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Thursday, May 30, 2013

Niaspan and Chinese IL-6

Right understanding is the most equally divided thing in the world, for everyone believes himself so well stored with it, that even those who in all other things are the hardest to be pleased, seldom desire more of it than they have. Wherein it is not likely that all men are deceived, but rather witness, that the faculty of right-judging and distinguishing truth from falsehood (which is properly called understanding or reasoning) is naturally equal in all men. And as the diversity of our opinions is not, because some are more reasonable than others, but only that we direct our thoughts several ways, neither do we consider the same things. For it is not enough to have good faculties, but the principal is to apply them well. Those who move but very slowly may advance much farther if they always follow the right way.  
Rene Descartes, A Discourse of a Method for the Well Guiding of Reason and Discovery
The "right-judging and distinguishing truth from falsehood" is a curious thing in modern medicine. AbbVie recently got some bad news regarding their "good cholesterol" drug, Niaspan. Two studies involving almost 30,000 people showed that the drug offered no benefit. The first study was halted after the NIH said patients on the medicine had strokes at double the rate of those just taking a companion drug. What did AbbVie do about this? They raised the cost of the pill 37%. What did the FDA do? Nothing.

We can't expect much from the FDA nor the companies who need their approval. The former is poorly structured, lazy and incompetent. The latter is forced to report only the positive news and hide the bad. The non-living entity that is The Corporation must be fed! It is up to great philosophers, such as Descartes and myself, to discuss "right judging and distinguishing truth from falsehood" in these matters. It is no easy task however, to begin to look into the realities of cholesterol medication and the single cause/cures of what ails the modern westerner. Gary Taubes, in Good Cholesterol Bad Cholesterol, dove into the history of the basic cholesterol research. If you believed the facts presented in this book to be "right-judging and distinguishing truth from falsehood", then the outcome of the two studies that pointed out the uselessness of Niaspan was predictable.

Is any of this nonsense getting to our leaders? According to this article from Bloomberg:

 "I don’t know how you can justify it,” Robert Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston and an associate professor of medicine at Harvard. “The balance of the data suggests that niacin has little if any role in” treating patients with cholesterol problems, he said in a telephone interview.

Perhaps our Cargo Cults are running low on faith here in the US and in Europe. The layoffs keep on coming. The money is trickling in at record lows. This sad state of the business of Cargo Cult Science has some saying maybe it's time to head over to China.

Loosely defined, arbitrage is striking a combination of matching deals that capitalize upon an imbalance. Profit is gained from the difference between the market prices. With the Chinese government focusing on innovation through forward-looking national agendas for economic development, the opportunity to apply an “innovation arbitrage” is emerging as an important means to develop novel medicines in China. - Paul Grayson of Cargo Cult RuiYi

Cargo Cult Business? RuiYi hopes to introduce an antibody against IL-6 to protect the indigenous people of China from RA and cancer. IL-6 is one of the latest single cause/drug target being pursued by pharma. The simple side of biotech is to select the target, have some people make an antibody, then set out in your snake oil caravan. The trick is the sale of the product. Beyond showmanship, one must also take into account the audience.

Historically, the potential value of developing a new therapeutic in China was discounted heavily by the potential risk that the therapy would not be used. Chinese healthcare has relied heavily on traditional Chinese medicinal remedies, and the less established intellectual property enforcement did not protect against domestic competition.

There are 1.345 billion people living in China versus 315 million people in the U.S. Imagine how much money we could make if they were simply... us. We make a fortune off of our pills even after studies demonstrate a lack of efficacy and harmful side effects (see above discussion on Niaspan). Are the Chinese people ready for us?

The China Study, by Dr. T. Colin Campbell (controversial as it is here on the CCS) clearly showed a difference between China and the west. Did Paul Grayson of RuiYi take this information into account? A different set of human beings live in China than our current Cargo Cult patients. In order for this latest business model to work we will have to first get the Chinese to eat themselves into the western disease state. The profits made from the Cargo Cult sciences in western pharma were not earned in a day. It takes a long period of time to create the situation that allows for the Niaspan story to A) happen, then B) barely get any attention from the national media. Without the same Cargo Cult Culture, the Chinese may simply ignore the products we bring them. In fact, I predict that is exactly what they will do. While it is true that we have set up many a McDonalds in China, profit from our pills will require that the western diet is first adopted by a certain amount of Chinese people. What is that amount?

We have yet to accept the relationship between diet and illness. The attempt to bring our pills to China is a prime example of how misguided our Cargo Cult leaders have become.

