Reveal, Reclaim, Reform The 3 R's in Modern Science

On the blog front, I have been suffering from a bit of paralysis.  My intent for this blog is to focus on my field of interest: transcription, transcription regulation, and transcriptomics. However, my focus has been diffuse and scattered lately.  In the past few weeks, I have been caught off guard by the number of bloggers, columnists, and science writers who have been critical of the waste, fraud, and misconduct in science. 

Let me clarify: I am not taken back by the comments that have been made.  Instead, I am surprised to see more scientists be open about what is happening in academic science.  In the past 4-5 years, when I openly expressed my concerns about the state of academic science, I was accused of not being a team player or worse, not being competitive.  Seemingly, by pointing out the failings of academic science, I was seen as someone who could no longer compete with my peers.  The hesitation to be as corrupt as my competitors suggested I was not a strong scientist. 

What troubles me most is how my silence enabled continued misconduct.  Now I feel compelled to share my experiences and support those who dare to challenge the status quo.  It is time to “reveal” the bad behavior of scientists so that collectively we can decide how to recognize and discourage underhanded behavior.

Misconduct is not a new problem, thus pointing my finger at individual scientists is hardly productive.  Instead, I want to speak up to say misconduct, whether deliberate or careless, gender and ethnic disparity in career advancement and funding, as well as exploitation of students, technicians, and postdocs are all important topics that should no longer be ignored.  I witnessed this behavior at every level of my training from undergraduate to project scientist.  Like most trainees, I tried to steer clear of those who were blatant frauds, but eventually ended up in an area where inappropriate behavior was considered smart and competitive.

During my second postdoc, I was surprised by the number of graduate students and postdocs who could relate multiple, unique, and individual stories of scientific misconduct by their PIs, collaborators, or lab mates.  Worse, I met a number of newly minted (and inbred) postdocs who supported underhanded approaches to double salaries, honorary authorship, and un-reproducible results.  Their objective was to increase authorship and grant funding.  I encountered the attitude that most of our work is obsolete in 5 years, so why worry about the integrity of science? Keep your head down and worry about the paycheck and the number of publications on your CV, it is the only way up the career ladder.

Initially, I was outraged.  When I witnessed a postdoc who sabotaged the research going on around her, I encouraged one of the victims to speak up.  To my disgust, the victim was reprimanded and later fired, for revealing a problem in the lab.  The saboteur was rewarded for being competitive and given a raise.  The rest of the lab was told to never speak up again, as it will not be tolerated.  It was then that I felt defeated.  Once again, the whistle blower was punished.

Scientific misconduct is most insidious when it is from a person of power, who controls references, publications, grant and paper reviews.  As a result, we cannot put all of the responsibility on those who have been victimized.  However, this power is reduced when their misconduct is revealed.  As members of the scientific community, it is our responsibility to speak up for those who do not have voices.  Of course, keep in mind that graduate students have a department chair, and committee members to look out for them.  Technicians, undergraduates, postdocs, and senior scientists do not have this type of support under our current system, where the University has a vested interest in the PI’s career rather than the careers of those in the lab. 

We need to “reclaim” our voices, expertise, and experiences.  Too many postdocs leave their field of research taking with them all of the knowledge they amassed from undergrad to postdoc.  As a result, experiments are never published, shared, or further explored.  What a waste of time and effort.  How do we capitalize on this obviously untapped source of knowledge? Macro or micro-blogging coupled with open-notebooks or mandatory raw data sharing is probably the best way to establish an area of expertise. 

A little chatter about the relative levels of scientific integrity at different Universities, departments, and lab groups should be expected.  I know this makes some people uncomfortable, but our silence only aids the misdeeds of others.  We should have a greater fear of tarnishing our reputations than fear of not getting funding.  We should have greater pride in publishing sound, reproducible data than pride in a mega-paper in Science, Nature, or Cell.  

I challenge everyone who became a scientist to satisfy curiosity and to advance a particular scientific question to reclaim positions as mentors, investigators, and experts.  Grant funding and academic positions are very slim for early career investigators, but that does not mean we must stop being scientists.  There are other outlets, including using social media to advance a scientific question.  We may not have the means to perform experimentation, but we can read, evaluate, and question the published work of those in our fields.  Ultimately, to blog, tweet, and comment our critiques of the work is the best type of peer review, as it gives us the opportunity to have on-going conversations about the science.  In doing so, we will reveal who among the authors understood the experimentation and experimental question from those who were mere middle-managers, assembling the story.  Our voices are the strongest tools we have to work against the rise in scientific fluff, particularly un-reproducible or highly improbable research. 

Better yet, as outside voices, we can champion good science, even if it is not published in a top-tier journal.   Good science should be publically acknowledged, and social media provides an excellent platform.  Furthermore, social media is a platform that provides all of us the opportunity to establish an expertise in a field of study.  Ultimately, using our voices to share our knowledge is the best way to “reform” science, as we know it.  

