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Friday, January 31, 2014

Biotech Royalty

David Blech earned the title "The King of Biotech". Armed with a Masters degree in Music Education, he became a member of the Forbes 400 investing in companies like Genetic Systems Corporation, Icos, and Celgene. In 1990 he founded D. Blech and Co., a registered broker-dealer involved in underwriting biotechnology issues. On September 22, 1994 the company was deep in debt and ceased operations due to net capital rule violations. The day is known as Blech Thursday.
The uniform net capital rule is a rule created by the U.S. Securities and Exchange Commission ("SEC") in 1975 to regulate directly the ability of broker-dealers to meet their financial obligations to customers and other creditors. Broker-dealers are companies that trade securities for customers (i.e., brokers) and for their own accounts (i.e., dealers).
Blech was given a five year probation sentence in 1998 for criminal fraud. In May 2012 he pleaded guilty to manipulating shares of biopharmaceutical companies Pluristem Therapeutics Inc and Intellect Neurosciences Inc in 2007 and 2008. 

The Cargo Cult message of the story is that success in biotech financial matters does not require a PhD from MIT. It does not require bend-over-backwards scientific honesty. It requires the mind of a gambler. Remember the successes, but not the failures. Remember random events around your successes and tout them as skillful tricks of the trade you are in. 

In Seattle there is a building with four numbers in front. 



Inside this building are people who have chosen the same career path as David Blech. Carl Weissman and Steven Quay have been at the helm of several costly biotech investment decisions. Neither has found themselves on the Forbes 400 but they have had lucrative careers in biotechnology. The investments they have attracted have not been lucrative. Weissman is now the former CEO of Accelerator and Quay is in charge of a sinking ship known as Atossa Genetics. 

I don't want to go into further details about these investment opportunities. I've written about them before. Each man is a leader, as defined by the terms of a CEO. You are investing in them and the decisions they make with your money. Like David Blech, they are not scientists, as defined by the terms of a CSO. They seek money and use it to build biotechnology companies. The science is none  of their  business. Their careers have seen hundreds of millions come and go. They want you to focus in their ability to make the money come, never mind how it goes away.

The takeaway from  Blech, Weissman and Quay is that leadership matters. What makes a good biotech leader? In 1992 David Blech would have been considered a great leader. In their rise, Weissman and Quay were considered worthy of stewardship over millions and millions and the careers of many very smart people. In the ruins of their management is the loss of that money and the ruined careers of too many scientists. True, Blech (the music education master) started companies that made money and continue to do so. But he did not do the work that made these companies long term successes. These three individuals are prime examples of the short term mentality. Start company, get out before the fall. They are prime examples of why we need standardization, certified laboratories with certified lab workers. We need to create an career path for scientists who have the power of science to help investors avoid the song and dance of these three men. One of these men is in prison, one is looking for work, and one is draining $600,000 per year (CEO and CSO salaries for he and his wife) until the latest round of financing is depleted. Be assured that all three will continue to fight for their livelihood and raise money to spend on short term money making biotechnology companies.  

There is a little bakery on the bottom floor is 1616 Eastlake called Grand Central Baking Company. They are the most profitable company that has ever done business out of 1616 Eastlake. They have outlasted all of the Accelerator companies. They have a passion for what they do. 
More than two decades after our founder Gwen Bassetti introduced the Como loaf in Seattle’s historic Pioneer Square, we are still locally owned, led by a unique mixture of family and friends, and dedicated to the craft of artisan baking.
Biotech royalty, like Bech, Weissman and Quay, have a passion for the deal. They love being the biggest boy at the big boy table. But this isn't the craft that makes biotech success stories. The craft of "the deal" has led to many a lawsuit, jail time, and high unemployment. What makes any technology company succeed is a dedication to the science and technology behind the product. For this, you need someone outside the royal families. 