I have been bred up to Letters from mine infancy, and because I was persuaded that by their means a man might acquire a clear and certain knowledge of all that's useful for this life, I was extremely desirous to learn them. But as soon as I had finished all the course of my studies, at the end whereof men are usually received amongst the rank of the learned, I wholly changed my opinion, for I found myself entangled in so many doubts and errors that me thought I had made no other profit in seeking to instruct myself, but that I had the more discovered mine own ignorance. Yet I was in one of the most famous schools in Europe where I thought, if there were any on earth, there ought to have been learned men. - Rene Descartes

Select assets discovered outside China with best-in class-potential that have been passed over due to the competitive landscape could be extremely innovative in China. Identifying, accessing, and partnering such an asset defines an “Innovation Arbitrage” for the arbiter who is prepared for the opportunity. - Paul Gayson

Monday, May 27, 2013

The RQ Test

Jack is looking at Anne, but Anne is looking at George. Jack is married but George is not. Is a married person looking at an unmarried person?" Is the answer yes or no, or can the answer not be determined?

If Anne is unmarried, Jack looking at Anne is a married person looking at an unmarried person.

If Anne is married, Anne looking at George is a married person looking at an unmarried person.

The answer is yes. Without knowing Annes marital status we can come up with a definitive answer.

In this HuffPo article, "Uncommon Sense, Toward an RQ Test", Wray Herbert discusses the work of University of Toronto psychological scientist Keith Stanovich. Dr. Stanovich has coined the term"dysrationalia," to describe a cognitive deficit held by people considered to be highly intelligent but not very smart. The big question is What is rationality and how can it be measured? I believe that this is what Feynman was talking about here:
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 explicitly say what this is, but just hope that you catch on by all the examples of scientific investigation.

He hoped that the graduating students listening to his Cargo Cult Science speech had learned how to berational critical thinkers. It appears that Dr. Stanovich is going to try and further the cause of explicitly saying what is missing in cargo cult science. 

I have a couple examples of cargo cult science in action. I think we learn from the good and the bad 
sciences. The first example comes from a Neurobiology post doc. She had obtained her PhD but did not catch on to "the idea that we all hope you have learned in studying science in school." There came a 
point in her laboratory work where she needed to dialyze a solution. We showed her how to use the 
slide-alizer dialysis cassette. 

In this picture you see the orange cassette suspended in solute via the white foam floatation sponge. 

The next morning we found her cassette spinning above the dialysis solution. She had somehow 
balanced the cassette on top of the white foam floatation sponge where it could not interact with the 
dialysis solute. She had painstakingly kept her solution from coming into contact with the beaker full of solute. She had no doubt learned about osmosis but she missing a mechanical rationality.

The married/unmarried question was probability. If you have 3 boxes you can put either an M or a U 
into, you have 2 (M or U) to the third (3 boxes) power (2e3) or 8 options. 2 x 2 x 2 = 8
  1. MMM 
  2. MMU 
  3. MUM
  4. MUU
  5. UUM
  6. UMM
  7. MUM
  8. UMU
If you only get to look at options with M in the first box and U in the last you have only two 
The only box that changes is the middle box. You have 2 (M or U) to the first (1 box) power. 2e1 or 2.
This can be taught in a math course but rationality comes into play when the probability question is worded in the way of the married/unmarried person. Will you recognize this as a math question that was in your education? You paid for the knowledge, can you now apply it to come up with the truth?
Another biotech example. In this example you have 7 boxes with the possibility of putting any of the 
20 amino acids into each box. You now have 20 (amino acids) to the 7th (7 boxes) power. 20e7 or 
1.28 billion possible arrangements.
Marina Biotech, Inc. (NASDAQ: MRNA), a leading nucleic acid-based drug discovery and development company, today announced that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for patent application U.S. 11/955,207 with claims that cover a library of over 1×10(15) novel peptides.
The reporters got the story wrong. "Novel" peptides refers to the 1.28e9 number. The 1e15 number is an insignificant number that refers to the total number on hand at a specific time. Knowing the difference requires the same logic one would apply to the married/unmarried question.
The Cargo Cult Science rationality dysfunction however took place at the biotech company. They failed to understand the system of phage display, just as the Neurobiology post doc failed to understand the system of dialysis. Dialysis is a system and it works. Phage display is a system and it works. The question is whether or not the user can make it work. Does the user understand the mechanics, math, proper processes and the limitations? If it doesn't work, can you figure out the problem? In both the dialysis and the peptide library example, failure was the outcome. Dialysis did not take place nor did the peptide library produce the promised results. Somewhere within the systems, the users took a wrong turn. They went Cargo Cult. 

