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Thursday, August 29, 2013

I Am... a Research Laboratory Scientist

I recently watched the documentary, "I Am". In this documentary, Tom Shadyac, a very wealthy and successful Hollywood director (Ace Ventura, The Nutty Professor, Bruce Almighty) gives away most of his wealth to live a more simple and meaningful life. He gives up the private jets to fly coach. He sells his real estate in exchange for a modest trailer in North Malibu. This new path in life leads him to make this documentary. He asks two questions:

What is wrong with our world?
What can we do to fix it?

We need to ask the same questions of science.

What is wrong with science? Like any human enterprise, we have good, bad, and ugly. In science however, the good is so goddamn good that the bad and the ugly are cloaked in an aura of success. As Mark Twain said, "Give a man a reputation as an early riser and he can sleep til noon." In science we have people taking advantage of the good reputation. We have gone so far over the deep end that people argue against orchestrated efforts to make science more reproducible. Reproducible useful science that can be turned into a technology is somehow not of interest to all modern day scientists. It is now a special niche for online groups like this one.

What can we do to fix it?

The first thing we must do is admit that we are fallible. We have our share of negative things. We have begun to see more policing of the journals, thanks to the internet and concerned citizens of the scientific community. They seek the negative and shine a light on it. "Watch out! Don't step on this." We have Retraction Watch for example, which deals with a side of science publications the editors would rather not acknowledge. Not everything that gets published is true. In fact, being truthful is not the main concern of the journals. They want that wow factor. But the negative is a necessary side of life. Without pain we won't know pleasure. Without rainy days we won't appreciate the sunny days quite as much. Why then are the journals full of so many positive outcome research projects that had no apparent unexplainable results?

There must first be an acknowledgment that something is wrong before we can begin to make corrections. In this retraction reported on Retraction Watch we have a George Washington University professor being policed by anonymous "peers" on another useful website called PubPeer.  Rakesh Kumar (no blood relation to Kumare... but there is a relationship) retracted a JBC paper after being called out for some obvious manipulations and reuses of photographs taken of fluorescent stained cells.
Fig. 8 of this paper shows image of fluorescent cells. The top panel of 8B (Ctrl.) and the lower left panel of Fig. 8D (MCF-7/MTA1, Ctrl. siRNA) has part of the same image used to represent a completely different experimental condition.
Furthermore, the top right panel of Figure 8D (MCF-7/pcDNA, HMMR overexpression) contains portions of an image from another paper by this group (Figure 7C, top right panel of JBC 2012; 287: p5615-5626, PMID: 22184113). The panel below this (lower right of 8D) also contains part of the image from the lower right portion of Fig. 7C in the other JBC paper. Identical images presented for completely unrelated experimental conditions.
Notably the images are not re-used “straight”, but are re-sized, different exposure, contrast, brightness, and moved slightly in the field of view. This makes it unlikely that this was simply an accidental pasting of the wrong image during manuscript preparation.
Finally, Fig. 8C of this paper shows cell migration (scratch wound) assays. Portions of the top right panel are again identical to images in the top right panel of Figure 7A in the other JBC paper.
The peer reviewers missed this and they always will. They do not have the tools to catch such errors/oversights/mistakes/misconduct/fraud. The people who catch this kind of misconduct are just nerds who don't want to compete in a rigged game. It brings them great pleasure to be a part of that great idea, that science is self correcting. Other groups are leveling the playing field via open access. Sometimes our science becomes too complex for one individual or one company to tackle alone. We have people increasing transparency through Open Access initiatives. Groups like:

Foundation for Open Access Statistics
The AllTrials Campaign

... to name a few.

In the documentary Tom Shadyac speaks of insanity. His version of insanity is where we take more than we need and knowing that the group would be better off if we shared. The analogy in "I Am" is a tribe that lives for 1,000 years working together. Everyone has a role. Some require more strength, like the hunters. Some require more caring, like those who look after the children and the elderly. One day the strongest hunter decides he is doing the most important work so he begins to store his kills up in a cave. Soon the strongest of the tribe begin to hoard more and more rewards earned by their hard labor. We have this in science. Our strongest scientist get the most money. They conduct their research and only release the details as they see fit. There is no system to do make the scientist share information. To end this insanity, we have to make systematic changes. Asking powerful individuals to simply share more is not going to work.

Another example of insanity is doing the same thing over and over expecting different results. Over and over we give the power to the same group and we keep the weakest group, the laboratory workers, worried about their jobs if the wrong kinds of results show up. How would you create a more productive balance between the PI and the lab?

