But desperation breeds hope, hope springs eternal, and hope will make people pay. The collection of money (cash, checks or plastic) in white buckets to fund these "crusades," while songs of the promise of upcoming miracles churned out from the stage, made it very clear: "Prosperity Teaching" means that you can be healed, but only if you pay up.
I believe that Benny Hinn is a bad guy. He's been exposed by James Randi. 20/20 ran a piece on him that showed just how much luxory he has wrapped himself in with the faithfuls money. He profits because he knows what people need to hear. He does not stop for any proof, he tells the masses what they want to hear and it sounds good to them.
Now! Biotech.
NeoRx has been around since 1984. This is a company that made the promise of curing cancer. Year after year they went to their investors (their faithful) and assured them that they were on the verge of something big. Hundreds of millions of dollars later, NeoRx is gone. The leaders however, have found a way to preserve the funding of their efforts. Since they did such a good job they will now be installing themselves into a Cargo Cult control room called Poinard Pharmaceuticals. The drug will be Picoplatin. As it is with all drug companies, the drug may or may not work. What matters is that the new companies big plan.
"NeoRx Corporation will formally change its corporate name to Poniard Pharmaceuticals, Inc. to reflect its strategic repositioning as a global specialty pharmaceutical company focused on the discovery, development and commercialization of innovative products to impact the lives of people with cancer."
That's important stuff. People with cancer need their lives impacted by innovative products. In addition to Picoplatin they are working to build a diverse portfolio of oncology product candidates. Did I mention that they've been in business since 1984?
Faith healers can make any promise that people want to hear. Want a cure for cancer? You got it. Spinal cord not working? It'll be fixed. There is no limit to what they can promise to do. They can promise that all sorts of airplanes will be coming to their Cargo Cult Airport but so far none have come. Benny Hinn and NeoRx have been around since at least 1984. Before that they were developing their strategy to become successful. They have been out there in front the faithful preaching the good news and they are still alive. They have succeeded. Whether the money was stuffed into a white bucket or transferred from a TD Waterhouse account, the money went to where the faith healers wanted it. It went into their livelihoods. Nice hotels, luxory cars, new clothes and ever increasing bank accounts have all been their rewards. If you don't have any faith in them it doesn't matter. They survive on the resources of their believers.
I'd like to discuss two examples of this. The first one religious, and the second Biotech.
Benny Hinn is a faith healer. He makes a whole lot of money off of people who are desperate for Gods intervention into their problems. He recently had a gig over in Denmark where a young girl with a serious spinal condition attended.
From the James Randi webpage:
Unfortunately, the little girl with a damaged back did not regain her health – she had to drive home with her parents, disappointed. She did, however, have a more pronounced desire to stand up and walk than she had before. Somehow, I think her parents hoped more than she did. She never looked as if she believed anything would happen anyway. Which, in the Land of Faith Healing, means that she is to blame for Benny Hinn's failure. If you are cured, it is the work of God (through the faith healer). If you are not cured, it is because you haven't believed enough.
But desperation breeds hope, hope springs eternal, and hope will make people pay. The collection of money (cash, checks or plastic) in white buckets to fund these "crusades," while songs of the promise of upcoming miracles churned out from the stage, made it very clear: "Prosperity Teaching" means that you can be healed, but only if you pay up.
I believe that Benny Hinn is a bad guy. He's been exposed by James Randi. 20/20 ran a piece on him that showed just how much luxory he has wrapped himself in with the faithfuls money. He profits because he knows what people need to hear. He does not stop for any proof, he tells the masses what they want to hear and it sounds good to them.
Now! Biotech.
NeoRx has been around since 1984. This is a company that made the promise of curing cancer. Year after year they went to their investors (their faithful) and assured them that they were on the verge of something big. Hundreds of millions of dollars later, NeoRx is gone. The leaders however, have found a way to preserve the funding of their efforts. Since they did such a good job they will now be installing themselves into a Cargo Cult control room called Poinard Pharmaceuticals. The drug will be Picoplatin. As it is with all drug companies, the drug may or may not work. What matters is that the new companies big plan.
"NeoRx Corporation will formally change its corporate name to Poniard Pharmaceuticals, Inc. to reflect its strategic repositioning as a global specialty pharmaceutical company focused on the discovery, development and commercialization of innovative products to impact the lives of people with cancer."
That's important stuff. People with cancer need their lives impacted by innovative products. In addition to Picoplatin they are working to build a diverse portfolio of oncology product candidates. Did I mention that they've been in business since 1984?
Faith healers can make any promise that people want to hear. Want a cure for cancer? You got it. Spinal cord not working? It'll be fixed. There is no limit to what they can promise to do. They can promise that all sorts of airplanes will be coming to their Cargo Cult Airport but so far none have come. Benny Hinn and NeoRx have been around since at least 1984. Before that they were developing their strategy to become successful. They have been out there in front the faithful preaching the good news and they are still alive. They have succeeded. Whether the money was stuffed into a white bucket or transferred from a TD Waterhouse account, the money went to where the faith healers wanted it. It went into their livelihoods. Nice hotels, luxory cars, new clothes and ever increasing bank accounts have all been their rewards. If you don't have any faith in them it doesn't matter. They survive on the resources of their believers.
Thursday, May 11, 2006
The Flu In Big Trouble
Don't worry about the avian flu everybody. It messed with the wrong group this time. Them dumb birds aint got no scientists among them to fight back. But we do! So go ahead flu, come and get us humans. We got scientists!
There is biotech company that is working on a way of dealing with this pending pandemic. Our old friend siRNA is going to prevent the flu from replicating once it gets inside our bodies. The pandemic will work this way: the virus becomes infectious, hospitals begin to report cases to the public, panic will set in among the masses, the siRNA drug will be dispersed, the virus will dissapear and that little biotech company will become filthy rich! Now why didn't anyone else think of matching siRNA technology with the biggest health scare in recent history?
"In vitro and in vivo results were presented for siRNAs that are specifically designed to target conserved regions of the influenza viral genome."
Conserved regions are stretches of a DNA sequence that are the same among a variety of DNA genomes. In the case of the flu, conserved regions are conserved as the various strains arise from season to season. In other words, strains of the virus arise as the result of mutations. Conserved regions have not been subjected to mutations for many many seasons.
"We believe that targeting the conserved regions could enable a siRNA therapeutic to be effective against both current and future strains of the influenza virus, which is essential in stockpiling a treatment for rapid mobilization during an influenza pandemic."
We're not just going to fight the avian flu virus, we're going to fight them all. Each year they come at us, we're going to knock them out. Avian flu? You want some of this? What about the Spanish flu of the 1918 pandemic? Come on back! Thanks to conserved regions of DNA, we've got them all by the balls. Think of conserved regions as the Achilles heal of the virus world. The only weapon against that heal is siRNA.
The company that will be putting an end to the influenza problem is not very big. We'll call them Company A to avoid any lawsuits. How big is Company A? Pfizer, who lists itself as the worlds largest pharmaceutical company, employs over 115,000 people. The slayers of influenza have about 100 people. Of those 100, less than half work in the science end of the business. Of that half less than ten work directly on the avian flu project. Of that group of less than ten, most sit in on meetings and listen to the results of experiments and try to put together a story to tell their superiors regarding the progress of the work.
How did it all begin? Company A needed to find a new siRNA project. The drug target TNF alpha (for cancer and inflammation) has several drugs on the market already. By using the siRNA, Company A assumed they had a way around the patents against TNF alpha. They soon found out that they would not be going far with this project. They spent a lot of time on the issues of delivery and assay development. When they finally ran a mouse experiment with 300 mice, they knew their goose was cooked. They tried again. Same results, nothing. They changed the dose, the delivery reagents, the mice, the RNA sequence and on and on until they just couldn't face the future. They needed a smoke screen. It had to be an siRNA smoke screen so they could claim to be continuing on with their "siRNA program". That's a lot easier than saying that you are ending the damned thing. Enter siRNA against the avian flu virus.