Rationality is not an easy subject to pin down. Something so subjective will be hard to identify, let alone quantify. I've been trying for years.


agreeable to reasonreasonable; sensible: a rational plan foreconomic development.
having or exercising reason, sound judgment, or good sense: acalm and rational negotiator.
being in or characterized by full possession of one's reason;sane; lucidThe patient appeared perfectly rational.
endowed with the faculty of reason: rational beings.
of, pertaining to, or constituting reasoning powers: the rationalfaculty.

Monday, May 20, 2013

File Drawer Effect

The "File Drawer Effect" is mentioned on the Arnold Foundations webpage under area they focus - research integrity. The File Drawer Effect according to The Skeptics Dictionary:

The file-drawer effect refers to the practice of researchers filing away studies with negative outcomes. Negative outcome refers to finding nothing of statistical significance or causal consequence, not to finding that something affects us negatively. Negative outcome may also refer to finding something that is contrary to one's earlier research or to what one expects.
They go on to point out a need for policies against the selective reporting of only positive results.
Little research seems to have done on the extent of the practice of scientific researchers to file away studies with negative outcomes.  
I'd like to add something to that definition. Negative can include anything that disrupts the Cargo Cult narrative. We must first begin with an Einstein quote:
"Where the world ceases to be the scene of our personal hopes and wishes, where we face it as free beings admiring, asking, and observing, there we enter the realm of Art and Science." 
We don't just put negative outcomes into the file drawer. We fill our file drawer anything that we feel will jeopardize the way in which we think the world sees us. If you were allowed to look into the file drawer of another person you may wonder why they put this or that into the drawer. Do the things in the drawer effect someone's hopes and wishes?

I want to give two specific examples of things put into a biotechnology companies file drawer. When you work in the laboratory you get to see things being put into an file drawer. We had an RNAi project that was to knock out TNF alpha. The first experiment involved 3 mice genetically modified to overexpress TNF alpha. In time, without any treatment, their joints would swell. Mouse one was treated with PBS (the negative control). Mouse two was treated with Humira (anti-TNF antibody positive control). Mouse three was treated with our RNAi. In this experiment our RNAi treatment appeared to reduce swelling as well as the positive control. We moved from 3 mice to 300. In this experiment our RNAi treatment was produced results akin to the negative control. Experiment two went into the FD while experiment one was still used in slide presentations to outside interests. This is an example of extreme "File Drawer" research. Sadly, the 300 mice, stored individually in 250 ml jars filled with formaldehyde, were stuffed under unused bench space for all of us to ignore. We all saw this file drawer every time we walked past that part of the lab!

This next item in the proverbial file drawer is more telling of the individuals who stuff things into file drawers. We had a cloning project that accumulated a set of vials containing DNA produced by a machine in a laboratory at the Invitrogen Corporation in Carlsbad California. Each vial contained a different lot of DNA. The lot came from a standing order. We would simply ask for more. The delivered product however, was different from lot to lot. Only two of the ten lots of DNA provided an outcome close enough to the desired cloning outcome. In fact, we used the second lot reluctantly after came up short of obtaining the number of clones we needed to complete our project. One undesirable lot contained DNA with an obvious mistake. All nucleotides were thymine. Somehow technicians at Invitrogen had not mixed the nucleotides to randomly insert A T C or G. The other 7 lots had problems stringing together the full length of DNA that was ordered. The two lots that were used were far from what was desired. 38% of the clones sequenced contained DNA sequences that we had not designed.

This, however, is not an unusual situation in molecular biology. We were hyper aware of the situation only because we were making a phage library and could not remove any unwanted clones. The high percentage of unwanted clones meant our library was not what we intended. In the publication and patent however, the unwanted clones were given a name. They were mutants. They had mutated! The ten lots were not mentioned. In place of the simple explanation (man made DNA will contain more errors than PCR generated DNA) a more confusing explanation was offed. This is where I first became aware of Occams Razor.

The "File Drawer Effect" here is not one of simply hiding negative outcomes. For anyone who has ever worked in molecular biology, 6 out of 10 is not a negative outcome. Why describe the 38% non full length clones as mutants? Why did the owners of this file drawer fail to mention the ten lots of DNA? Because it jeopardized the mutant story. There was a need to make this work seem more scientific. The clones did not fulfill their intended purpose. The new purpose was to spin the multi-hundred thousand dollar project as a work in progress.