The next thing we must do is go to the positive side of our work. Science is power. Knowledge is power. A well trained, certified laboratory workforce is what I would do to fix the world of science. If I were to design a course of study for a one year certification for research laboratory scientists (RLS), what would it look like? Design of Experiment, Quantitative analysis, Imaging, Technical Transfers/Writing, Process Development... The simple act of thinking up a training course gets ones mind thinking about what matters in research. After the initial training and certification an ongoing lifelong education would begin. Level I, Level II, Greenbelt, Blackbelt... An empowered laboratory workforce would indeed be a thorn in the side of likes of Rakesh Kumar. To those who care a little more about science and the rewards it provides, it will increase the value of research dollars.

One day you will be mistaken for a 1990s, 2000s style research associate, post doc, research assistant, lab tech...  Weak, easily manipulated and easily blamed for mistakes. Hopefully you will be able to respond, I Am a Research Laboratory Scientist (RLS), and it means something.

Saturday, August 24, 2013

Fred Astaire and Merck

"Can't sing. Can't act. Slightly bald. Can dance a little."

This was note written by an RKO executive after watching a screen test of Fred Astaire. Fred went on to do pretty well for himself. He contributed to the best years of MGM Studios. Later the studio fell from grace proving that success can be a fleeting thing. The documentary, "That's Entertainment" has some very interesting before and after footage of MGMs rise and fall. Fred Astaire narrates his segment from a run down backlot set where he had filmed The Bandwagon. MGM was in trouble financially and selling off the backlot. "That's Entertainment" was the last major production filmed there.

I like to compare Hollywood to the biopharma business because they have a similar perilous existence. A blockbuster movie or drug can bring in a lot of money creating the illusion that what you are currently producing is a part of your success. What a studio and a drug company must alway have is a pipeline of new products that will generate that next blockbuster. Once you've got your blockbuster, there is a window of peak earning. When the earning slows to a trickle, you look towards the pipeline. The pipeline is nurtured by the guys who say things like, "Can't sing, can't act..."

The job of nurturing the next big thing is tough. There is no road map. The last big thing doesn't always tell you what will work next time around. There is always the prospect that you could fall just like MGM, once the most powerful studios in all of Hollywood. Which brings me to Merck. How much trouble are they in?

In 2011 they began layoff off people to reach the goal of 13,000 less employees. Any Fred Astaires in that group? Then we get this report suggesting further cuts.

As pressure builds on MRK mgmt to: (1) improve R&D productivity, (2) maintain top-tier operating margins, and (3) continue returning cash to shareholders, we believe a deep restructuring should be seriously considered in light of the relatively lackluster 2013 top-line performance, disappointing Ph III/ registrational pipeline evolution (odanacatib, suvorexant, Bridion U.S.), and overall industry challenges. We estimate that every $1B reduction of operating expenses would add $0.25/share to MRK's bottom line

As one commenter said on the Forbes website:
Wrong! Investment in R&D now means profitability in 5 to 10 years. If Merck has a lackluster performance now its because they listened to this sort of “advice” in the last decade. It makes no sense for the company – slow suicide so Wall St can make an extra buck.
This is quite clear to those of us with an interest in the science, not the financial spreadsheets. As George W. Merck said, "We never try to forget medicine is for the people. It is not for the profits. The profits follow, and if we remembered that, they have never failed to appear. The better we have remembered it, the larger they have been." Good medicine comes from good science. You have to remember how this science works. It takes many years from start to finish. Often times the finish is disappointing. To divest in the process because of the current lot of disappointments is a misunderstanding of timeline of this science. 

Sunday, August 18, 2013

Blue Collar Scientists

In biopharma, the PhD is the white collar worker. The laboratory worker is the blue collar worker. There are also administrative, regulatory, statistics and various other people, but what I want to focus on here is the science. Who does it? What is their role in developing a new drug? What do they know about the disease for which they are developing drugs?

In science we have the hypothesis to begin our work. A hypothesis is a testable statement based on accepted grounds. Contrast hypothesis with conjecture. Conjecture is an unproven proposition, often times mistaken as fact (or hypothesis) by an unscientific (Cargo Cult) mind. The first thing to note here today, on this concept of white and blue collar scientists, is the role hypothesis and conjecture play in the two disparate occupations.

The white collar worker swims in a sea of conjecture. The New Coca Cola recipe, for example, was developed because white collar workers decided that people wanted a better Coke. The sales proved them wrong. In science, we start on solid ground with the hypothesis and push the idea forward as directed by what we find. Penicillin, for example, was found in the laboratory by accident. From Wikipedia:
Fleming recounted that the date of his discovery of penicillin was on the morning of Friday, September 28, 1928.[19] It was a fortuitous accident: in his laboratory in the basement of St. Mary's Hospital in London (now part of Imperial College), Fleming noticed a Petri dish containing Staphylococcus plate culture he mistakenly left open, was contaminated by blue-green mould, which formed a visible growth. There was a halo of inhibited bacterial growth around the mould. Fleming concluded the mould released a substance that repressed the growth and lysing the bacteria. He grew a pure culture and discovered it was a Penicillium mould, now known to be Penicillium notatum
Here we have a biotechnology project that is the antithesis of New Coke. There was a good reason to start the project. The anti-bacterial effect of the Penicillium mould was already known, dating back to the 1870s. Back before big business science projects were funded to the tune of billions of dollars per year, scientists had to make observations on their own. This observation is in the realm of blue collar work. It took years and years of blue and white collar work to make penicillin what it is today, but it all began with an observation.