Company A did not have the time to go back and use their research methods against a conserved region of the influenza virus. They found a "company" that had already been on the case. A research scientist from MIT had begun the "company" after his academic lab had made some findings that allowed him to sell the technology. He received funding and a "company" was formed. We'll call that Company B. Company B obtained enough preliminary data to sell the license to Company A. Company A announce the acquisition of company B on 2-23-06. On 3-16-06 presentated results demonstrating the effectiveness of the Company's small interfering RNA (siRNA) therapeutics to broadly target and inhibit influenza viral production. With a little bit of money and some clever talent scouting, Company A turned their siRNA research around in one month.
Now... will it put up a good fight against the influenza virus? I'm going to stop writing about it now but I will come back to you later with some results that can answer that question. Unlike the scientists who are fighting the influenza virus with siRNA, I am an observer. I have no money to be gained or lost. This is science. I admit my bias. I don't think it will work. I believe that millions will be spent and many a PhD will work long days on the project. In the end it will fade away. Stay tuned.
P.S. Job Posting 5-8-06
Company A is seeking a highly skilled virologist with a good understanding of drug discovery and development to join our team. This position requires an experienced bench virologist with a comprehensive knowledge of influenza and other respiratory viruses including viral research in an industrial setting; broad knowledge of viral assay methods, screening and characterizing anti-viral drug compounds, drug delivery methods, pulmonary delivery, and in vitro and in vivo studies to determine efficacy of anti-viral compounds. For the exceptional individual this position has significant growth and leadership potential. In this role, you will lead virology projects involving RNAi research with a focus on the therapeutic development of siRNAs. Successful candidate will, supervise one or more research associates, provide scientific leadership and guidance for virology research programs, and collaborate with other team members in the identification and optimization of new siRNA anti-viral candidate therapeutics.Qualified candidates will have a Ph.D. in virology or related field with 3-5 years experience; industrial experience preferred. We are looking for a hands-on bench scientist with good analytical skills and management abilities. Must be an independent and critical thinker, experienced in leading project teams, perform well under heavy work loads, and possess excellent oral and written communication skills. Experience in RNAi research preferred.
There is biotech company that is working on a way of dealing with this pending pandemic. Our old friend siRNA is going to prevent the flu from replicating once it gets inside our bodies. The pandemic will work this way: the virus becomes infectious, hospitals begin to report cases to the public, panic will set in among the masses, the siRNA drug will be dispersed, the virus will dissapear and that little biotech company will become filthy rich! Now why didn't anyone else think of matching siRNA technology with the biggest health scare in recent history?
"In vitro and in vivo results were presented for siRNAs that are specifically designed to target conserved regions of the influenza viral genome."
Conserved regions are stretches of a DNA sequence that are the same among a variety of DNA genomes. In the case of the flu, conserved regions are conserved as the various strains arise from season to season. In other words, strains of the virus arise as the result of mutations. Conserved regions have not been subjected to mutations for many many seasons.
"We believe that targeting the conserved regions could enable a siRNA therapeutic to be effective against both current and future strains of the influenza virus, which is essential in stockpiling a treatment for rapid mobilization during an influenza pandemic."
We're not just going to fight the avian flu virus, we're going to fight them all. Each year they come at us, we're going to knock them out. Avian flu? You want some of this? What about the Spanish flu of the 1918 pandemic? Come on back! Thanks to conserved regions of DNA, we've got them all by the balls. Think of conserved regions as the Achilles heal of the virus world. The only weapon against that heal is siRNA.
The company that will be putting an end to the influenza problem is not very big. We'll call them Company A to avoid any lawsuits. How big is Company A? Pfizer, who lists itself as the worlds largest pharmaceutical company, employs over 115,000 people. The slayers of influenza have about 100 people. Of those 100, less than half work in the science end of the business. Of that half less than ten work directly on the avian flu project. Of that group of less than ten, most sit in on meetings and listen to the results of experiments and try to put together a story to tell their superiors regarding the progress of the work.
How did it all begin? Company A needed to find a new siRNA project. The drug target TNF alpha (for cancer and inflammation) has several drugs on the market already. By using the siRNA, Company A assumed they had a way around the patents against TNF alpha. They soon found out that they would not be going far with this project. They spent a lot of time on the issues of delivery and assay development. When they finally ran a mouse experiment with 300 mice, they knew their goose was cooked. They tried again. Same results, nothing. They changed the dose, the delivery reagents, the mice, the RNA sequence and on and on until they just couldn't face the future. They needed a smoke screen. It had to be an siRNA smoke screen so they could claim to be continuing on with their "siRNA program". That's a lot easier than saying that you are ending the damned thing. Enter siRNA against the avian flu virus.
Company A did not have the time to go back and use their research methods against a conserved region of the influenza virus. They found a "company" that had already been on the case. A research scientist from MIT had begun the "company" after his academic lab had made some findings that allowed him to sell the technology. He received funding and a "company" was formed. We'll call that Company B. Company B obtained enough preliminary data to sell the license to Company A. Company A announce the acquisition of company B on 2-23-06. On 3-16-06 presentated results demonstrating the effectiveness of the Company's small interfering RNA (siRNA) therapeutics to broadly target and inhibit influenza viral production. With a little bit of money and some clever talent scouting, Company A turned their siRNA research around in one month.
Now... will it put up a good fight against the influenza virus? I'm going to stop writing about it now but I will come back to you later with some results that can answer that question. Unlike the scientists who are fighting the influenza virus with siRNA, I am an observer. I have no money to be gained or lost. This is science. I admit my bias. I don't think it will work. I believe that millions will be spent and many a PhD will work long days on the project. In the end it will fade away. Stay tuned.
P.S. Job Posting 5-8-06
Company A is seeking a highly skilled virologist with a good understanding of drug discovery and development to join our team. This position requires an experienced bench virologist with a comprehensive knowledge of influenza and other respiratory viruses including viral research in an industrial setting; broad knowledge of viral assay methods, screening and characterizing anti-viral drug compounds, drug delivery methods, pulmonary delivery, and in vitro and in vivo studies to determine efficacy of anti-viral compounds. For the exceptional individual this position has significant growth and leadership potential. In this role, you will lead virology projects involving RNAi research with a focus on the therapeutic development of siRNAs. Successful candidate will, supervise one or more research associates, provide scientific leadership and guidance for virology research programs, and collaborate with other team members in the identification and optimization of new siRNA anti-viral candidate therapeutics.Qualified candidates will have a Ph.D. in virology or related field with 3-5 years experience; industrial experience preferred. We are looking for a hands-on bench scientist with good analytical skills and management abilities. Must be an independent and critical thinker, experienced in leading project teams, perform well under heavy work loads, and possess excellent oral and written communication skills. Experience in RNAi research preferred.
Wednesday, May 10, 2006
siRNA
There are trends in science. RNAi (short for RNA interference) is one of the latest trends. The story is that DNA makes RNA which makes proteins which make us. Since we have a hard time following a protein around and seeing what it's doing, we try to stop the protein from doing anything. In the past we have created "knock-out" mice, which lack the gene that codes for a protein. We have made antibodies go proteins so that they'll bind to and block the protein. We have thus been able to look at the world without the protein. What happens when a protein is taken out of the picture? Does the organism need it? Is it compensated for by the upregulation of another protein? RNAi is the latest tool in asking these types of questions. It is also much faster than making antidodies or knock-out mice.
There once was a Biotechnology company called Ribozyme Pharmaceuticals Inc. They failed. RNAi came along and they reinvented the company, "at the forefront of the effort to create RNAi-based therapies." They describe the technology as follows:
RNAi is a natural, selective process for turning off genes. RNAi is triggered by short interfering RNA (siRNA). An intermediate in the RNAi process in which the long double-stranded RNA has been cut up into short (~21 nucleotides) double-stranded RNA. The siRNA stimulates the cellular machinery to cut up other single-stranded RNA having the same sequence as the siRNA. molecules that engage a group of cellular proteins called RISC RISCRNA-Induced silencing complex, a protein siRNA complex that can recognize and destroy target mRNAs. (RNA induced silencing complex). The RISC guides the siRNA to its target messenger that is copied from a gene with the intention of being translated by ribosomes into a protein molecule. (mRNA mRNAmessenger RNA– the messenger between DNA DNADeoxyribonucleic acid. The primary genetic material of the cell, consisting of two long chains of nucleotides twisted together into a double helix. The sequence of the nucleotides (A, G, C, and T) in the DNA defines the genetic code for the organism; the sequence is copied and maintained through the complementary pairing of nucleotides (A with T, and G with C) across the strands of the double helix.and proteins) to destroy the mRNA. The process is extremely specific and enables siRNA to break up the mRNA associated with a disease-causing gene geneThe basic unit of genetic information, which is coded in the characteristic string of nucleotide bases (coded as A, C, T and G), in a specific sequence that provides the information usually for making a specific protein.or virus.