Putting the negative results from the 300 mice TNF alpha experiment into a file drawer can be explained in ways other than Cargo Cult. The scientists could simply be dishonest or they feel someone did something wrong. The "mutation explanation" is a different kind of "file drawer effect". Sometimes a scientist just wants to seem scientific.

PS: This entire project was finally put into a file drawer in 2007. It was touted as an important part of the RNAi technology package. Then it disappeared... into a file drawer. No value.

Sunday, May 19, 2013

The Arnold Foundation

This article about the Arnold Foundation is a must read. A young former Enron energy trader moved on to run his own hedge fund. In ten years he earned over 4 billion dollars, then shut down the shop. He, John and his wife, Laura, started a foundation to give away the bulk of their wealth. Their philosophy is genius!
The Laura and John Arnold Foundation strives to produce substantial, widespread and lasting changes to society that will maximize opportunity and minimize injustice.
There are three areas of focus: 
  1. Criminal Justice
  2. K-12 Education Initiative
  3. Research Integrity
What first caught my eye was the Yahoo article that began the Arnold Foundations interest in Gary Taubes. I have long been a fan of his and spoke of him as recently as two posts ago. Gary Taubes wrote Good Calories, Bad Calories and Why We Get Fat. Nutritional science is a soft science but Gary now has an ally to help him get his message across via a scientific study. John Arnold took note of Taubes suggestion that a comprehensive experiment was needed to answer some of the key questions about how our bodies process food. To me, this is would be a bold move. Having worked in biotech/pharma, I have witnessed the careful excision of experimental designs that might cast doubt on ones theory. Taubes believes in what he is saying so he is betting the farm on his expected outcomes. At the same time, he is not putting up any road blocks to steer the research towards the expected outcomes. 

Just to give an alternative view, here is a Scientific American blogger who disagrees Gary Taubes and John Arnold. I hope that this individual is asked to participate in the experimental design of the obesity study. A vital aspect of this research would be to not only take into account what your detractors are saying, but to invite them to participate in poking holes in your theories. The theories, by the way, will be tested by the Nutrition Science Initiative (NuSI), a nonprofit headed by Taubes and physician Peter Attia. The research will be carried out by a collaborative group of clinicians and scientists from the fields of endocrinology, metabolism, diabetes, obesity and nutrition. NuSI has received its first two years of funding from the Arnold Foundation.

Besides testing theories on obesity and learning about how our bodies process food, I hope one more area of research will be advanced. How do we take two opposing sides and design experiments to settle the argument? In this case, we have an easy target; obesity. At least, it appears to be an easier target than a group of terminally ill cancer patients. The obese individuals in the study will have to be screened carefully. Once this begins, the arguments over how to group the participants will begin. Smokers, age, gender, genetic make-up and so on, will confound the data and generate suspicion on the conclusions. This is where science begins. Each researcher will have to set aside their bias and think only about the way in which the study begins. Most of the work will come from the planning. Once patients begin their journey, no further planning should go into the research. 

Just as Euclid, Descartes and Newton all sat down one day to write their text books to be sold to the Universities, so should NuSI sit down and describe the experimental design of this study. The human body is something of which we know very little. This study can be used to fight against the single target/single treatment paradigm of biotech/pharma that has painted us all as simple organisms in need of simple but very expensive pills.  What ails us is not TNF alpha, amyloid beta, IL-2 or any of the other popular drug targets. What ails us is a complex system of molecules moving about and somehow bestowing upon us the gift of life. How do we begin to understand how those molecules move about. The science NuSI has to advance is not only nutritional science, but the more complex issue of how to study the human body. Let us branch out from the gene hunters and pill pushers. Let food be our medicine!

Thank you very much Arnold Foundation for your efforts to take the Cargo Cult Science out of research. Your focus on research integrity, and your entire philosophy is anti-cargo cult. 

Saturday, May 18, 2013

Cargo Cult Cancer

In the Cargo Cults, authority is the truth. In real science the truth the authority. The documentary Money and Medicine highlighted many examples of our medical authorities working in cargo cult mode and real science. The authority becomes the truth when we just do not know something. We don't know of any way of dealing with Alzheimer's but we have doctors who still have to treat patients. They even have pills approved by the FDA. That seems to make people feel better, just as a religion. Science, on the other hand, offers up what some would consider confusion. By admitting that we do not know something we run the risk of losing our credibility with the masses. The minority, those who think scientifically, run towards the unknown with a much different attitude. The truth is our authority. If we can reign it in we can harness some of that authority/power.