Friday, January 10, 2014

The Narrative of Jack Andraka

I would never do a PhD. I’m sorry, but the lab bench is not cut out for me. I don’t want to do academia. I want to work in the clinical field and do business or public advocacy. - Jack Andraka

When I first saw Jack Andraka on 60 Minutes running down the isle to collect his award at the Intel International Science and Engineering Fair 2012, I thought I was watching someone who had just won the Miss America pageant or a chance to bid on The Price Is Right. His demeanor was that of an attention getter. My bias is that I do not like that kind of personality. Rather I gravitate towards Feynman, who did not like awards. I gravitate towards Frederick Sanger who said, "Scientific research is one of the most exciting and rewarding of occupations." I like Einstein who said that true art and science begins where our hopes and dreams leave off. This 16 year old spent 3 months in the lab and a year on the TEDx talk circuit. He was a media darling, but was he a Cargo Cult Scientist?

I've given my bias. I will try to avoid it when making my argument. 

This article from Mathew Herper in Forbes deviates from the positive spin from the popular media that greeted Jacks entry into the scientific community. The title, "Why Biotech Whiz Kid Jack Andraka Is Not On The Forbes 30 Under 30 List".
But I decided not to include Andraka on the list, overriding the recommendation of an expert judging panel, because the work was not yet published in a peer-reviewed scientific journal. It is by published work that scientists are judged.  I still think this was the right decision. In fact, when Andraka volunteered to share a draft of a paper that he does plan to submit to a scientific journal, my concerns deepened.
Here are a few reasons why he is on the Cargo Cult Scientists list:

1) So we really ought to look into theories that don't work, and science that isn't science.

As Mathew Herper points out in his article, Jack Andraka has not yet published his work. Many scientists that reviewed an early version had their doubts about some of the claims. The question science asks, "Does the theory work?" We don't know.

2) Now it behooves me, of course, to tell you what they're missing. But it would be just about as difficult to explain to the South Sea islanders how they have to arrange things so that they get some wealth in their system. It is not something simple like telling them how to improve the shapes of the earphones. 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. 

Jack Andraka is a young man with little experience in science. Something is missing in his foray into science.

3) Details that could throw doubt on your interpretation must be given, if you know them. You must do the best you can--if you know anything at all wrong, or possibly wrong--to explain it. If you make a theory, for example, and advertise it, or put it out, then you must also put down all the facts that disagree with it, as well as those that agree with it. 

Mathew Herpers article highlights some critical details that others have had to point out that throw doubt onto Jack and his mentors interpretation of the lab work.

Andraka’s “168 times faster, 26,667 times less expensive, and 400 times more sensitive” figures are based on a comparison with ELISA. But Church saw problems with the way that Andraka characterizes the ELISA test.
Test speed: Andraka says he compared the speed of his test to the amount of time he spent trying to get results from an ELISA kit he ordered online: 14 hours.  But usually a modern ELISA test takes 1 hour.
Test cost: Andraka is comparing the commercial cost for a test – including the manufacturer’s profit and overhead – to his own materials cost. That’s not a fair comparison. He says the only mesothelin test that he found cost $912 per kit. But other ELISA tests are for sale online for $400 per 60 tests or $600 for 96 tests – in other words, about $6.50 per test run. That still compares favorably to Andraka’s $3 per 10 tests, but remember that there would also be a commercial markup if a company decided to sell his tests. 
4) In summary, the idea is to give all of the information to help others to judge the value of your contribution; not just the information that leads to judgement in one particular direction or another. 

Since the work of Jack Andraka has not been published, we need more information. His mentor, the media and the public all want to believe we have a genius in the wings. The stories and awards provide us with the information and judgement in one particular direction. The truth might fall short of this story.

I agree with Mathew Herper, it was a pretty neat thing for a teenager to do. To take an interest in biotechnology and cancer detection at 15 is remarkable. The tenacity to present his idea to a hundred scientist before getting the attention of one is why I think the kid is going places. His science probably won't go nearly as far.