Okay so siRNA is a short piece of RNA that attaches itself to a RISC complex and directs the nucleic acid destroying enzyme to mRNA. The mRNA is chopped up and the protein doesn't get made. There are many questions regarding the actual mechanism of action. Does siRNA have to be double or single stranded? Is there any logic behind what fragment of the mRNA must be homologous with the siRNA? Does one piece of siRNA lead to many other pieces (after the mRNA is chopped up) which leads to more mRNA destruction? How does it end?
It is known that the effect is quite often short lived. The siRNA must be delivered into a cell which has lead to every researcher in the field testing various transfection reagents. The papers on delivery have yet to establish a coherent explanation of how this will work as a drug. Some targets are knocked down to a greater degree than others. The effect lasts longer in some targets than others. The RISC complex is made up of proteins. What happens if you try to knock out one of those proteins?
The entire field began back in 1989 when researchers were trying to make a purple petunia more purple by adding RNA that codes for purple. What they got was a white petunia. The color was eliminated and thus, they concluded that they knocked out the gene. Anti-sense had also been shown to knock out plant colors. The mechanism there is different. The entire anti-sense strand of an mRNA is attached to the mRNA molecule thus blocking it from being translated. (why wouldn't siRNA do this?) Later siRNA was shown to knock out genes in mammalian cells and the biotech world was off to the races. Money came in and careers and companies (like Ribozyme Pharmaceuticals) were revived. Papers on how RNAi works have chimed in on what the rules are for developing a good siRNA. The papers go into details of molecular modifications that make siRNA molecules more effective. Companies like
Qiagen, Invitrogen, Dharmacon and Sigma have all cashed in on the Biotech appetite for expensive little pieces of RNA and the assays needed to do the research.
Years later, there is no drug on the market. There is no definitive experiement that explains the mechanism. siRNA is going the way of gene therapry and anti-sense technology. Once again we've been fooled! Was it the marketing departments of Qiagen, Invitrogen, Dharmacon and Sigma? Were companies like Ribozyme Pharmaceuticals desparate for a new approach to RNA therapy? It seems as if we do not really know enough about the basics of nucliec acids inside a cell to really describe what is happening. We know that protein production is regulated. How, for example, is a protein downregulated? How does the cell know if it has enough protein? By the mRNA levels? Could this be effected by short pieces of the mRNA? What have we learned about the measurements of proteins and mRNA? Can we use RT PCR to acurately measure mRNA levels? The answer is no. Why not? Shouldn't RT PCR be corralated to protein levels? If not, what does that tell us about our understanding of the quantitation of nucleic acids and protein production?
There are so many questions left open for the scientific mind. Something is happening but what. Biotech companies are very simple in their approach to research. Whether they've chosen antibody technology, siRNA or some other small molecule approach, all they do is select a target and throw the technology at it. The details are left up to junior personel who don't stand a chance. It's too simple. The real science can only be done by those who don't care about the effects, but rather the measurements. Are they real and can they fit some mathematical model? The research could at least answer questions on the outside, such as how can we measure protein production? Tartrate resistant alkaline phosphatase for example is upregulated as osteoclast precursors fuse into an osteoclast. Prior to witnessing with your own eyes the final formation of the osteoclasts, the TRAP production stops. Can we find a way of predicting exactly when the production goes down. Do the enzyme activity measurements corrolate with enzyme production? How is the activity stopped? How is production shut down? So many questions and all basic and all fascinating if you think that the world inside of a cell is the great unknown.
Inside a cell there are little pockets of highly acidic solutions. There are scaffolds where RNA conducts the production of proteins. There are shuttles that take the proteins where they need to go. There is DNA twisting around making more DNA and RNA. There is a time when the whole production needs to focus on making another cell just like itself. To simply call up Invitrogen and order some siRNA against a target and have some kid mix it all up and run an assay and give you a PowerPoint slide show with some Excel charts does not constistute science. So far siRNA has given us jack squat and I predict that we will never see any real results from this latest trend. We may see a drug on the market but that doesn't count. Until we start studying our methods of measuring what happens inside a cell, we can't know what siRNA, or anti-sense is really doing. Even antibodies against proteins are a mystery. A recent paper on anti-TNF alpha showed that the antibody lead to an increase in protein production. Was the measurement accurate? Did the antibody cause more protein to be made because the protein interacting with the antibody was tied up? So many questions. They may be naive questions but those are usually the best ones. The big brained scientists sometimes get too fancy. The big funded scientists have gotten way to simple. The questions we attempt to answer should be simple. The answers may or may not be simple. That's the fun of trying to find things out. You never know how it will play out. What goes on in a cell? We just don't know yet.
There once was a Biotechnology company called Ribozyme Pharmaceuticals Inc. They failed. RNAi came along and they reinvented the company, "at the forefront of the effort to create RNAi-based therapies." They describe the technology as follows:
RNAi is a natural, selective process for turning off genes. RNAi is triggered by short interfering RNA (siRNA). An intermediate in the RNAi process in which the long double-stranded RNA has been cut up into short (~21 nucleotides) double-stranded RNA. The siRNA stimulates the cellular machinery to cut up other single-stranded RNA having the same sequence as the siRNA. molecules that engage a group of cellular proteins called RISC RISCRNA-Induced silencing complex, a protein siRNA complex that can recognize and destroy target mRNAs. (RNA induced silencing complex). The RISC guides the siRNA to its target messenger that is copied from a gene with the intention of being translated by ribosomes into a protein molecule. (mRNA mRNAmessenger RNA– the messenger between DNA DNADeoxyribonucleic acid. The primary genetic material of the cell, consisting of two long chains of nucleotides twisted together into a double helix. The sequence of the nucleotides (A, G, C, and T) in the DNA defines the genetic code for the organism; the sequence is copied and maintained through the complementary pairing of nucleotides (A with T, and G with C) across the strands of the double helix.and proteins) to destroy the mRNA. The process is extremely specific and enables siRNA to break up the mRNA associated with a disease-causing gene geneThe basic unit of genetic information, which is coded in the characteristic string of nucleotide bases (coded as A, C, T and G), in a specific sequence that provides the information usually for making a specific protein.or virus.
Okay so siRNA is a short piece of RNA that attaches itself to a RISC complex and directs the nucleic acid destroying enzyme to mRNA. The mRNA is chopped up and the protein doesn't get made. There are many questions regarding the actual mechanism of action. Does siRNA have to be double or single stranded? Is there any logic behind what fragment of the mRNA must be homologous with the siRNA? Does one piece of siRNA lead to many other pieces (after the mRNA is chopped up) which leads to more mRNA destruction? How does it end?
It is known that the effect is quite often short lived. The siRNA must be delivered into a cell which has lead to every researcher in the field testing various transfection reagents. The papers on delivery have yet to establish a coherent explanation of how this will work as a drug. Some targets are knocked down to a greater degree than others. The effect lasts longer in some targets than others. The RISC complex is made up of proteins. What happens if you try to knock out one of those proteins?
The entire field began back in 1989 when researchers were trying to make a purple petunia more purple by adding RNA that codes for purple. What they got was a white petunia. The color was eliminated and thus, they concluded that they knocked out the gene. Anti-sense had also been shown to knock out plant colors. The mechanism there is different. The entire anti-sense strand of an mRNA is attached to the mRNA molecule thus blocking it from being translated. (why wouldn't siRNA do this?) Later siRNA was shown to knock out genes in mammalian cells and the biotech world was off to the races. Money came in and careers and companies (like Ribozyme Pharmaceuticals) were revived. Papers on how RNAi works have chimed in on what the rules are for developing a good siRNA. The papers go into details of molecular modifications that make siRNA molecules more effective. Companies like
Qiagen, Invitrogen, Dharmacon and Sigma have all cashed in on the Biotech appetite for expensive little pieces of RNA and the assays needed to do the research.