In the Money and Medicine documentary the authority take a real science view of what a hospital can and cannot do for end of life situations. We can keep people alive, for example, but in ways that do not bring them back to any semblance of a healthy human being. Death is an option that most would prefer. Yet a hospital must offer the option of keeping a patient alive if they can, even when it is merely a technical version of life. To the healthy person looking in from the outside, life is life. They imagine the dying individual being happy and content to lie in their bed looking out from the inside. The healthy person does not imagine what it is like on the inside, laying in bed as your body tries to expire. We simply don't want to accept the fate that awaits us all.

Cancer may very well await us all, if we live long enough.  If we were to study cancer, and not just single genes or other single causes, we could study dormant cancers we all live with. What cancer precursors dwell within our bodies that never progress to the point of taking our lives. In Money and Medicine was pointed out that autopsies on a group of men, post 70 years of age who died of something other than prostate cancer, showed that around 80% had what doctors would call prostate cancer. The advent of the prostate specific antigen (PSA) test has led to an increase in diagnosis yet dubious evidence of having an impact on mortality. The same can be said for mammography and breast cancer. Men and women have separate but equal cancer precursors that may exist as one of many possible expiration devices placed in our bodies to ensure we don't live too long. When it comes to medical science however, the authority can fancy itself to be the truth. They will find these ticking time bombs and zap them with medicine. As we can see with breast and prostate cancer testing, early detection has not provided the doctors with the authority to hand over new leases on life. They do however offer up treatments that enrich big pharma and the hospitals.

We are humans and humans seek patterns. If we can find patterns in those who die from cancers we believe we can prevent cancer from happening. The news of Angelina Jolies double mastectomy is an extreme example of using the patterns we think we see and following up with another pattern we think we see, that of surgery leading to extended life. Angelina Jolies mother died in her fifties thus Angelina is taking a preventative measure to avoid the same fate. The medical authority has given her a new lease on life, but no guarantees that it makes a difference. We can see how the Hippocratic Oath, "I will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone", is subjective. 

This all leads me to an article published by the New York Times last month.  Peggy Orenstein wrote this piece, "Our Feel-Good War on Breast Cancer". She points out that early detection may not provide the benefits that have been touted. Younger women have more density in the breasts thus there are more false positives and false negatives in mammograms.  The question of just how many lives are being saved is itself taboo among breast cancer advocates. Their answer is that early detection works. They have what they want, never mind the statistics. It feels good to believe that what we are doing is working. So why the inconvenient negative data?

From the documentary Money and Medicine:
A number of recent studies estimate that a third of all health care expenditures are unnecessary and that eliminating wasteful spending would save over 800 billion dollars a year. 
Why is that? I continue to think about these things. What have I come up with here today? What is my point? Conclusions? After 7 years on this blog I see only one solution. Keep the negative and inconvenient information flowing. To a true scientific mind, the state of not-knowing is like the state of hunger to a person walking into a restaurant filled with the aroma of delicious food. To the cargo cult scientist, the state of not-knowing is shameful. The cult must turn to the authority who will make the claim that they do know something, it's just that a little more research is needed. Research becomes mere tweaking the old ways that aren't working. My conclusion today is to simply stay thirsty my friends. Remain a skeptic. The state of not-knowing is good. Authority does not represent the truth... the truth is the authority.

Friday, May 10, 2013


The headlines from the featured stories on Biospace struck me as an interesting study for future generations. Today we can look back and scoff of things like leeching or the uproar over whether to wash ones hands before surgery or not. But look at what our scientists are proposing just today:

  • Drinking Champagne Improves Memory
  • Could Eating Peppers Prevent Parkinsons?
  • Soy and Tomato may be effective in preventing Prostate Cancer
  • Fish Oil doesn't help prevent heart attacks
In the future, people might look at this sort of research as we now look at leeching. Each solution to a human condition has a single simple answer. Leeching was suppose to help balance the four humors; blood, phlegm, yellow and black vile. When all humors were in balance perfect health was assured. What if you are experiencing memory loss and the leeches aren't working? Never fear! Science has found an alcoholic beverage to cure that problem. Throw in some red wine, the magical elixir of life, and you might just wake up with a hangover and a newfound skepticism towards this kind of science. 

Each single simple solution began life... as a single simple solution. We are taught this manner of thinking in our education system. Life sciences are easy on the math, heavy on the narrative. As a result it seems that we begin to address problems, such as how memory works, Parkinsons, Prostate Cancer and cardiovascular disease, as if they were test questions. Parkinsons can be treated with ________. Eating peppers can be used to treat __________. We find the answers from simple everyday products. 