Which leads me to the conclusion that the boy has merely been a pawn in the Cargo Cults of Biotechnology. His mentor did not discourage the boy nearly as much as those meanies who came later. But that is how science must work. The truly talented scientists have a passion for this pursuit. They do what they do because they are good at it. They want to work in a laboratory, design experiments, observe what  happens, and live a life learning new things that no one else has thought of yet. The details that separate science from Cargo Cult Science are subtle, often times the cause of eye rolling among non-scientists. Where some will say, "big deal" a scientist will demonstrate just how big of a deal a seemingly small detail can be. These people are often introverted, soft spoken, and more focused on petri dishes than their own reputation.

As one commenter said from the Forbes article: "Based on your description, the kid sounded pretty promotional. I don’t know if he will become a scientist. I have a feeling he may become one of those slick biotech CEO in a few years."

A scientist is not a CEO of a biotech company, a bureaucrat at the NIH, or a judge of a science fair. A scientist might hold one of these titles, but the titles do not make you a scientist. Each title may require the holder to have a PhD. But science is bigger than titles and awards and the people who strive for them. A scientist is merely a life long student of the natural world that still has a billion secrets left for us to figure out. 

Through art and science in their broadest senses it is possible to make a permanent contribution towards the improvement and enrichment of human life and it is these pursuits that we students are engaged in.Frederick Sanger 




Sunday, January 05, 2014

The Power of Science

I've often cited the Begley and Ellis Nature paper, "Drug development: Raise standards for preclinical cancer research".  Glenn Begley has graced Xconomy with an article on scientific reproducibility. 

The concept that science must be reproducible before you can call it science is a slippery slope to some. A comment from the Nature webpage listed above:
The claims presented here are pretty outlandish. Particularly relevant to "Hematology and Oncology" we now know that mice housed under different conditions with different microflora can have vastly different outcomes in any model, not just cancer. To suggest academic incompetence or outright unethical behavior is offensive, and is a particularly narrow view of why experiments are difficult to reproduce. Further, as indicated in Table 1, the entire definition of not-reproducible hinges on a priori profit motive of "robust" differences (whatever that means). There is always room for improvement in science, but this entire article is disingenuous and belittling to those of us who are on the front lines.
To this I would respond:

"The manager accepts the status quo; the leader challenges it."Warren G. Bennis


Here is the enemy. Feynman described the mouse maze experiment where confounding factors lead many researchers astray. Finding out where we can go astray is an important part of the scientific method. If you don't rule out as many confounding factors, you are subject to making mistakes like those made by not knowing the effect of microflora on mouse experiments. Will a study on microflora get you a tenured position or will it make you a thorn in the side of the scientists who are more concerned about their career in cancer research? Most likely the latter is true. It is the responsibility of leadership to create a more welcoming place for real science, that may not jibe with the career/corporate aspirations of less rigorous scientists.
It is important to realize that this debate, highlighting the deficiencies our scientific process, is taking place openly within the scientific community. This is a sign of the strength of our scientific system.
That is a very important point. People are embracing the conversation about our shortcomings in science. We need more humility, more honesty and less arrogance. A call for increasing the rigors of our soft science is only going to be a positive for the good name of science. The people who will be hurt by a push in the direction of the scientific method are those who do not appreciate what it can do.

The above commenter may believe that any dissenting view of modern science is heresy. (I don't want to create a straw-man argument, thus he may...) If the argument against increasing reproducibility, increasing transparency, and increasing rigor, is that it would make working in science too hard, then I would argue that the power of real science is misunderstood. Your boss may want to see a positive result from your mouse study on his desk prior to his/her next board meeting. You may have just discovered that the microflora is confounding the reproducibility of your experiments. What do you do?  Is it wise to assume that everyone believes that the newfound knowledge of the microflora will be received with open arms from the guy who didn't ask you to look into such details? In this case, the scientific method is in opposition to the political method. The Machiavellian tactics you employ to advance or simply to keep your job are often times jeopardizing future research, yours and those in your field.

The questions Glenn Begley asks:

What constitutes reproducibility?
What, if anything, has changed?
What is driving this?
What is being done and where will this take us?