Years later, there is no drug on the market. There is no definitive experiement that explains the mechanism. siRNA is going the way of gene therapry and anti-sense technology. Once again we've been fooled! Was it the marketing departments of Qiagen, Invitrogen, Dharmacon and Sigma? Were companies like Ribozyme Pharmaceuticals desparate for a new approach to RNA therapy? It seems as if we do not really know enough about the basics of nucliec acids inside a cell to really describe what is happening. We know that protein production is regulated. How, for example, is a protein downregulated? How does the cell know if it has enough protein? By the mRNA levels? Could this be effected by short pieces of the mRNA? What have we learned about the measurements of proteins and mRNA? Can we use RT PCR to acurately measure mRNA levels? The answer is no. Why not? Shouldn't RT PCR be corralated to protein levels? If not, what does that tell us about our understanding of the quantitation of nucleic acids and protein production?
There are so many questions left open for the scientific mind. Something is happening but what. Biotech companies are very simple in their approach to research. Whether they've chosen antibody technology, siRNA or some other small molecule approach, all they do is select a target and throw the technology at it. The details are left up to junior personel who don't stand a chance. It's too simple. The real science can only be done by those who don't care about the effects, but rather the measurements. Are they real and can they fit some mathematical model? The research could at least answer questions on the outside, such as how can we measure protein production? Tartrate resistant alkaline phosphatase for example is upregulated as osteoclast precursors fuse into an osteoclast. Prior to witnessing with your own eyes the final formation of the osteoclasts, the TRAP production stops. Can we find a way of predicting exactly when the production goes down. Do the enzyme activity measurements corrolate with enzyme production? How is the activity stopped? How is production shut down? So many questions and all basic and all fascinating if you think that the world inside of a cell is the great unknown.
Inside a cell there are little pockets of highly acidic solutions. There are scaffolds where RNA conducts the production of proteins. There are shuttles that take the proteins where they need to go. There is DNA twisting around making more DNA and RNA. There is a time when the whole production needs to focus on making another cell just like itself. To simply call up Invitrogen and order some siRNA against a target and have some kid mix it all up and run an assay and give you a PowerPoint slide show with some Excel charts does not constistute science. So far siRNA has given us jack squat and I predict that we will never see any real results from this latest trend. We may see a drug on the market but that doesn't count. Until we start studying our methods of measuring what happens inside a cell, we can't know what siRNA, or anti-sense is really doing. Even antibodies against proteins are a mystery. A recent paper on anti-TNF alpha showed that the antibody lead to an increase in protein production. Was the measurement accurate? Did the antibody cause more protein to be made because the protein interacting with the antibody was tied up? So many questions. They may be naive questions but those are usually the best ones. The big brained scientists sometimes get too fancy. The big funded scientists have gotten way to simple. The questions we attempt to answer should be simple. The answers may or may not be simple. That's the fun of trying to find things out. You never know how it will play out. What goes on in a cell? We just don't know yet.
Monday, May 08, 2006
What We Know but Cannot Prove is So
It's an interesting question. We know things deep in our hearts yet they are things we cannot prove. Many people believe in Gods. Their scoiety backs them up and eliminates the need for hard core proof. Others around them can choose not to believe but society will make the non-believer the outcast. There is no way of knowing how to prove the existance or non-existance of god. All one can do is use their beliefs to make sense of the world.
I believe something that I cannot prove. I believe that there are people among us who, given the opportunity, could be brilliant scientists. These people work as carpenters, bakers, ditch diggers, and all sorts of, what we believe, are lower forms of contributions to society. Given the chance they could figure out how life began on earth. They could help ease world poverty, hunger, war, and all of the other real problems that confound mankind.
One example is Kary Mullis, the man who dreamed up Polymerase Chain Reaction. This technology is used to amplify DNA. He won the Nobel prize for this work. He was considered a slacker by his superiors, even after they sold the technology for over 300 million dollars. Kary was given a ten thousand dollar bonus. Prior to this job, where he outlined how PCR would work, where his company made hundred of millions for this scientific idea, where the Nobel prize was earned, Kary worked as a baker. He baked bread and muffins and cakes.
Imagine, this mind working away in a bakery. The smell of fresh bread wafting through the air. Customers are picking up orders as casual is exchanged over the display cabinets. Somewhere else there is a biotechnology company starting up. They put together their business plan, seek out funding, write up the corporate policies and so on. At some point they probably picked up something from the bakery for an early morning meeting. One day the need for a supervisor is discussed at the biotech company. "We need someone who will supervise the DNA amplification group." In the old days DNA was amplified by growing it in viruses. Kary decides he needs more money so he leaves and joins the new biotech company. A few years later, after all the meetings and the original research plans have been forgotten, the company cashes in on the one idea from the ex-baker.
Somewhere out there, right now, a group of attractive and well dressed individuals are sitting in a board room overlooking New York City. Among this group are lawyers, MBAs, PhDs from the finest schools. They are making a plans that will make them rich. Somewhere else there is a young girl, gutting fish in a factory off the shores of the Mississippi. Given the chance she has the kind of brain that could turn water into fuel. She'll never figure out how to earn a decent living however.
I use this belief to make sense of the world. If our leaders were truly the best at what they do then we'd live in a perfect world. Most likely, the truth is that our leaders are the best at getting themselves promoted. Our leaders know what society believes and treat the beliefs as if they were truths. If you want to be president in America, you have to go to church. You must believe in God. Likewise, if you want to be a successful scientist you must believe in the current dogma of the establishment. If you want to be involved in discovery, you have to know what the current trends in popular thought are, and you have to start tearing them down. Piece by piece you have to get to the heart of the matter and see if "the truth" really is the truth.
There are probably only a handful of individuals who have the ability to get at the truth. There are certainly far more individuals who can learn something in a book and pass that information on as if they understand it. The young lady working at the fish factory in Mississippi might read something in a book that is short on logic and thus she appears confused. Teachers will misconstrue this as not understanding. The truth is that the teacher doesn't understand that what was written was not acceptable to the type of person who has the ability to get at the truth.
Galaleo once told the church that the world revolved around the sun. They threw him in jail. He didn't understand that the world revolved around us because God made us and we were the center of the universe. Galaleo looked up at the stars and asked them what they thought. Real learning is not done in a book. It is done by looking at the world around you and trying to come up with explanations for the way things are. Why do fish live in water and humans on land? I can imagine the young lady in Mississippi thinking these thoughts as she's gutting fish on the second shift. The sun is slanting through the dirty windows of the factory in the late Mississippi evening. The shift boss and the other workers are focused on their gutting techniques or maybe what they are going to do at midnight when they are off. The young lady has her thoughts and never thinks about what to do with them. She was never taught self promotion and it never occured to her. She can think about the natural world but the human world is too hard.
I can't prove that she exists. I think she does and she knows why fish survive in water.
I believe something that I cannot prove. I believe that there are people among us who, given the opportunity, could be brilliant scientists. These people work as carpenters, bakers, ditch diggers, and all sorts of, what we believe, are lower forms of contributions to society. Given the chance they could figure out how life began on earth. They could help ease world poverty, hunger, war, and all of the other real problems that confound mankind.
One example is Kary Mullis, the man who dreamed up Polymerase Chain Reaction. This technology is used to amplify DNA. He won the Nobel prize for this work. He was considered a slacker by his superiors, even after they sold the technology for over 300 million dollars. Kary was given a ten thousand dollar bonus. Prior to this job, where he outlined how PCR would work, where his company made hundred of millions for this scientific idea, where the Nobel prize was earned, Kary worked as a baker. He baked bread and muffins and cakes.