Scientifically speaking, the most interesting aspect of this kind of research would be that scientists have found a way to measure disease states. The assumption is that we naturally know how to study health effects one food at a time. At the same time we still have no standardized way of measuring the health benefits of any intervention. If we did clinical trials would be much easier. We could simply fill in the blanks with data from our statistical analysis with an appendix reference to the raw data. The above studies could be compared to other claims on their disease area. Red wine benefits could be compared to the secret of long life (bacon) discovered by this 105 year old Texas woman.

In each case above we have a lack of creativity when it comes to attaching solutions to problems. We have an abundance of creativity in creating the story that the simple solutions actually effect the complex problem. Science should work in the opposite direction. We get creative in tackling problems and rigorously scientific in analyzing our outcomes. 

Much of our problems come from education. This TED talk describes how we have a one-size-fits-all education system that mines each brain for the same things. 

The creativity we employ is not what it once was. Don't tell us about your findings of X treating or curing Y. Tell us how you found a way of measuring the effects of X on Y. That is where creativity is needed. 

Saturday, May 04, 2013

Forks Over Knives Revisited

I have, in the past, touted the miracle "cure-all" medicine of a mostly plant based diet. The documentary Forks Over Knives struck me as a wonderful example of people giving up traditional pill based sick care for "let food be thy medicine" health care. They were careful not to use the word vegan in the documentary, but "Forks Over Knives" is about being a vegan. I have looked into many dietary ideologies and there are many many paths one can take that are better than the typical American diet. The Forks Over Knives path isn't bad but tough for those who enjoy a little more fat. Another path could be the Atkins Diet approach. Gary Taubes produced a very detailed documentation of the history of cholesterol research in his book "Good Calories Bad Calories". What struck me about the two paths was how they stood in stark contrast to one another yet achieved similar results. There was one common trait however. The lack of sugar and processed foods.

I came upon this critique of Forks Over Knives the other day. It's a blog written by a 26 year old former vegan who now survives on a raw food diet with some meat in the picture. She is also an English major taking on the MDs who started the Forks Over Knives movement. Her name is Denise Minger. She is Davy fighting Goliath.

We all share a common belief in the powers of what we eat. We share an interest in seeing people get healthy by taking aim at their behavior. We also have skepticism built into our DNA. We all like positive results, but here is where we must avoid being Cargo Cult Scientists. What matters is finding the most probable reasons for the outcomes we like so much.

The first thing we at the CCS must address is part of the documentary regarding the Nazi occupation of Norway. The message was that meat rationing led to a rapid reduction in death from cardiovascular disease. What was missing was the fact that the rationing of meat began one year after the reduction of death from cardiovascular disease.

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. - R. Feynman

During the first year [starting in spring of 1940] the rationing included all imported foods, bread, fats, sugar, coffee, cocoa, syrup, and coffee substitute. In the second year [starting in late 1941] all kinds of meat and pork, eggs, milk and dairy products were rationed
The question now is how this information was dealt with by the Forks Over Knives people. Did they, as Feyman  instructs, "report everything that you think might make it invalid".  I think this information might make vegans cringe. What other causes could explain these results? Sugar? bread? syrup? Fats? Luckily for us, Denise Minger got the attention of T Colin Cambell. This response was a testament to her work. Unfortunately in his response he failed to specifically address the actual scientific studies that were of dubious quality, yet made it into the film for dramatic affects. 

I'd like to highlight the condescending response and some of the Cargo Cultisms therein. The response begins with a classic ad Hominem logical fallacy, a veiled attack on Ms. Mingers qualifications to question the Great Oz's of medical science. 
Kudos to Ms. Minger for having the interest, and taking the time, to do considerable 
analysis, and for describing her findings in readily accessible language. And kudos to 
her for being clear and admitting, right up front, that she is neither a statistician nor an 
epidemiologist, but an English major with a love for writing and an interest in nutrition. 
We need more people with this kind of interest.
Silly rabbit, Tricks are for kids... and science is for doctors. The Cargo Cult message here is that they are doctors and she is only an English major. Not even an English PhD! 