What Glenn Begley is doing is very important for others who currently work in, or one day hope to work in science.
The majority of scientific discoveries in the biomedical sphere should be sufficiently rigorous and robust to allow other investigators to build on that work and move the field forward. Hopefully the changes instituted as a result of this debate will help further strengthen our discovery processes. - Glenn Begley
Status quo, you know, is Latin for 'the mess we're in'.
Ronald Reagan
If there is dissatisfaction with the status quo, good. If there is ferment, so much the better. If there is restlessness, I am pleased. Then let there be ideas, and hard thought, and hard work. If man feels small, let man make himself bigger.Hubert H. Humphrey 

Tuesday, December 31, 2013

Marie Hubers SEC Fine

The website Logical Fallacies is an invaluable tool for any scientist or person who wishes to battle the status quo and those who most benefit most from maintaining the status quo.  As stated in the opening paragraph of the website, "Fallacious reasoning keeps us from knowing the truth, and the inability to think critically makes us vulnerable to manipulation by those skilled in the art of rhetoric." Let's look into the logical fallacies surrounding Dendreons Provenge saga.

We have two sides, Dendreon and Marie Huber. One is a once-multi billion dollar biotech company. The other is a private citizen who took issue with the reasoning behind the approval of Dendreons Provenge. Both sides of this story have presented a scientific sounding argument in peer reviewed journals. Both sides appear to have had a monetary motive for practicing the art of deception. Both sides have been accused of some serious shenanigans. In the end, Dendreon is a company on the verge of bankruptcy and Marie Huber has been dragged through the mud.

Here is the final verdict as posted by a pro-Dendreon bully on the Wikipedia site:
Huber's contentions were ultimately exposed as a scheme to profit from speculation in put option contracts in the underlying security of Dendreon Corporation, which would have produced enrichment in the event the stock price were to have declined; the SEC accordingly found in November 2013 that in their reporting of Provenge, she and a colleague, via the dissemination of untrue statements and omissions of fact as a means to obtain money or property, violated Section 17(a)(2) of the Securities Act of 1933 (Securities Act), and imposed against each of them a six-month suspension, a $25,000 civil penalty, and a cease-and-desist order. - Wikipedia entry for Provenge 
"Hubers contentions were ultimately exposed as a scheme to profit from speculation..." The author here is referring to Ms Hubers "Alternative Explanation" as "contentions. This is an important point. The SEC report on Ms. Huber states:
After reviewing and analyzing the FDA documents, Huber concluded that 
the Provenge treatment was hastening the death of patients.  In June 2010, Huber began 
drafting a report for HFA-A, entitled “Provenge PhIII Trials – The Alternative Explanation 
of Survival Results” (hereinafter referred to as the “Alternative Explanation”)
The SEC report later makes the distinction:
A version of the Alternative Explanation was subsequently published in the “Journal of the National Cancer Institute” on February 22, 2012. The findings in this Order do not address the conclusions set forth in the Alternative Explanation. 

The SECs claims against Ms. Huber was that she tried to profit from her June 2010 Alternative Explanation report.
During the period of June 17, 2010 through July 12, 2010, Huber purchased $125,431 in July Dendreon put options and $110,627 in August put options.Huber also purchased put options in her mother’s account, and shared her analysis with friends and family who subsequently traded in Dendreon securities. The July put options that Huber purchased were set to expire on July 17, 2010, and had strike prices ranging from $10 to $30. All of the put options were “out-of-the-money” and most of them had strike prices of $25 or less.   Dendreon common stock was selling in the low to mid $30s.
Ms. Huber did her analysis in June 2010 and purchased put options in July. The argument that the Alternative Explanation report is thus a "scheme for profit" might seem logical on the surface. The problem is that the Alternative Explanation exists separately. Was it developed in order to short the stock? Or was it the impetus to short the stock? We don't know nor have we, nor the SEC, attempted to sort that one out.

The logical fallacy is called the Genetic Fallacy. This fallacy is committed when an idea is either accepted or rejected because of its source, rather than its merit. The idea that we are most concerned about here is the truth behind Provenge. Does it work? Is it safe? We mustn't make the Appeal to Authority and accept the FDA ruling, nor can we assume that the demise of Dendreon means Provenge doesn't work. Locially, there is still work to do regarding the Dendreon Provenge saga. One path we should take is in the practice of clinical trials and how a biopharma company interacts with the FDA. But we'll save that for another day.