Imagine, this mind working away in a bakery. The smell of fresh bread wafting through the air. Customers are picking up orders as casual is exchanged over the display cabinets. Somewhere else there is a biotechnology company starting up. They put together their business plan, seek out funding, write up the corporate policies and so on. At some point they probably picked up something from the bakery for an early morning meeting. One day the need for a supervisor is discussed at the biotech company. "We need someone who will supervise the DNA amplification group." In the old days DNA was amplified by growing it in viruses. Kary decides he needs more money so he leaves and joins the new biotech company. A few years later, after all the meetings and the original research plans have been forgotten, the company cashes in on the one idea from the ex-baker.
Somewhere out there, right now, a group of attractive and well dressed individuals are sitting in a board room overlooking New York City. Among this group are lawyers, MBAs, PhDs from the finest schools. They are making a plans that will make them rich. Somewhere else there is a young girl, gutting fish in a factory off the shores of the Mississippi. Given the chance she has the kind of brain that could turn water into fuel. She'll never figure out how to earn a decent living however.
I use this belief to make sense of the world. If our leaders were truly the best at what they do then we'd live in a perfect world. Most likely, the truth is that our leaders are the best at getting themselves promoted. Our leaders know what society believes and treat the beliefs as if they were truths. If you want to be president in America, you have to go to church. You must believe in God. Likewise, if you want to be a successful scientist you must believe in the current dogma of the establishment. If you want to be involved in discovery, you have to know what the current trends in popular thought are, and you have to start tearing them down. Piece by piece you have to get to the heart of the matter and see if "the truth" really is the truth.
There are probably only a handful of individuals who have the ability to get at the truth. There are certainly far more individuals who can learn something in a book and pass that information on as if they understand it. The young lady working at the fish factory in Mississippi might read something in a book that is short on logic and thus she appears confused. Teachers will misconstrue this as not understanding. The truth is that the teacher doesn't understand that what was written was not acceptable to the type of person who has the ability to get at the truth.
Galaleo once told the church that the world revolved around the sun. They threw him in jail. He didn't understand that the world revolved around us because God made us and we were the center of the universe. Galaleo looked up at the stars and asked them what they thought. Real learning is not done in a book. It is done by looking at the world around you and trying to come up with explanations for the way things are. Why do fish live in water and humans on land? I can imagine the young lady in Mississippi thinking these thoughts as she's gutting fish on the second shift. The sun is slanting through the dirty windows of the factory in the late Mississippi evening. The shift boss and the other workers are focused on their gutting techniques or maybe what they are going to do at midnight when they are off. The young lady has her thoughts and never thinks about what to do with them. She was never taught self promotion and it never occured to her. She can think about the natural world but the human world is too hard.
I can't prove that she exists. I think she does and she knows why fish survive in water.
Thursday, May 04, 2006
Brother Can You Spare a Dime
Medical bioethicist Leigh Turner of McGill University, Quebec
"Biotech, in a similar manner to many religious movements, has its charismatic prophets, enthusiastic evangelists and enrapt audiences. Like religions, it offers a comforting message of salvation. Instead of imagining a day of rapture when the dead rise from their graves to begin eternal life, biotech enthusiasts imagine the era when medical technologies provide a renewable, largely imperishable body. … Biotech is not just an assemblage of research programs and techniques. In a scientific and technological era, biotech also offers a surrogate religious framework for many individuals."
Biotechnology research is mostly cargo cult science. The actual research is performed by some of the lowest paid individuals in a company. The data is hand selected for presentation so as to not offend the corporate ideology. It is then filtered through executives to the investing community. The purpose of this process is to extract money from investors who are easily swayed by the charismatic prophets.
After attending the BIO 2004 conference reporter David Ewing wrote in the San Francisco Chronicle, "As of yet, most of what I’m looking for here is in the ‘promise’ category - and has been each year I have come to this ever-larger industry fete."
"Last year, this industry lost $5.4 billion, and has lost a staggering $57.7 billion since BIO last held its annual conference in San Francisco in 1994, according to an Ernst and Young study. Only a few companies have been consistently profitable in the 30 years since biotech was born - a few, such as Amgen and Genentech, fantastically so. Remove them, and the losses and numbers are far worse for the rest of the industry."
Biotechnology simply has not succeeded in applying real science to develop products. It has succeeded only in selling stocks. According to Burrill & Co., US biotech firms raised almost $4 billion by selling new stock to investors in 2004. US biotechs posted almost that much in losses the same year. That is not the power of science. That is the power of greed over common sense. How can the recent discoveries in basic molecular biology and 100 billion dollars lead to jack squat?
Let us go back to Richard Feynmans Cargo Cult Science.
"I began to think, what else is there that we believe? (And I thought then about the witch doctors, and how easy it would have been to check on them by noticing that nothing really worked.) So I found things that even more people believe, such as that we have some knowledge of how to educate. There are big schools of reading methods and mathematics methods, and so forth, but if you notice, you'll see the reading scores keep going down--or hardly going up--in spite of the fact that we continually use these same people to improve the methods. There's a witch doctor remedy that doesn't work. It ought to be looked into; how do they know that their method should work? Another example is how to treat criminals. We obviously have made no progress--lots of theory, but no progress--in decreasing the amount of crime by the method that we use to handle criminals.
Yet these things are said to be scientific. We study them. And I think ordinary people with commonsense ideas are intimidated by this pseudoscience. A teacher who has some good idea of how to teach her children to read is forced by the school system to do it some other way--or is even fooled by the school system into thinking that her method is not necessarily a good one. Or a parent of bad boys, after disciplining them in one way or another, feels guilty for the rest of her life because she didn't do "the right thing," according to the experts.
So we really ought to look into theories that don't work, and science that isn't science."
Why don't we look into the biotech theories that don't work? How's that genome project working out for us? What about the promise of gene therapy and now siRNA therapy? There are so many examples of Cargo Cult Science in the history and present day biotechnology that it could become a field all its own. At least it could become an important part of the philosophy of science. There are things to be learned in failed experiements. As such, there is a whole lot to be learned from Biotechnology. Mostly we could learn about human nature. What makes a large group of well funded, well educated men and women sit around and try to sell the world a drug like Vioxx? Why do people take monoclonal antibodies against TNF alpha when it has been shown to not only have little effect, but it has also been shown to increase levels of TNF alpha! An entire book needs to be devoted to the story of statins and cholesterol levels.
No one can say what is missing better than Feynman.
"But there is one feature I notice that is generally missing in cargo cult science. That is the idea that we all hope you have learned in studying science in school--we never say explicitly what this is, but just hope that you catch on by all the examples of scientific investigation. It is interesting, therefore, to bring it out now and speak of it explicitly. It's a kind of scientific integrity, a principle of scientific thought that corresponds to a kind of utter honesty--a kind of leaning over backwards. For example, if you're doing an experiment, you should report everything that you think might make it invalid--not only what you think is right about it: other causes that could possibly explain your results; and things you thought of that you've eliminated by some other experiment, and how they worked--to make sure the other fellow can tell they have been eliminated. "
Investors quite often do not have the scientific background to make good decisions when dealing with the charismatic prophets of biotechnology. It's nothing to be embarrassed about. Every venture capital group needs to fund a small laboratory. The scientific staff of that laboratory needs to reproduce key experiments and read the scientific literature very carefully. They must bend over backwards to prove it wrong. If they can't, then it might just be a good investment.
"Biotech, in a similar manner to many religious movements, has its charismatic prophets, enthusiastic evangelists and enrapt audiences. Like religions, it offers a comforting message of salvation. Instead of imagining a day of rapture when the dead rise from their graves to begin eternal life, biotech enthusiasts imagine the era when medical technologies provide a renewable, largely imperishable body. … Biotech is not just an assemblage of research programs and techniques. In a scientific and technological era, biotech also offers a surrogate religious framework for many individuals."
Biotechnology research is mostly cargo cult science. The actual research is performed by some of the lowest paid individuals in a company. The data is hand selected for presentation so as to not offend the corporate ideology. It is then filtered through executives to the investing community. The purpose of this process is to extract money from investors who are easily swayed by the charismatic prophets.