Next up in the Cargo Cult Science department is the appeal that no specific part of their Cargo Cult ceremony brings the cargo. It is only the complicated intermingling of this-that-and-the-other-thing that makes the narrative work. It's the George Bush Jr. cop-out. Sure we lied to get the war started but now that Sadam is dead, it all worked out for the best. Dr. Campbell organized his thusly:
My response can be divided into three parts, mostly addressing her lack of  proportionality—what’s important and what’s not.    •Misunderstanding our book’s objectives and my research findings    •Excessive reliance on the use of unadjusted correlations in the China database    •Failure to note the broader implications of choosing the right dietary lifestyle 
Let's slow down the straw man argument for a moment and see if Dr. Campbell addresses the above Nazi/Norway dilemma or the following specific question by Ms. Minger:
What we’re interested in is the sentence near the bottom, which the film’s producers apparently didn’t notice: ”In all, 30 rats on the high-protein diet and 12 on the low-protein diet survived for more than a year.”
To which we get the response:
First and foremost, our extensive work on the biochemical fundamentals of the casein 
effect on experimental cancer in laboratory animals (only partly described in our book) 
was prominent because these findings led to my suggestion of fundamental principles 
and concepts that apply to the broader effects of nutrition on cancer development. 

So... what about the damned rats dying?  What about those sugar-free Norwegian vegans? Dr. Campbell says:

The China research project was a cornerstone study, yes, but it was NOT the sole
determinant of my views (as I have repeated, almost ad nauseum in my lectures). In
doing so, and except for a few denigrating remarks on our experimental animal
, she also ignores the remaining findings that I presented in our book. She
seems not to understand what our laboratory research was showing. Using univariate
correlations mostly without adjustment for confounding factors, qualification of variable
authenticity, and/or biological plausibility can lead to haphazard evidence, subject to the
whims of personal bias. Also, univariate correlations of this type can lead to too memphasis on individual nutrients and foods as potential causes of events.  
Why wasn't their a reference for the denigrating remarks? More importantly, why didn't Dr. Campbnell start advocating a high protein diet for rats hoping to increase their time in the vivarium. Dr. Campbell again wants the reader to keep focused on his narrative and ignore the facts found in his research laboratory. 

The "univariate correlations" conversation is yet another attempt to hide the somewhat dodgy research findings that were used in presenting the Forks Over Knives narrative. The only thing I have to add to this discussion is this. If they aren't significant, why did we hear so much about them? This area right here, where we are suppose to ignore the little studies, yet still believe the narrative they support. really starts to get old. If it doesn't matter, tell us why. Don't bring it up and berate us non-PhD/MDs and English majors for asking you questions. You are suppose to be defending your research, not the insignificance of what you publish. 

I must commend Denise Minger for what she has done. She is Davy fighting the mighty Goliath. I think we can all agree that we care about food as medicine and being healthy. So much passion has Denise for this issue, that she took on a highly popular movement that is in fact a million times better than the diet on which I was raised. I would like to say something nice about Dr. Campbell but I'll end with something he said to Ms. Minger ... which was very Cargo Cult. 

I should conclude by noting the suggestion of the professional epidemiologist, cited  above, who suggested that ultimately Denise may wish to publish her findings in a peer- reviewed journal but who presently felt strongly that the current version would not be  accepted. I concur. 
I have never tired of my own narrative, that most of what gets published is pure bullshit. We all know that science journal editors do not practice the scientific method and thus Ms. Minger does not have the proper credentials to get published. We also know that Dr. Campbell does. What he is suggesting here is that, once again, he is a doctor and she is an English major. You win that one Dr. Campbell. You have surprisingly rejected her paper.
She sure did get Dr. Campbells goat though.
In honor of Ms. Minger, I'm going to sprinkle a little goat cheese on my salad tonight.

Wednesday, May 01, 2013

Biospace Report 2013 Report On Jobs

Without proper bean counting techniques, it is hard to say how many people have come, gone or stayed in the work force that makes up biotechnology/pharmaceutical science. You could first set up a list of career paths. Let's say one person has an associate degree in biotechnology. The next person has a BS in Chemical Engineering. The next person has an MD. The next a PhD in Pharmacology. Make a second list of possible job opportunities and match up the degrees with the jobs. Then make yet another list of jobs and match up the education backgrounds and job experience with the next leg of the journey of a career.

What is the life span of a particular career and how many should be expected to support the companies that currently exist? Should we expect more or less companies in the future?

According to Biospace, the future is looking brighter. "Biopharma recovery continues with unemployment rates falling over three percent," said Chanille Hewett, Biospace Product Manager. Our salary data shows further recovery indicators; since bottoming out in 2010 biotechnology salaries hit a three year high in 2012. Not only are our professionals getting back to work, but their pay is trending upward as well."

How did they ignore the large number of layoffs during the time period of 2010 to 2012? Does their methodology really tell the true story. It would seem that there is a built in bias. A Biospace Product Manager may be under pressure to tell the "best story". Journalism is not what it used to be. According to Xconomy, Biotech was back in 2010, but has been on the decline every since. Over 150,000 jobs were shed from 2009 to 2012. How is the Biospace "recovery" treating the lost 150,000 jobs?