Not many white collar workers of the caliber of Alexander Flemming. How many biotech/pharma executives would walk into the laboratory and make observations? The Nobel Prize winning scientist I worked for had his picture taken in a white lab coat sitting by a hood with a bunson burner lit up in the back ground. We hung the picture in the lab with the caption, "This isn't like my piano at home." We put it in the lab so he wouldn't see it and get angry.

The identification of Alexander Flemming caliber talent would be difficult to do considering laboratory observations are not part of the white collar scientists job description. The discovery scientists we wish for are neither blue nor white collar. They are pure scientists who require a large support network of both blue and white collared workers. Flemming didn't single handedly send penicillin out to the world from that lab where he first saw the mould fighting off the germs.

We can see that there was a long path taken to place penicillin in the world of modern medicine. With this in mind, let's examine the modern world of blue collar science. Undoubtedly there were many hospital laboratory technicians as well as biotechnology laboratory workers who contributed to the penicillin effort.

If you are looking for a transition from the biotech lab, you might want to look at the field of Medical Laboratory Science (MLS). In order to take on this work you must have a Bachelors degree with specific math and science coursework. If you graduated more than 7 years prior you must go back and take a senior level chemistry and microbiology class plus lab. You'll need three formal references, the forms to be filled out are provided by the school. You fork over $50 and apply. The school selects candidates in for interviews. Once selected you will embark on a one year $20K education involving senior level courses in clinical lab skills, intro to clinical lab practice, chemistry, clinical chemistry, micro I and II, clinical microbiology, parasitology, mycology, hematology, serology, immunology and molecular diagnostics. After the year of education you must take and pass the MLS exam to become certified. Now you can begin applying for a lab job down at the hospital.

Let's compare the requirements for a typical laboratory job in biotechnology:

Research Associate/Senior Research Associate - Target Validation - Seattle Genetics 

The successful candidate will:
• Design, conduct, and interpret experiments utilizing a diverse array of techniques aimed at validating early targets in Seattle Genetic’s drug discovery pipeline. 
• Standard target validation methodologies will include flow cytometry, cytotoxicity assays, and immunohistochemistry. 
• Additional techniques will include cell-based assay development, cDNA/RNAi transfection, qPCR, RNA/DNA purification, Western blotting, protein-protein binding assays, and epitope mapping. 
• There will also be direct involvement in the discovery/development of predictive biomarkers.
• The successful candidate will prepare for and present their result at departmental and integrated project team meetings.

• BA/BS with 8+ years or MS and 5+ years of experience in the biotech/pharmaceutical industry
• Significant training/experience in Oncology, Biochemistry/Pharmacology
• Experience with physical and functional genomic screening is a plus
• Experience with high throughput robotics is a plus
• Experience with biologic therapeutics is a plus
• Experience in predictive biomarker discovery is a plus
• Excellent interpersonal skills
• Excellent presentation skills

You will not need any certifications, just the ability to convince the hiring manager that you have the skills to do the job. You should also believe that the hiring manager can do all of this him/herself, but due to white collar duties, they don't have the time. The two of you will be on the same page at all times and always move on to the next logical step. 

Notice the first objective; to validate their targets. One would think they have already done that, thus the targets have become theirs. Why would someone outside of the organization have to come in at the blue collar level and validate their targets? Also note the very first word, "Design"... experiments. Have they blurred the line between PhD and laboratory work? 

Alas, the biotechnology blue collar worker has a lot to do. The medical laboratory worker must compete for the higher education that lead to hospital blue collar work. Maybe not as blue as the janitors but still... they aren't the doctors.  The MLS performs standardized tests. They report everything they do. The biotech research associate on the other hand, has only a college degree. A degree in biology is the same as biochemistry. Both are vocational diplomas for entry level biotech or prerequisites for the MLS program. There is no formal training in research. They report most things they do to the white collar worker, but not to a regulatory agency. Somewhere along the line the research associate (RA) must pick up "significant training/experience in Oncology", AND ROBOTOTICS! And in contrast to the Steve Jobs concept that difficult personalities can sometimes be the most creative, you must finish off your skill set with an agreeable personality (excellent interpersonal skills). 