After attending the BIO 2004 conference reporter David Ewing wrote in the San Francisco Chronicle, "As of yet, most of what I’m looking for here is in the ‘promise’ category - and has been each year I have come to this ever-larger industry fete."
"Last year, this industry lost $5.4 billion, and has lost a staggering $57.7 billion since BIO last held its annual conference in San Francisco in 1994, according to an Ernst and Young study. Only a few companies have been consistently profitable in the 30 years since biotech was born - a few, such as Amgen and Genentech, fantastically so. Remove them, and the losses and numbers are far worse for the rest of the industry."
Biotechnology simply has not succeeded in applying real science to develop products. It has succeeded only in selling stocks. According to Burrill & Co., US biotech firms raised almost $4 billion by selling new stock to investors in 2004. US biotechs posted almost that much in losses the same year. That is not the power of science. That is the power of greed over common sense. How can the recent discoveries in basic molecular biology and 100 billion dollars lead to jack squat?
Let us go back to Richard Feynmans Cargo Cult Science.
"I began to think, what else is there that we believe? (And I thought then about the witch doctors, and how easy it would have been to check on them by noticing that nothing really worked.) So I found things that even more people believe, such as that we have some knowledge of how to educate. There are big schools of reading methods and mathematics methods, and so forth, but if you notice, you'll see the reading scores keep going down--or hardly going up--in spite of the fact that we continually use these same people to improve the methods. There's a witch doctor remedy that doesn't work. It ought to be looked into; how do they know that their method should work? Another example is how to treat criminals. We obviously have made no progress--lots of theory, but no progress--in decreasing the amount of crime by the method that we use to handle criminals.
Yet these things are said to be scientific. We study them. And I think ordinary people with commonsense ideas are intimidated by this pseudoscience. A teacher who has some good idea of how to teach her children to read is forced by the school system to do it some other way--or is even fooled by the school system into thinking that her method is not necessarily a good one. Or a parent of bad boys, after disciplining them in one way or another, feels guilty for the rest of her life because she didn't do "the right thing," according to the experts.
So we really ought to look into theories that don't work, and science that isn't science."
Why don't we look into the biotech theories that don't work? How's that genome project working out for us? What about the promise of gene therapy and now siRNA therapy? There are so many examples of Cargo Cult Science in the history and present day biotechnology that it could become a field all its own. At least it could become an important part of the philosophy of science. There are things to be learned in failed experiements. As such, there is a whole lot to be learned from Biotechnology. Mostly we could learn about human nature. What makes a large group of well funded, well educated men and women sit around and try to sell the world a drug like Vioxx? Why do people take monoclonal antibodies against TNF alpha when it has been shown to not only have little effect, but it has also been shown to increase levels of TNF alpha! An entire book needs to be devoted to the story of statins and cholesterol levels.
No one can say what is missing better than Feynman.
"But there is one feature I notice that is generally missing in cargo cult science. That is the idea that we all hope you have learned in studying science in school--we never say explicitly what this is, but just hope that you catch on by all the examples of scientific investigation. It is interesting, therefore, to bring it out now and speak of it explicitly. It's a kind of scientific integrity, a principle of scientific thought that corresponds to a kind of utter honesty--a kind of leaning over backwards. For example, if you're doing an experiment, you should report everything that you think might make it invalid--not only what you think is right about it: other causes that could possibly explain your results; and things you thought of that you've eliminated by some other experiment, and how they worked--to make sure the other fellow can tell they have been eliminated. "
Investors quite often do not have the scientific background to make good decisions when dealing with the charismatic prophets of biotechnology. It's nothing to be embarrassed about. Every venture capital group needs to fund a small laboratory. The scientific staff of that laboratory needs to reproduce key experiments and read the scientific literature very carefully. They must bend over backwards to prove it wrong. If they can't, then it might just be a good investment.
Tuesday, May 02, 2006
What Happened Here?
Drug makers are in a tough business. Here are a few companies and their failures.
DOV Pharmaceutical: ...DOV Pharmaceutical, Inc. (NASDAQ: DOVP) announced today high-level results recently developed from the first Phase III placebo-controlled clinical trial – study 020 – of its novel analgesic bicifadine in patients with chronic low back pain (CLBP). Bicifadine did not achieve a statistically significant effect relative to placebo on the primary endpoint of the study at any of the doses tested:
Nastech Pharmaceutical: ...Merck & Co. ended its collaboration with Nastech Pharmaceutical Co. on a spray treatment for obesity because the product wasn't effective in early studies.
CancerVax: ...Another round of disappointing clinical trial data has led CancerVax and Serono to abandon research on a treatment for malignant melanoma
Cell Therapeutics: ...said a late-stage clinical trial of its Xyotax treatment for non-small cell lung cancer didn't go well, falling short of its primary goal of showing that Xyotax works better than standard chemotherapy.
Targeted Genetics: ...said its experimental cystic fibrosis treatment failed to significantly improve lung function in clinical-trial patients over those who received placebo
NeoRx: ...The Skeletal Targeted Radiotherapy program has a long history of ups and downs, and the company has burned through millions of dollars in its development. The FDA suspended clinical trials of the therapy in October 2000 after several patients developed serious delayed side effects.
You get the point...
But what about this one?
TeGenero: ...six test subjects were hospitalized for several weeks after severe reactions to injections of the TeGenero medicine at a Parexel facility in north London on March 13. Five of the volunteers have since been released. The sixth may have to stay in the hospital for as long as six months, and is certain to lose the tips of three fingers
The first set of failures showed a lack of efficacy. The latter was highy effective but in a negative way. The latter drug was an antibody. There are currently 18 antibody drugs on the market. The one thing you can say about the antibody drugs is that they have an effect. I have personally used Rituxan in tumor studies using mice and that drug completely eliminated tumors in mice. I have no comments on their effects in human beings. The point is that some "drugs" make you well, some make you ill, and the ones that most pharmaceutical companies sell you don't do anything at all.
The Cargo Cult scenario: Many rituals were performed but no airplanes came. Someone found a radio and a book on the Japanese language. They put together some very offensive words and spoke them into the radio. They also gave their location. Planes came but they dropped bombs instead of cargo. What the cargo needs to do here is to find out how to apologize in Japanese and ask politely for cargo. At least with the hostile reaction, the cargo cult got something. When nothing happens they continue down the same path that leads to nothing.
DOV Pharmaceutical: ...DOV Pharmaceutical, Inc. (NASDAQ: DOVP) announced today high-level results recently developed from the first Phase III placebo-controlled clinical trial – study 020 – of its novel analgesic bicifadine in patients with chronic low back pain (CLBP). Bicifadine did not achieve a statistically significant effect relative to placebo on the primary endpoint of the study at any of the doses tested:
Nastech Pharmaceutical: ...Merck & Co. ended its collaboration with Nastech Pharmaceutical Co. on a spray treatment for obesity because the product wasn't effective in early studies.
CancerVax: ...Another round of disappointing clinical trial data has led CancerVax and Serono to abandon research on a treatment for malignant melanoma
Cell Therapeutics: ...said a late-stage clinical trial of its Xyotax treatment for non-small cell lung cancer didn't go well, falling short of its primary goal of showing that Xyotax works better than standard chemotherapy.
Targeted Genetics: ...said its experimental cystic fibrosis treatment failed to significantly improve lung function in clinical-trial patients over those who received placebo
NeoRx: ...The Skeletal Targeted Radiotherapy program has a long history of ups and downs, and the company has burned through millions of dollars in its development. The FDA suspended clinical trials of the therapy in October 2000 after several patients developed serious delayed side effects.
You get the point...
But what about this one?
TeGenero: ...six test subjects were hospitalized for several weeks after severe reactions to injections of the TeGenero medicine at a Parexel facility in north London on March 13. Five of the volunteers have since been released. The sixth may have to stay in the hospital for as long as six months, and is certain to lose the tips of three fingers
The first set of failures showed a lack of efficacy. The latter was highy effective but in a negative way. The latter drug was an antibody. There are currently 18 antibody drugs on the market. The one thing you can say about the antibody drugs is that they have an effect. I have personally used Rituxan in tumor studies using mice and that drug completely eliminated tumors in mice. I have no comments on their effects in human beings. The point is that some "drugs" make you well, some make you ill, and the ones that most pharmaceutical companies sell you don't do anything at all.