Using Seattle as an example, less jobs are posted on the WBBA website than ever before. Knowing people in the area, I can identify some of the jobs as being mere place holders on the WBBA website to give off the appearance of a viable company. In reality the jobs have sat on the website for months with no effort being made in-house to fill those positions. Out of 17 companies listing jobs on WBBA, nine companies only have 1 job vacancy, four companies have 2 jobs, leaving the remaining four companies offering 3, 7, 10, and 28 jobs. Take out Seattle Genetics and you've got 37 jobs from 16 companies.

Why bring up a non-factor like Seattle? The area was never a viable hub for generating large numbers of jobs. Old job creator like Institute for Systems Biology no longer have life science opportunities. I have seen people searching for "Institute for Systems Biology layoffs" on my blog. None have been reported. Hmm. If you look at jobs on the Amgen site you will see many that have been listed for years. Lazy human resource practices and embarrassment over the lack of forward progress have added to the confusing calculations done by Biospace. If there is a problem reporting the proper numbers, then larger hubs such as San Diego, San Francisco, North Carolina and Boston, might be adding larger amounts of bad data to the calculations being made by Biospace.

Using the scientific method, we can look into the realities of bio/pharma.

My observation is that there have been far too many layoffs to conclude that in 2013 everything is on the  mend. The measurement of recovery hasn't been defined. Imagine the recovery from the past few years being the inverse of the layoffs. Pfizer hires 19,500 people!

So I have to ask a question. I start with several questions. "What are the jobs that were lost?" "What are the new jobs?" In general, "Has the biopharma workforce changed what is does?"

Using the Cargo Cult analogy, "Have the Cargo Cult Airports figured out how to conduct themselves in a manner that puts more wealth into their system?"

By looking at the new jobs, we have a better way of judging the future of the business. Have we redefined how a person is to stand in the watch towers or have we figured out what the Westerners were actually doing in their watch towers?

My hypothesis is that things have not gotten better, in general, that the workforce has lost valuable experience. The Dilbert-esque bosses have kept their positions while the people, whose minds made up the knowledge base of what really needs to get done, have lost their jobs. As the money fades away, careerism overshadows what is truly needed at the company. Those with the power to choose will always choose to keep themselves around and get rid of those below. Proving ones value does not get done via the scientific method.

Check what people are saying online. Biofind Rumor Mill:

We had two openings for entry level (bs +1/2 years experience) molecular bio techs. We received over 100 resumes, over 30 of which were from PhD holders. We hired people with bs + 2-5 years experience. The overdegreed candidates didn't even get to the interview stage.
In the last 5 years, jobs in science/pharma/biotech have declined resulting in a surplus of unemployed PhD and MS scientists. We need to have some organization that will help MS/PhD scientists get jobs in the fields outside of their expertise with some training while working. A person who has done MS/PhD can certainly learn other skills in 1-2 years and succeed in other fields.

If you continue reading the thread from Biofind you will see a trend. Over-education is detrimental to your hiring prospects. Training is not provided quite often. The industry where you hope to have a career is not booming. Some will win, most will not, and the winners aren't training the losers how to succeed.

What is the experiment? Well... I started this blog in 2006. That has been the experiment. Was I able to find a problem other than my own career falling by the wayside? The industry has proven, in spite of reports of its constant rising from the ashes (without any reports of a fire) that it is a poor investment. The money has dried up. Bad science leads to bad investments. The intolerance to the loss of capital is a good thing. New initiatives, such as the Reproducibility Initiative and the latest initiative from the journal Nature to improve the reproducibility of their published papers, are starting to pop up. The Amgen study boldly went where few professional scientists would dare go, and they were published. Retraction Watch now shines a light on things we know... that aren't so. People are starting to do what they have been reluctant to do in the past, admit our faults. Ben Goldacre has published Bad Pharma that has opened the eyes of regulators to the plight of anyone who wants to get the to the truth of a big pharma clinical trial. Aubrey Blumsons war against Procter and Gamble opened the door for questioning big pharma trials and their lack of transparency. Cargo Cult companies like SIRNA and Sirtris have closed up shop, costing their big pharma purchasers huge write-offs. Beyond biotech/pharma, medical practices have also been scrutinized in books like Checklist Manifesto and Unaccountable. 

In general, we are not on the mend as often reported by Biospace and other people who benefit from maintaining the status quo. We are in the process of changing, getting rid of bad science, and a whole lot of bad scientists. The old ways were unsustainable. We are learning to be more honest and hold others to the same standards. The experiment continues.