I think the Genetic Fallacy addresses the Wikipedia damnation, along with all of the other detractors who wish to write off the scientific arguments made in the JNCI paper. The Alternative Explanation and the JNCI paper have not been called into question. The science is not the issue behind the SEC smackdown of Ms. Huber. The scientific method is a journey. It begins one day with a hypothesis. You test your ideas and maybe one day you decide to publish them. The merits of that journey remain untouched by Dendreon bullies and Wikipedia ghost authors.

Now then, as for Marie Hubers SEC troubles. Marie Huber recently made the following comments on the CCS from this post. 
  • A trial would have cost me at least a year and $100,000 -$250,000 in legal fees.
  • Settling cost me $25,000 and a 6 month suspension.
  • My legal defense bill over the 3 years of this SEC investigation has run into SEVEN FIGURES.
The terms of settlement prohibit me from making any statement other than "I neither admit nor deny the SEC's allegations". This means that YOU KNOW NO MORE AFTER READING THE SEC's ALLEGATIONS THAN YOU KNEW BEFOREHAND. An allegation, by definition, need not have anything behind it but the alleger's motivated imagination. Again, "I neither admit nor deny the SEC's allegations".

July 14/15, 2010: An anonymous report that I had written (exposing hidden results from the Provenge trials) was emailed to a bunch of biomedical folks (only 2-3% of whom were investors).

July 15, 2010: my employer files my report with CMS, identifying us as investment advisers.

August 5, 2010: I log the i.p. addresses of Kroll (private investigators) and Marsh McLennan (their former parent company), trawling through decades of archives of my personal website (www.mariehuber.com)

August 10-20, 2010: i.p. addresses from Seattle, WA, hit my personal website.

August 12, 2010: "Someone from Dendreon Corp" browses my LinkedIn Profile.

Sept 14, 2010: Mitch Gold approaches me, out of 300+ analysts who had just listened to his presentation at the Morgan Stanley conference (he does not know me, but I wear my distinctive long, curly hair down in order to lure him, and he obliges). After a little fun, Mitch reveals that he knows that I wrote the anonymous report on Provenge.

October 6, 2010: [I only learned this in 2013] the SEC contacts gmail regarding the account Jess had created to email my report.



The SEC settlement over my friend's distribution of a report I had written in 2010 is unrelated to my JNCI publication.

The JNCI publication occurred 1.5 years after my puts had expired worthless. I had no financial interest, in any way, around the time of the JNCI publication, or which could have been influenced by it. I was completely truthful in my disclosures to the journal, and given that the SEC had been all up in my business from early 2011 onwards, the settlement acts as PROOF of this.

I wished I HAD written in bold at the top of my report: "I believe so strongly in the shocking nature of the data that Dendreon has hidden and the only logical conclusions to be drawn from it, that I have bought thousands of puts betting on a decline of 30-80% in the price of DNDN stock over the next month". Maybe if i'd written that some people might actually have read it.

Anyone that did read it and understand it would have saved themselves from a 66% decline in the value of any DNDN shares they held in August 2011, when the "efficacy" of Provenge spoke for itself.
---------------------------

She ends with a logical fallacy of her own. The stock tanked in August because Mitch Gold made some promises he couldn't keep. He priced his product too high and didn't give his sales team a chance to make money. The efficacy of Provenge may have contributed to the doctors decisions not to prescribe the treatment but a stock price has no logic. 

I believe Ms. Huber and her analysis of Provenge. She was brave to take the journey, even though she may have tried to turn a profit Wall Street style. What matters here is the way in which clinical trials are conducted and reported to the FDA and the rest of us. Big Pharma has the same for-profit motivations as anyone trying to short their stock.


Monday, December 23, 2013

Mala Aria, Italian For Bad Air

When the ancient Romans were conquering the world they became familiar with the disease malaria. They noticed a correlation between thick musky swamp air and the disease. They deduced that the bad air, mala aria in Italian, was the root cause of the disease. Whenever they encountered the disease they drained the nearby swamps. The solution worked. Of course, scientists later honed in on the real culprits, blood parasites transmitted by anopheles mosquitoes.