It is too much to ask but the Seattle Genetics job description is par for the course in the pharmaceutical industry. The white collar workers design these job descriptions based on conjecture. The perfect worker to develop drugs operates somewhere between white collar scientist, Alexander Flemming scientist, and laboratory technician. Modern day biopharma white collar workers want to wrap up all of the talents and skills that went into developing penicillin as a medicine, and create one blue collar lab worker. Note also the timeline from Flemmings 1928 observation to the widespread use in penicillin in WWII (1940s). The Seattle Genetics RA won't have 15 to 20 years to accomplish the oversimplified goals, i.e. validate the companies drug targets. They may get up to 10 years maximum, if they have excellent interpersonal skills. 

Like the lemming who runs to the sea and jumps off the cliff to certain death, the RA will take on the job, prepared to do whatever they can to validate the companies drug targets. They may feel that they are lemmings facing the mass suicide but times are tough and they didn't get the white collar credentials before entering the world force. They must do their part and live year to year not knowing when the end is near.

I can envision a future where the laboratory workers in biotechnology must also go through a similar additional education as the Medical Laboratory Scientist. To gain respectability, this class of worker must somehow unite and form their own certifications and specialties. How do you convince Seattle Genetics that you have Oncology training/experience? Actually go out and get it. Make yourself useful and make the people you pay for the education market their product. Best of all, make the white collar scientist less authoritative over the laboratory and thus over reality. This newly empowered laboratory class will cease to operate like the current lot of blue collar lemmings. They may even operate separately from biopharma. Science does not really need the blue collar mentality. Not all work is equal but ultimately, we can all think and observe. We can all be practice science somehow. 

Thursday, August 15, 2013

Another One Bites the Dust

In my last post I wrote about the demise of VLST and the majority of other companies started at Accelerator and how no one was invited to their funeral. The local news organizations do not see fit to report on this kind of news. When a new company begins there is a sense of joy and hope for a brighter future. More companies means more jobs and that should snowball into a major biotech hub in Seattle. We hope we are not witnessing more foolish investments akin to the dot com era. Perhaps we just have a preference for good news. In order to truly experience reality however, you have to acknowledge bad news as well.

The latest silent departure is Marina Biotech. Long ago they were known as Nastech and ruled over by a mean old man named Steven Quay. He terrorized his secretaries, subjected his scientific staff to pop quizes in freshmen chemistry, and organized an entire days worth of work for several high and low ranking admin people to ensure that he never ever again ran out of Equal in the breakroom. He turned hundreds of millions of dollars of investor money into... several millions of dollars. He made Jim Cramer of Mad Money look like a fool for recommending Nastech, prompting Cramer to issue an apology to his followers. When the final curtain was about to fall Quay gave his usual quarterly report, "All is well, just keep giving us money. Big plans in the works folks..." To which one major investor responded, "Quite frankly, we don't believe you anymore."

Don't worry folks, if you still want in on a Quay company, here you go.

Yesterday it was announced that the remnants of this multi hundred million dollar mistake is leaving town. Marina Biotech According to the RNAi Therapeutics Blog:

Financial details of the transaction were not disclosed.  Through the assignment of the patents, Arcturus stands to collect the milestone and royalty streams from Marina’s existing licensees.  This includes Tekmira which in its quarterly filing disclosed this week that it would have to pay $3,250,000 in milestones plus single-digit royalties for the technology.  Although these numbers pale in comparison to what Alnylam has asked for RNAi trigger licenses in the past, this suggests that the undisclosed financials and likely upfront payment by Arcturus should have been substantial for a company like Marina…at least enough to continue to pay its patent prosecution and other bills. 
How Arcturus paid for it is unclear to me given that its first significant capital raise involved merely $1.3M.   
It's not clear to me what is left of Marina to move to MA. Xconomy reported the end of day to day operations in June 2012, The Seattle Times reported in August of 2012 that Marina slashed board members down to 3. The news of their death rattle here in Seattle ends there. Like VLST, Marina Biotech ceased to be, at least in our new world of cyber media. Micheal French, President and CEO of Marina has resurfaced in the media on the east coast. The Boston Business Journal picked up the story. Marketwire got the story. Xconomy Seattle, The Seattle PI, and the Seattle Times have yet to mention this little story. Michael French, releaser of press, is proud to announce his arrival in Boston, not so much his departure in Seattle.
“The Arcturus deal along with the extension of our secured note provides us additional runway to pursue both collaboration transactions and financing opportunities in order to fund our operations and advance our clinical and preclinical programs,” French added.
Why focus on the past?  We here at the CCS tend to think that the past is important. It is not likely that the hundreds of millions of dollars and ten years of research at Nastech/Marina was all wasted. It is more likely that no matter how hard they tried, they just couldn't hammer that square peg through the round hole. Over time, people became tired of throwing money into the projects. The scientific staff, the most experienced human beings on the planet with Marina technology, were sacked over a year ago. It's not as though the talent pool in Boston was the missing link. And if it was, how on earth did the geniuses at Nastech originate something that only Boston scientists can finish? A collaboration between scientists who have never and will never meet for one single conversation?