The Cargo Cult scenario: Many rituals were performed but no airplanes came. Someone found a radio and a book on the Japanese language. They put together some very offensive words and spoke them into the radio. They also gave their location. Planes came but they dropped bombs instead of cargo. What the cargo needs to do here is to find out how to apologize in Japanese and ask politely for cargo. At least with the hostile reaction, the cargo cult got something. When nothing happens they continue down the same path that leads to nothing.
Wednesday, February 08, 2006
Two Cargo Cult Crews Cut
Two local Seattle biotech companies recently let go a substantial percentage of their staff. Dendreon released 34 employees equalling 15%. Targeted Genetics let go of 26 equalling 27%.
Dendreon: "Many of those employees worked on early-stage research projects. "
Targeted Genetics: "The employees worked on early-stage research projects and in operations and administration. "
Early stage R & D! They spend a lot of money and quite often end up with little to show for it. Both of the above companies are saving their resources to fund bigger projects that are further along the research path. Both companies thus have products that survived the early-stage R&D process and gave everyone a reason to focus their investments in advancing the drugs to the market. That means the early-stage people need to pack their bags and find another group of researchers in need of their talents. The research that they did will be put on a back burner and who knows, maybe it'll be given a second chance someday. For now, the strong has survived and the weak has been sent packing.
The cargo cult medical science business requires people to wear white lab coats. They conduct "research" that leads to products that are sold to people who need help with some physical condition. It is expensive which leads to most projects being cut prior to reaching the clinical trial stage. In spite of the selectivity in basic research, most clinical trials fail. One has to ask, who is making the decision on what research goes forward? How much science is involved and how does the business model influence the science.
One quick example of a popular business model in the pharmaceutical world here. Treating rhumatoid arthritis is a huge market in America. One way of treating rhumatoid arthritis is to find molecules that bind to TNF alpha. TNF alpha blockers on the market bring in billions of dollars every year. That has the rest of the industry scrambling to hire white lab coat scientists to look for TNF alpha binders. If something binds it must then be shown to "treat" rhumatoid arthritis. At this stage the clinical trial people can take over and the science becomes much different. Results can be dealt with. Making it to that stage however is not easy. You have to convince the executives that you have a molecule that can work as a drug. You have to prove that it binds to its target and disrupts the targets normal function. Once you've succeeded, you're work is done. Literally, you're set to go... away. You're damned if you do and your damned if you don't.
Dendreon and Targeted Genetics crews fell into the damned if you don't category. They are going away due to a lack of progress. You have to tell yourself that it wasn't you that was rejected, it was the original idea that failed to impress. You did not come up with the idea. You still have to go but you did your best. It's the cargo cult that is not bringing the airplanes. You are merely sitting in the watch tower with the coconuts over your ears, waiting for the planes to land.
Dendreon: "Many of those employees worked on early-stage research projects. "
Targeted Genetics: "The employees worked on early-stage research projects and in operations and administration. "
Early stage R & D! They spend a lot of money and quite often end up with little to show for it. Both of the above companies are saving their resources to fund bigger projects that are further along the research path. Both companies thus have products that survived the early-stage R&D process and gave everyone a reason to focus their investments in advancing the drugs to the market. That means the early-stage people need to pack their bags and find another group of researchers in need of their talents. The research that they did will be put on a back burner and who knows, maybe it'll be given a second chance someday. For now, the strong has survived and the weak has been sent packing.
The cargo cult medical science business requires people to wear white lab coats. They conduct "research" that leads to products that are sold to people who need help with some physical condition. It is expensive which leads to most projects being cut prior to reaching the clinical trial stage. In spite of the selectivity in basic research, most clinical trials fail. One has to ask, who is making the decision on what research goes forward? How much science is involved and how does the business model influence the science.
One quick example of a popular business model in the pharmaceutical world here. Treating rhumatoid arthritis is a huge market in America. One way of treating rhumatoid arthritis is to find molecules that bind to TNF alpha. TNF alpha blockers on the market bring in billions of dollars every year. That has the rest of the industry scrambling to hire white lab coat scientists to look for TNF alpha binders. If something binds it must then be shown to "treat" rhumatoid arthritis. At this stage the clinical trial people can take over and the science becomes much different. Results can be dealt with. Making it to that stage however is not easy. You have to convince the executives that you have a molecule that can work as a drug. You have to prove that it binds to its target and disrupts the targets normal function. Once you've succeeded, you're work is done. Literally, you're set to go... away. You're damned if you do and your damned if you don't.
Dendreon and Targeted Genetics crews fell into the damned if you don't category. They are going away due to a lack of progress. You have to tell yourself that it wasn't you that was rejected, it was the original idea that failed to impress. You did not come up with the idea. You still have to go but you did your best. It's the cargo cult that is not bringing the airplanes. You are merely sitting in the watch tower with the coconuts over your ears, waiting for the planes to land.
Wednesday, January 25, 2006
That flu vaccine finally arrives
That flu vaccine finally arrives...
Jan. 18 (HealthDay News)
"The two drugs -- both members of the neuraminidase inhibitor class of antivirals -- appear to be ineffective against seasonal flu outbreaks and should only be used in the event of a serious epidemic or pandemic, the study authors report in the Jan. 19 online edition of The Lancet."
"Roche fundamentally disagrees with the conclusions reached by the authors that Tamiflu should not be used for the treatment of prevention of seasonal influenza," said company spokesman Terry Hurley. "The conclusion is at odds with the opinion of experts and regulatory authorities around the world."
Appealing to the authority of man may not be a good idea when facing an influenza pandemic. The experts and regulatory authorities disagree with a study that found that they may have been wrong. Of course the experts are going to turn around and accuse the new study as being the one that is wrong. What matters however is the ability to help a large population fight off the influenza virus. What is at stake? The influenza pandemic of 1918-1919 killed more people than World War I, somewhere between 20 and 40 million people. I'm sure we all feel better knowing that there is a "vaccine" available but shouldn't we be concerned that the one we are choosing to use may not work? What if we were Marines in Iraq and someone told us that our guns may not work. Would we not go out and fire our guns to check out the theory? Or would we call a meeting, assess the credentials of the two opposing authorities and decide whether or not to go into battle based upon who is more believable? Like a gun battle, this fight against the influenza virus might just be a life and death issue. It should be taken seriously. We should find out who is right and who is wrong.
So to sum up this cargo cult science; A long time ago some scientists in white lab coats developed a vaccine against the polio virus. They put an end (almost) to a horrible epidemic that killed thousands of young children. Now we have another virus that threatens to kill thousands. We have a vaccine. It was developed by people in white lab coats. Let the flu season begin.
Jan. 18 (HealthDay News)
"The two drugs -- both members of the neuraminidase inhibitor class of antivirals -- appear to be ineffective against seasonal flu outbreaks and should only be used in the event of a serious epidemic or pandemic, the study authors report in the Jan. 19 online edition of The Lancet."
"Roche fundamentally disagrees with the conclusions reached by the authors that Tamiflu should not be used for the treatment of prevention of seasonal influenza," said company spokesman Terry Hurley. "The conclusion is at odds with the opinion of experts and regulatory authorities around the world."
Appealing to the authority of man may not be a good idea when facing an influenza pandemic. The experts and regulatory authorities disagree with a study that found that they may have been wrong. Of course the experts are going to turn around and accuse the new study as being the one that is wrong. What matters however is the ability to help a large population fight off the influenza virus. What is at stake? The influenza pandemic of 1918-1919 killed more people than World War I, somewhere between 20 and 40 million people. I'm sure we all feel better knowing that there is a "vaccine" available but shouldn't we be concerned that the one we are choosing to use may not work? What if we were Marines in Iraq and someone told us that our guns may not work. Would we not go out and fire our guns to check out the theory? Or would we call a meeting, assess the credentials of the two opposing authorities and decide whether or not to go into battle based upon who is more believable? Like a gun battle, this fight against the influenza virus might just be a life and death issue. It should be taken seriously. We should find out who is right and who is wrong.