Rene Descartes said, "Good sense is, of all things among men, the most equally distributed; for every one thinks himself so abundantly provided with it, that those even who are the most difficult to satisfy in everything else, do not usually desire a larger measure of this quality than they already possess."

One of the greatest obstacles of drug research and development is in the assumption that we know how to do it. Coming from the billions and billions of research dollars and the thousands of disparate workers trying to make money for their employers, is the occasional FDA approval. From the approvals we occasionally get a new treatment that is useful. Like blaming the bad swamp air for malaria, we miss the mark when assigning cause and effect. If we dig a little deeper we find that only science brings about real change.

When a company fails to beef up their pipeline, the C-level execs take action to get rid of the dead wood. In the process, they may very well be axing the only chance science has to do what it does. In that moment, where people and ideas turn over, the C-level execs want you to believe that they have done some good. They are draining the swamp. No one has yet figured out how to research disease and develop drugs without simply spending money, starting and ending projects, and hiring and firing the usual suspects. We don't know what it is that made us succeed at the last project nor why we may be failing at the current one. We succeed quite randomly, if we are to be honest about our profession. If that is not true, and we in fact do have drug development experts, where are the lessons offered by the enlightened? Are we not in need of a larger measure of this quality than we already possess?

There are those, however, who lack the skepticism of the scientists. They are the capitalists.  They will soon be gathering at the 32nd annual JP Morgan Healthcare conference in San Francisco, Jan. 13-16. Luke Timmerman, industry cheerleader, announces the upcoming event:
So what about all the healthcare industry capitalists? Are you ready to make the most of this week when all the decision makers and big investors are together in about a five-block radius?
So much for journalism, this is going to be a love fest. The leaders are gathering. It is time for all good soldiers to make a good impression. The healthcare industry however, is one of many elephants in the room when thinking about the next American crisis. Scientifically, we still do not have a viable career path for our scientists. Financially we have a group of fools and fanatics gathering in a five block radius to talk about ways of profiting from a national disgrace, our healthcare industry.
The whole problem with the world is that fools and fanatics are always
so certain of themselves, but wiser people so full of doubts.
-- Bertrand Russell 

Luke has some advice for the decision makers, big investors and those who want to bend their ear.

Don’t get overscheduled. I’ve made this mistake many times. It’s normal to be such an eager beaver that you pack your entire calendar with 1-on-1 meetings, in 30-minute blocks, from 7 am to 6 pm every day. And that’s all before the evening receptions. 
What will the leaders, investors and journalists who reside over our healthcare system discuss. A reproducibility initiative to strengthen the scientific foundation of the industry? New ways of strengthening the scientific labor force? How well things have gone in the last 32 years? The leaders, investors and journalists may simply be there as the proverbial "bad air", dense, powerful, yet not directly responsible for the success of the industry. For 32 years the leaders have been gathering to inspire one another, resulting in a disastrous system of healthcare. But that is not what they are gathering to talk about.
This conference is one of the largest and most informative healthcare investment symposium in the industry, bringing together global industry leaders, emerging fast-growth companies, innovative technology creators and members of the investment community. 
Approximately 300 companies, both public and private, will deliver presentations to an estimated more than 4,000 investors.
Wouldn't it be interesting if these 300 companies delivered presentations to an empowered, non-biased, career stabilized group of scientists tasked with assessing the science?

Thursday, December 19, 2013

Dying Days

Each day my dad awakes to a breakfast of roughly 20 medications. He spent his life smoking, eating a diet of mostly processed food, and not exercising. Now at the age of 72 he is a very sick man. He's had several heart attacks, heart surgery, he has COPD, and his circulation is very poor. He has been in and out of hospitals and nursing homes 13 times. Each time he is released, he goes home and smokes, eats process foods and watches tv until his body gives out again and he has to dial 911. He has racked up bills of well over $700,000.