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.
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 explicitly say what this is, but just
hope that you catch on by all the examples of scientific

This little Cargo Cult company can show up in a new town with a new plan, but they have the same old crap they left town with. The same old crap that was known as Nastech/Marina Biotech. Xconomy and the Seattle newspapers can ignore it but another one has bit the dust. What will this town look like in ten years?

Monday, August 12, 2013

If a Biotech Falls In Seattle...

The Accelerator Corporation recently saw one of their graduates, VLST, fail. Two months later, Xconomy, local "news agency" on the technology world in Seattle picked up on the story. The question here today is why those $50M biotech trees falling are not heard in the forest of Seattle business reporting.

In 2009 the Seattle PI shut down newspaper operations. Most of the reporting staff went away. This was a tragedy. Newspaper reporters wandering around town looking for something interesting to write about was perhaps an old way of living. Herb Caen created a 60 year portrait of daily San Francisco life. Mike Royko in Chicago was an irritant to local politicians. While the Seattle PI did not have such a character as Caen or Royko, they had people with just as much interest in their local scene. It would be hard to imagine the PI missing a story such as a local $50M biotechnology company, in the heart of the Paul Allen "build it and they will come" biotech corridor crashing and burning. The Seattle Times??? In my Utopian world, a Caen/Royko type reporter sits at the BBQ joint around the corner from VLST eavesdropping on the table behind his seat at the bar. They're talking about losing their jobs. This is important to the local reporter. Jobs mean news. Psssst. Someone slips a napkin under his plate and walks away. "VLST is shutting down." The reporter has a story to chase after.

If there were such a reporter he would have had plenty of stories to chase after coming from the $212M fundraisers at the Accelerator Corp. If you check on their website, you won't find the fact that VLST has shut down. They only mention the $55M series B funding back in 2006. Look! Here is another viewpoint from a former Accelerator company founder, Johnny Stine of Spaltudaq (now Theraclone):

Try finding stories from the local Seattle news sources about the tankings or the MIAs.

Many times I feel like a nattering nabob of negativity with my approach to the biotech biz. Yet I have always known that the people running these companies were not planning on success. They were planning on making a profit somewhere between the press release on their successful financing and their eventual silent demise. As an investor or an employee, your contribution to their success will not serve you well in the long run. And the long run is where you must be invested. The cargo planes must land on your runway in order to be considered a success. The list here, taken from the Accelerator website and edited by Johnny Stine, ousted leader of Theraclone, is news. Would you invest in Accelerator? Would you send them a CV?

There is a much bigger story behind the VLST failure. There is the huge failure of the Accelerator Corp. Then there is a huge failure of the accelerator/incubator investment model. Then there is our system of succeeding without ever developing or selling a product. There is a story that presents a warning for our future. We can piece the story together and develop a model for success.

Friday, August 09, 2013

The FDA and Gilead

We all know that Donald Rumsfeld served as the Chairman of the Board for Gilead 1997 to 2001. He moved on to become the Secretary of Defense under GW Bush. The U.S. later purchased 80 million doses of Tamiflu after GW Bush warned the country that a minimum of 200,000 people would die from avian flu but it could be as bad as two million deaths. In fact less than 100 people have been suspected of dying from this strain of the flu. See "The Great Bird Flu Hoax" by Dr. Joseph Mercola for more info on this one.

Today however, we have to talk about the latest collaboration between our government and Gilead. I'm just going to cut and paste this off of Biospace. It is too unbelievable to try and edit down.

WASHINGTON--(BUSINESS WIRE)-- AIDS Healthcare Foundation (AHF) won a key legal victory today in a push for drug safety as well as increased government transparency when a federal court ruled that the Food and Drug Administration (FDA) illegally blocked Freedom of Information Act (FOIA) requests tendered by AHF regarding correspondence between the FDA and Gilead Sciences. The description of the documents in the court ruling also implies collusion, suggesting the FDA worked with Gilead on what to say to get their unfavorable drug trial results spun in such a way that the FDA deemed them sufficient to approve the drug for expanded use of Truvada as an HIV prevention pill for pre-exposure prophylaxis (PrEP) in uninfected individuals. 

Ruling for the United States District Court, Central District of California (CV 11-07925 MMM [JEMx]), Judge Margaret M. Morrow ordered the FDA to disclose “…complete and unredacted copies of documents…” and correspondence between the FDA and Gilead regarding the safety and efficacy of PrEP as well as the drug company’s application to the FDA for approval of the use of Truvada as PrEP. 