So to sum up this cargo cult science; A long time ago some scientists in white lab coats developed a vaccine against the polio virus. They put an end (almost) to a horrible epidemic that killed thousands of young children. Now we have another virus that threatens to kill thousands. We have a vaccine. It was developed by people in white lab coats. Let the flu season begin.
Tuesday, January 24, 2006
cargo cult scientist
cargo cult scientist
Two cargo cult "theories" came to a conclusive end this week. First the influenza vaccine, Tamiflu, was shown to have no effect over preventing the flu. Since vaccines are meant to prevent disease, this would be a failure. Tamiflu is being mass produced and stored away by the millions of doses in hopes of fighting what some believe will be very dangerous flu season. So let's sum this up; we have scientists in white lab coats producing a "vaccine" against a potentially deadly virus. We have governments buying up the product and storing it away in hospitals and pharmacies. Doctors are being educated by the manufacturers and government agencies as to how to administer the vaccine. People are becoming frightened by the media coverage of the flu virus prospects, yet resting assured that there is a vaccine that they can take. The vaccine will not help. Might as well rely on prayer.The second study was done with the HIV drugs. The idea was that by giving the drugs only when T cells reached a certain lower level, a more effective, or at least equally effective result could be achieved. Instead, people who took the drugs when their T cells got low, did considerably worse than people who took the drug on a daily basis. The clinical trial was halted due to the damage it was causing patients.This is Bullshitian medicine at it's finest. Previously a group of about ten patients seemed to get better by taking the reduced drug regime. But did the cargo cult scientists take into account all of the factors? Most importantly, does it make sense to give drugs that weaken the body to people who have dangerously low T cell counts? I say no it does not. The elite in the medical science business said yes it does. How many died?
Two cargo cult "theories" came to a conclusive end this week. First the influenza vaccine, Tamiflu, was shown to have no effect over preventing the flu. Since vaccines are meant to prevent disease, this would be a failure. Tamiflu is being mass produced and stored away by the millions of doses in hopes of fighting what some believe will be very dangerous flu season. So let's sum this up; we have scientists in white lab coats producing a "vaccine" against a potentially deadly virus. We have governments buying up the product and storing it away in hospitals and pharmacies. Doctors are being educated by the manufacturers and government agencies as to how to administer the vaccine. People are becoming frightened by the media coverage of the flu virus prospects, yet resting assured that there is a vaccine that they can take. The vaccine will not help. Might as well rely on prayer.The second study was done with the HIV drugs. The idea was that by giving the drugs only when T cells reached a certain lower level, a more effective, or at least equally effective result could be achieved. Instead, people who took the drugs when their T cells got low, did considerably worse than people who took the drug on a daily basis. The clinical trial was halted due to the damage it was causing patients.This is Bullshitian medicine at it's finest. Previously a group of about ten patients seemed to get better by taking the reduced drug regime. But did the cargo cult scientists take into account all of the factors? Most importantly, does it make sense to give drugs that weaken the body to people who have dangerously low T cell counts? I say no it does not. The elite in the medical science business said yes it does. How many died?
Thursday, January 05, 2006
Dr. Hwang Woo-suk Cargo Cult Top Scientist
Richard Feynman first described the Cargo Cult Science in an address to the graduating class of 1974.
"I think the educational and psychological studies I mentioned are examples of what I would like to call cargo cult science. In the South Seas there is a cargo cult of people. During the war they saw airplanes with lots of good materials, and they want the same thing to happen now. So they've arranged to make things like runways, to put fires along the sides of the runways, to make a wooden hut for a man to sit in, with two wooden pieces on his head to headphones and bars of bamboo sticking out like antennas--he's the controller--and they wait for the airplanes to land. 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. So I call these things cargo cult science, because they follow all the apparent precepts and forms of scientific investigation, but they're missing something essential, because the planes don't land."
Dr. Feynman was describing educational and psychological studies. I would like to create the Cargo Cult world right here in the form of a blog. All human endeavors have Cargo Cult people who "follow all the apparent precepts and forms". How many people have bosses who could never actaully do the work they supervise? They look at the work like the Cargo Cult leaders look at their airport. You can imagine the Cargo Cult setting up an HR department and hiring people to work in the airport. What qualifications would be needed? How would evals and promotions work?
Our order of business now is to establish the name of our cult. If we are going to create this cult it must have a name. As we progress we will add citizens to the tribe who represent the true spirit of the cargo cult.
The name of the cult (or tribe) will be... The Bullshitians
The Bullshitians have more than an airport. They are teachers, scientists, doctors, lawyers, construction workers and any other type of person who has ever existsted. They are real people in this world who rise to prominence. Our first citizen for example, is Dr. Hang Woo-suk. Dr. suk (for short) claimed to have made stem cells that contained the DNA of someone other than the person who produced the stem cell. That would be a stem cell clone my friends. The problem was that the clones were produced via some creative writing. There were no actual stem cells clones in existance. So somewhere, Dr. suk had people who wore white lab coats. These "scieentists" conducted experiments that were intended to bring clones into their world. The cells never actually showed up.
Of course the Bullshitians (my blog tribe) are real people who have to have real careers. They are not interested in whether or not the planes land and bring valuable cargo. It would be nice, but it's not necessary. Dr. suk represents our philosophy like no other. He was huge in the cloning business. He was South Koreas top scientist and he probably never cloned a damned thing. Good work I say. Dr. suk The Bullshitians top scientist!
P.S. We do require some form of evidence that the guy is full of shit. Like an ex-lover who is being served with a paternity suit, we would like to see a DNA test. Not from the mother who is sueing! When this comes in we will discuss it. We are interested in the planes landing but we are also interested in those that do not.
"I think the educational and psychological studies I mentioned are examples of what I would like to call cargo cult science. In the South Seas there is a cargo cult of people. During the war they saw airplanes with lots of good materials, and they want the same thing to happen now. So they've arranged to make things like runways, to put fires along the sides of the runways, to make a wooden hut for a man to sit in, with two wooden pieces on his head to headphones and bars of bamboo sticking out like antennas--he's the controller--and they wait for the airplanes to land. 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. So I call these things cargo cult science, because they follow all the apparent precepts and forms of scientific investigation, but they're missing something essential, because the planes don't land."
Dr. Feynman was describing educational and psychological studies. I would like to create the Cargo Cult world right here in the form of a blog. All human endeavors have Cargo Cult people who "follow all the apparent precepts and forms". How many people have bosses who could never actaully do the work they supervise? They look at the work like the Cargo Cult leaders look at their airport. You can imagine the Cargo Cult setting up an HR department and hiring people to work in the airport. What qualifications would be needed? How would evals and promotions work?
Our order of business now is to establish the name of our cult. If we are going to create this cult it must have a name. As we progress we will add citizens to the tribe who represent the true spirit of the cargo cult.
The name of the cult (or tribe) will be... The Bullshitians
The Bullshitians have more than an airport. They are teachers, scientists, doctors, lawyers, construction workers and any other type of person who has ever existsted. They are real people in this world who rise to prominence. Our first citizen for example, is Dr. Hang Woo-suk. Dr. suk (for short) claimed to have made stem cells that contained the DNA of someone other than the person who produced the stem cell. That would be a stem cell clone my friends. The problem was that the clones were produced via some creative writing. There were no actual stem cells clones in existance. So somewhere, Dr. suk had people who wore white lab coats. These "scieentists" conducted experiments that were intended to bring clones into their world. The cells never actually showed up.
Of course the Bullshitians (my blog tribe) are real people who have to have real careers. They are not interested in whether or not the planes land and bring valuable cargo. It would be nice, but it's not necessary. Dr. suk represents our philosophy like no other. He was huge in the cloning business. He was South Koreas top scientist and he probably never cloned a damned thing. Good work I say. Dr. suk The Bullshitians top scientist!
P.S. We do require some form of evidence that the guy is full of shit. Like an ex-lover who is being served with a paternity suit, we would like to see a DNA test. Not from the mother who is sueing! When this comes in we will discuss it. We are interested in the planes landing but we are also interested in those that do not.
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