I've come to live with him to take care of him. Unlike the doctors, I follow the details of my dads end of life experience. His doctors have provided him with the prescriptions. Every now and again he visits them at the various hospitals where they work. They ask him how he's feeling and he tells them he feels terrible. He wants to hide things he thinks will jeopardize his autonomy, like that he has fallen. The brief conversations between the doctor and patient lead to the western solution to every malady, medication. A complex system, the human body at the end of its life, is treated by a simple system. Take old person to doctors work place, read a few vitals, have a talk, prescribe and/or adjust medications that are currently available, and/or maybe schedule a surgery.

The last nursing home experience seemed to transform my dad from a very sick patient to someone whom the authorities deemed acceptable to live on his own, with his sons assistance. Things have gotten worse in this first week. What took place inside his body? The excitement of going home after 2 1/2 months energized my dad. Day one back home he went through his mail, talked on the phone to family, and finished off the day with in his easy chair watching his tv. He also ate a double cheeseburger. The next day he began to feel worse. Since then he's been eating less, sleeping more and he has become far less steady on his feet. Was the cheeseburger a mistake? What took place at the nursing home versus my dads home? The pills and their doses were adjusted, but what was the real change that brought about the improvement?

Confounding factors, such as diet, exercise, and emotional state have not been considered. Some of the pills are simple compounds found in natural food such as KCl and folic acid. What if the patient has decided to give up their wicked ways and eat plenty of fruits and vegetables to get these nutrients? Would that alter the prescription? Then we have the Zoloft to treat depression. It's depressing to be this sick. Perhaps it is unnecessary to pharmaceutically deal with the fact that you are in need of so many pharmaceuticals. Let the patient be sad. Sadness, perhaps, is not a medical condition. To a doctor and the healthcare industry he, as a generic patient, has been understood. Sad? Zoloft. Next problem. To those of us outside looking in, the problem is that he is also a living breathing thinking human being. At the doctors he is probed and interviewed at regular intervals. New paths are set. If he gets worse, its because of the illness or the lack of following the path. If he stays the same or gets better, it's due to the path. Unknown to the doctors is the path outside of their purvey that might have an equal influence on his physical and mental well being.

I think of myself, this blog and why my message does not have an impact whatsoever. I have good points. The industries of biopharma and healthcare are sick. They need to be cheaper, more effective and offer more opportunities. More communication is needed. The science needs to be more rigorous. In spite of my reasoning and the solutions I have proposed, I am not taking into account the confounding factors. Society doesn't like a nattering nabob. An anonymous blog is a poor format to influence others. Just like the doctors and their pills, I am not taking into account the complexity of the system of which I speak. I might have a good remedy, such as the concept of certification of laboratory staff and their work, but I did so here on this blog. Like an ineffectual medicine, I introduced my remedy in the wrong place. It cannot reach the location where it will do the most good. Likewise, a medical remedy may work at a cellular level, in a mouse or culture dish, but how will we get the same mechanism of action to work in a person?

Note: That's just an example of a system that also doesn't bring about change. I write the blog for practice getting ideas out of my head. 

The Cargo Cult message here today is a lesson I am learning as I watch my dad struggle. It is not enough to memorize the parts of an airplane and what they do.

You can learn about the parts, who makes each part, what the name is in Spanish and know nothing about what makes the airplane fly. Now look at the human body:

Each part has its own doctor. The body however is more than parts. That is the area in which the Cargo Cults of medicine must study. What makes a body live, think, age and eventually die?

Doctors and pharmaceutical companies are also mere parts. The leaders of healthcare must invest in understanding the system of healthcare itself. How does the system effect an individual, such as an old man who takes 20 pills every morning. In time we should advance our understanding of life and death, the system we have to  deal with it, reduce the amount of pills, and paradoxically treat the body through all of its stages of life.