“This ruling confirms one of our deepest suspicions: the FDA colluded with Gilead to fast-track approval of Truvada as PrEP regardless of the results of clinical trials. Judge Morrow’s ruling suggests the FDA advised Gilead how to conceal unfavorable clinical trial results and coached them on what to say to get those unfavorable results spun in such a way that the FDA deemed them sufficient to approve the drug,” said Michael Weinstein, AIDS Healthcare Foundation President. “All the while, the FDA was illegally denying our FOIA requests on this issue. Today’s ruling is a huge victory for increased government transparency, and one which will hamper the government’s ability to withhold information about a drug’s safety and efficacy.” 

In September 2011, AHF filed a lawsuit against the FDA over its denial of several AHF Freedom of Information Act requests regarding correspondence between the FDA and Gilead Sciences regarding its potential application to expand the use of Truvada for use as a form of pre-exposure prophylaxis. Despite concerns and complaints from AHF and other advocates and the pending FOIA lawsuit, the FDA approved Gilead’s application for use of Truvada as PrEP on July 16, 2012. 

“While the FDA is supposed to act as a neutral entity, the court ruling today confirms the FDA had private discussions with Gilead, and even fought on Gilead's behalf to withhold documents submitted to them by Gilead,” said Tom Myers, General Counsel and Chief of Public Affairs for AIDS Healthcare Foundation (AHF). “The lack of neutrality shown by the FDA here is breathtaking—further underscored in recent years by the fact that the FDA's budget for drug approval is now directly paid for by pharmaceutical companies such as Gilead.” 

Judge Morrow’s ruling suggests that the FDA worked together with Gilead to conceal unfavorable clinical trial results and used the very narrow FOIA privileges to conceal negative information. Citing a declaration of David J. Pizzuti, Gilead’s Vice President of Regulatory Affairs, the Court noted: 

“Pizzuti also reports that Gilead and the FDA discussed what datasets Gilead would submit in support of the Truvada for PrEP applications.54 In addition, he states, Gilead had discussions with the FDA regarding other studies conducted with Truvada that contained unfavorable results.55 Gilead and the FDA discussed how the safety and efficacy data proffered with Gilead’s supplemental NDA was nonetheless sufficient to support approval.56 Pizzuti reports that these discussions were memorialized in correspondence withheld by the FDA under Exemption 4,57and that disclosing the discussions would reveal how challenging PrEP study results can be successfully addressed, enabling competitors to craft successful PrEP applications that will cause Gilead competitive harm in the PrEP market.


We don't know who in the government is twisting the arms of the FDA leadership to get Gileads products approved and sold, but Gilead certainly has had a friend or two in high places. This story should be enough for a serious congressional inquiry on who what when and where. Remember that the FDA was formed after a large number of children died from Sulfa drugs. Safety was the issue. Clearly todays leaders in the FDA have failed to do their job. As Tom Meyers said, "The lack of neutrality shown by the FDA here is breathtaking-further underscored in recent years by the fact that the FDA's budget for drug approval is now directly paid for by pharmaceutical companies such as Gilead." This is more than a judicial issue one would think. It is time for the legislative branch to find out what happened and why. 

From the Cargo Cult perspective, we have to focus on the cherry picking of data and how it is done at the highest levels. 
Judge Morrow’s ruling suggests the FDA advised Gilead how to conceal unfavorable clinical trial results and coached them on what to say to get those unfavorable results spun in such a way that the FDA deemed them sufficient to approve the drug,” said Michael Weinstein, AIDS Healthcare Foundation President. 
This takes us back to the Ben Goldacre initiative to increase transparency in clinical trials. If this isn't a good reason to push for such legislation I don't know what is. Not only do we need greater access to ALL clinical trial data to help doctors, scientists and patients make sound medical decisions, we need to know if the FDA is advising the pharmaceutical company on how to hide data!

Wednesday, August 07, 2013

Thermo Perkin VLST and Me

In my former life as a researcher for several biotech companies all up and down the west coast, I pumped a lot of other peoples money into high quality companies like Thermo Fisher Scientific and Perkin Elmer. These companies provide analytical instruments, reagents, antibodies chemicals, glassware, vials, pipettes balances, centrifuges, lab benches, bunson burners, software and so many wonderful things. If you really love nerdy science things, you want to work in a lab and you know these companies have PRODUCED over the years. Sadly, they are joining the layoff party. 655 people, 1.7% of the total workforce of Thermo, have been let go. 265 at Perkin Elmer will get their walking papers. That's 920 middle income jobs lost. Do we blame Obama for this one?

These are research related job losses. This this a canary in the coal mine. When money stops flowing into the biopharma businesses, circulation is cut down to just paying the C-level guys to "create value" from behind their Wizard of Oz curtains. The nerdy science world taking place in the laboratories goes silent. Workers go unemployed. No one is left to purchase the products sold by Perkin Elmer and Thermo.

Every research laboratory, large or small, academia or industry, uses these products. With the decrease in grant funding and massive industry layoffs, it's hard for Thermo and Perkin Elmer to find customers with purchasing powers. Here is an example of a lost customer from the Cargo Cults of Seattle. VLST lasted about nine years. They came out of Accelerator Corporation, a business incubator that funds ideas to the tune of a couple million dollars and a one year "proof of concept" period. They provide lab space, administrative help and leave the science up to the founders of the idea. Since 2003, when I the CCS arrived in Seattle, Accelerator has raised over $221 million. VLST burned through around $50 million in its nine year run. In September of 2012 they cut the scientific staff and redirected the flow of money into the hands of the C-level execs "creating value". Today we get word that they have been defunct since June! Marty Simonetti, CEO of the late VLST said he's been enjoying some time away from work during this beautiful summer in Seattle. "There were a lot of long days," he said, during his 7.5 year reign. 

Fifty million dollars is not a large pool of money for companies like Thermo and PerkinElmer to go to for sales. It is the accumulation of companies that have laboratories that leads to profit. Each failure is one less Thermo/PerkinElmer customer. It is up to the customer to use the Thermo/Perkin Elmer products properly and to advance their science into useful technologies. However, Thermo and PerkinElmer can lead these horses to the water but they can't make them drink. 

Most of these little Seattle biotechnology companies are staffed with the usual suspects, all early stage discovery trained scientists. As I have come to believe, they are masters at the narrative, but not very good at reproducible science. Non-reproducible science is vehemently defended by the career minded professional, but it is not useful in the world where science is to become a technology. And technology is right there in the  word, bioTECHNOLOGY. When you hand over $50M to the usual suspects they are going to do the same thing they did at the last company. They will defend their narrative just as they learned to defend their PhD thesis. They weren't taught how to make money from useful products while in the University. In Seattle, putting the usual suspects in charge of spending your money means, odds are, that you will lose your investment. Work for them and you will lose your job. Think independently and you will lose your sanity, if you understand the Cargo Cult speech.

Marty Simonetti is enjoying the summer off. "When the right opportunity comes along, I'll take a look at it." Thanks Marty, maybe your fellow Accelerator graduate Allozyne can use your asset liquidation skills.

The 920 people who lost their jobs at Thermo and PerkinElmer will join the unemployed, looking for the next job where STEM degrees are piling up. We somehow need to "create value" in ourselves. The Cargo Cults employ people who create value where none exists. In VLSTs nine years of trying, there were no clinical trials initiated from the "technology" advertised. They had to go and buy an antibody from the clearance rack at Pfizer. That too has been resold along with the "technology" that didn't work in the hands of VLST. What does this sort of value creation mean for the future of companies like Thermo and PerkinElmer, who provide the tools needed to do laboratory work? What does it mean for the 920 unemployed people at home with their PhDs, M.Sc. and B.Sc. sitting in a drawer collecting dust? Marty Simonetti is out there waiting for opportunities to take a look at. Accelerator is out there waiting to create the next VLST, using the usual suspects of Seattle and the same business model. Someday they may all get together again.

The next wave of biotechnology companies needs to focus on reproducible science. The unemployed include the usual suspects, like VLST execs and Accelerator dreamers.  But they also include skeptical curmudgeons like me. People who aren't looking to get rich quick. People who think reproducible science is less expensive than non-reproducible crap. People who have a passion for what they do. People who read Retraction Watch waiting for publications with their own names on them to come tumbling down! People who read Xconomy every day to keep abreast of the folly of our leaders. There is a system in place that has lead to an industry modeled on the University system, where our leaders are shaped. The model will get you published and it will get you early stage funding. It is not a system that leads to long term ever advancing science and technology.

I still feel that the Consumer Report of Science is a viable dream. There is a large pool of unemployed highly educated people with nothing to do all day but apply to Cargo Cult companies. The curmudgeons and skeptics need to come out of the dark and admit that they were only working for the paycheck. They can be useful, now, by reading the papers, analyzing the work and the conclusions. They need to be separated from fame and fortune, and made to feel an important part of something bigger than themselves. Like the un-named people who test drive cars and report on their findings in Consumer Report, an unemployed PhD can be anonymous and give an honest report on the latest oncology paper. The unemployed VLST laboratory worker should be able to discuss why they feel VLST took off like a $50M Led Zepplin. Imagine a place you can go on the  internet where you can read a thoughtful hones intelligent analysis of a paper you are interested in using for research. Imagine using the analysis to help you defend your research when it doesn't match the hoped for results. Scientists Unite!