Friday, December 13, 2013

Zuckerbergs Nobel Prize in Life Sciences



I don't like honors either. From the Cargo Cult perspective, awards can be given in spite of the arrival of cargo. Imagine an award given to the tribesmen of Vanuatu for best ceremonial dance or best costume. The real award for the tribe would be the cargo. Without the cargo, an award will assuage the tribe and make them feel as though the leaders know what is being done right and what is being done wrong. The truth is that the leaders of Vanuatu do not know right from wrong, as we do in the west. They do not know what makes an airplane fly. Any such award ceremony would simply be another cargo cult ceremony. The people who decide on the winners of any award sell themselves as the deciders of good and bad. That in itself would be a great honor, to be able to tell the world what really matters.

Mark Zuckerberg and Co. have used their money to bestow an award to scientists. The Breakthrough Prize in Life Sciences is no doubt an award that the Silicon Valley gurus hope will solidify their names in the annals of scientific history. The judges who pick the winners will be the previous winners. The first 11 winners were selected by the founders, I assume. You can bet that there is quite a stir among the Nobel committee members over an award given by a group of Silicon Valley rich kids. Who gave these guys the right to create a life sciences prize? Money? Will there be an overlap of Nobel Prize winners and Breakthrough Prize in Life Science winners? Are they suppose to be on par with one another? Money-wise, the new kids on the block offer a better payday. Oh my.

The prize comes with a $3M paycheck, meant to excite young people about a career in science.
The prize is administered by the Breakthrough Prize in Life Sciences Foundation, a not-for-profit corporation dedicated to advancing breakthrough research, celebrating scientists and generating excitement about the pursuit of science as a career.

The next generation of scientists, like the current, is suppose to strive for science that is exciting at the fame and fortune level. The boring details of daily lab work will not get you this prize. The boring narrative of a failed experiment or failed idea will not get you the $3M. It must be exciting, breakthrough and worthy of an award, as decided by others who pursued and won the prize. You must be one of them. In terms laid out from The Amgen Study, you must tell "the best story".

According to the Begley, Ellis paper in Nature:

Some non-reproducible preclinical papers had spawned an entire field, with hundreds of secondary publications that expanded on elements of the original observation, but did not actually seek to confirm or falsify its fundamental basis. More troubling, some of the research has triggered a series of clinical studies — suggesting that many patients had subjected themselves to a trial of a regimen or agent that probably wouldn't work.

This is the kind of research that wins awards unfortunately. If you can spawn an entire field, people are going to take notice. It is known in the scientific community that you can spawn an entire field with a good story, not necessarily good science.

You will not see an award for people who sacrifice their own careers by retracting papers when necessary. You won't see whistle blowers get an award for jeopardizing their careers for the best interest of science. There is no award for "Most Reproducible" or "Best Designed Experiment".
As pointed out in the Begley, Eliis study:
In studies for which findings could be reproduced, authors had paid close attention to controls, reagents, investigator bias and describing the complete data set. For results that could not be reproduced, however, data were not routinely analysed by investigators blinded to the experimental versus control groups. Investigators frequently presented the results of one experiment, such as a single Western-blot analysis. They sometimes said they presented specific experiments that supported their underlying hypothesis, but that were not reflective of the entire data set. There are no guidelines that require all data sets to be reported in a paper; often, original data are removed during the peer review and publication process.
Scientific research that is reproducible, where authors pay close attention to controls and their own biases, is not part of the criteria for a publication, promotion or an award. It is good for your science but it is also a risk. What if your work is not reproducible, as was the case in 90% of the papers looked into by the Begley and Ellis in the Amgen Study? As we learned, nothing will happen. You can still get published, promoted and awarded a prize.

Therein is where we need to see a prize. Take $33M and set up a laboratory where a group of scientists accept "nominations". If you think you've got something that can stand the rigors of another group of scientists looking to poke holes in your theories and evidence, throw your name into the hat. The judges will judge based on communication of ideas, transfer of science, reproducibility and for potential. It is not important what a group of rich kids from Silicon Valley think of your narrative. That is only a story selected on a political level by award committee and their awardees. Something greater than them is happening in science and they are not worthy take interject themselves into this world with another million dollar prize. If only they would use the money for the good of everyone in science and set up a Begley/Ellis-like organization. Select 50 papers to test each year. Award those that are reproducible. Give booby prizes to those that are not.