Sunday, August 04, 2013

College Degree Bubble

The cost of an education has gone up and up while the value of a college degree has gone down. Is it the students or the University who is failing? Is it the world outside of the University, where the students must go that has misjudged the value of the education? There are many who provide the marketing for a college education. Hillary Clinton told the young people to get a degree and earn $1M more than those who don't. We all bought in and our society has become more and more educated. One would think we would all be well employed, dressed for dinner, attending the opera at night.

The college graduate becomes the student loan re-payer. Like the housing bubble, the college degree is a bubble. Bankruptcy does not do away with a student loan however. The housing bubble burst leaving many lives in ruins. But there was a pressure valve in the form of bailouts, foreclosures, short sales and so on. How will we measure the trouble we've sown in our education bubble?

In the housing crisis, we began to see an increase in prices. Investment money went into more and more developments. Many of those development left ghost towns of half finished condos and houses. A student without work experience is like a half finished building. Without something else to put on their resume, the college graduate stands about as much chance of finding a job as a the half finished ghost town has of finding residents. Although we can't see the college graduates troubles the way we can see the blight of an unfinished housing development, we should be able to see the effects on society someday. Remember that the real estate industry and Wall Street, most of the major players anyway, remained ignorant of the coming storm until it hit. When it hit, we all knew it.

Like the housing bubble, you could create tiers of debt holders that rank their ability to repay their loans. Engineering students get a high rank while art history majors get a low rank. What about our industry of biotech/pharma? Where do we fit in between engineers and artists? In this article, we see a bleak picture. Challenger Gray & Christmas calculated that 297,650 biopharma jobs were lost between 2000 and 2010, when consolidations and layoffs began reshaping the industry. Judging from that number, we must admit that the biopharma industry has failed to find the value in their college educated workforce. They have failed to train them to transition from college student to industry professionals. Some people see this problem from the opposite direction.

Unfortunately for industry, much of academia hasn’t responded to the change. “The Ph.D.s that are being trained at academic institutions are being trained to do discovery research. The amount of people you need these days to do basic R&D is so small,” adds Dr. Mintz, who follows biopharma employment news and trends as publisher of BioJobsBlog. “I think we’ve entered into a new world.”

It is this type of consideration, that academia is suppose to respond to industry demands, that contributes to the lack of value of a college degree. The University will put their students through the ringer, put them into heavy debt and send them out into the world with little help market their newfound skills. Hillary Clinton can sell the education to the student but who is selling the graduate to industry? Who is telling the world that a PhD who has been trained to do discovery research has a heightened ability to learn and adapt in high stress situations. All the industry needs to do is to standardize their needs, and provide university educated people with industry training.

“We need more scientists in development, people that understand pharmacokinetics, pharmacodynamics, toxicology, pharmacology, process development, process chemistry, biomanufacturing, those kinds of people,” Clifford S. Mintz, Ph.D., founder of BioInsights, a biopharmaceutical education and training organization, tells GEN.

BioInsights, by the way, is a full service bioscience training and career development company with expertise in medical communications and strategic management consulting. They offer training in a variety of areas including biobusiness, biomanufacturing, career development and job placement. The courses offered at BioInsights however are not unlike those offered in academia. Polymerase Chain Reaction for example, is taught in Biochem, Chem, Microbiology, Biology and on and on. There is little need to learn PCR over and over. There is a need however, to learn about and compare the latest options one has in PCR technologies. The industry needs regarding PCR should focus on management and selecting the most economic PCR system and how to apply quality management to making PCR work in the hands of young inexperienced laboratory technicians. The leadership needs to understand and train. Currently, the roles are reversed for most techniques performed in the lab. Junior lab workers often educate their leaders.

BioInsights has the right idea however. Industry needs a more specialized workforce. This however is the responsibility of industry. And here is the Cargo Cult angle today. Cargo Cults don't know why the airplanes aren't landing. Someone has to tell them and then tell them again and again until one day a true leader emerges and understands what they are being told. As long as industry and academia remain in bed together, trying to match educations to industry needs, we will continue to see college graduates working at Starbucks. 

At my last biotech job, the in-house scientists were banned from attending meetings with our contract manufacturing organization. Our small biotech in-house scientists were not qualified to effectively participate in the process development work. They were however, academia trained to speak up at meetings and make their presence known. After the CMO banned two individuals (PhDs) from attending the process development meetings, we in the small biotech did not get to learn from the CMO how they went about developing the methods that made our product! It was a huge educational opportunity that was lost. The moral of this story is that someone has to tell the Cargo Cults over and over again until they understand what they are missing. Those who wish to go from Cargo Cult to legitimate industry, have an entirely different education process to go through after they leave academia. Neither academia nor industry seems to know this yet.