What is your passion?

Do you know what you want to do the rest of your life?  I do.  I want to be a working scientist.  Better yet, I want to be a productive scientist, meaning that I want to contribute good science and good training for the betterment of my field of study.  I really do not care if the science is published in a glam journal, as long as the data is accessible.  I do not care where I do the work, as long as I can provide for my family.  

Like any postdoc or senior scientist, I have taken time to prepare job applications for tenure track positions, or even lecture positions.  I have gone through the process a couple of times, but fell short of a faculty position.  This is disappointing, but there is an odd sense of security in the realization that most of my former co-workers are not in faculty positions.  Some realized that they were not willing to move to another city or state, others just grew tired of the time spent marketing themselves.  Like myself, they hated giving up the time needed to look for a job, when there are so many experiments left to do.  

My friends who have found positions, have done so with a price.  Either they moved to cities that were less desirable, or took a position that offered less salary, bench space, and/or more teaching than they really expected.  I am proud of them for their sacrifices.  Unfortunately, I have reached a point in my life where the family's happiness is more important than my title.  I can no longer move from city to city chasing a tenure track position that will likely never happen for me.  

Does this mean I have given up? No.....it means that I have changed my focus.  For years I believed that my only options were industry or academia.  But I now see there are many more options that scientists do not consider, including freelance, consulting, and commercialization.  Another option is to be independent, really independent.  No academic affiliation, no industrial application.  The appeal is the freedom.  The fear is the lack of a safety net, which includes retirement, health insurance, and a dependable salary.  

A few people have been public in their independent pursuit, including the Perlstein and the Leto Labs.  Perlstein has trumpeted crowdsourcing as a way to fund his research, while Leto's motto, as taken from his website: "We fund ourselves, so that we do not have to worry about being ignored or constrained by those who do".  I am certain there are other independents, who fashion an approach that works for them.  In fact, I think the independents have always been around, just largely ignored.  

I will stress that I plan to do something a little different.  I want to provide a PATH for other independent scientists.  My personal struggle to create an independent, productive lab is not interesting enough unless I help the future independents.  It is time to provide reasonable competition to the current academic model.  I predict that a new wave of independent scientists are coming.

A Visit to the Home Lab

I spent Friday night with old friends (and a few new) at the Fred Hutchinson Cancer Research Center.  Friday evenings are generally celebrated with a beer hour to discuss science (or more often--weekend plans to hike, kayak, or ferry somewhere in the beautiful Pacific Northwest).  Each week, as different lab hosts the beer hour with a keg or two of beer and some yummy snacks.  But the highlight for each beer night is the poster that the host lab puts up to announce their intentions.  My good friend Steph in Adam Geballe's lab is the master at these posters.  My favorite is when she photoshopped Adam's head to Psy's for a Gangnam style Hutch beer hour.  But she really topped herself with a "3D poster", which was basically a bust of Adam on a "keg" pedestal.  This bust is now called the "Geballus", hopefully it will be awarded internally to other labs when they do something GREAT, like an outstanding lab halloween costume theme or spirited Christmas decorations.

It is silly fun, I know.  How could this possibly be important in the grand scheme of things?  Well, it is a morale builder.  It is a safe place to discuss the week-to-week, day-to-day trivia of life at the Hutch.  I have solved many experimental problems after discussion with other talented postdocs or faculty.  This is a place where science is the focal point of the day and night.  The Hutch is large enough to have research diversity, but small enough for most people to know one another.  Graduate students and Postdocs come and go, but they typically leave reluctantly.  Is everyone happy at the Hutch?  Probably not.  But I do not recall many people who were eager to leave the place, as it is truly an inspiring place to work.  If anything, I am one of the people who complained the most, about someone with whom I worked.  

I did not feel a similar magic when I moved to UW in 2008 or UCSD in 2009.  In fact, I met many postdocs at UCSD (2009-2013) who were far more unhappy than I was.  The competition for grants, papers, and their PI's attention seemed too great for most postdocs to remember the joy of science.  This is why I left.  This is why I took a job that on the surface does not seem to be the type of job that will help me get to my career or science goal.  (My gut still says it was the right decision.)  

The benefit of my current position is that I am close to my Postdoc "home", The Hutch.  I feel a little more centered having made a visit to the campus and spoken with the great scientists who stopped by the beer hour for a little conversation.  I am ruminating a number of things that I want to do for my current project, that I need to do for the previous project, and that I hope to do for a future project.

I wonder....is it the independent spirit of the Hutch that makes it magical?  

Lead or Follow?

The twitter feed for many of the people I follow is often filled with critique of other scientists.  Typically, the tweets are critical of the process of science, with a little self-rightous tone.  Nothing that I take too seriously, but I know there is an underlying reality to the criticism.  From where I stand now, as there is a conflict between my early training (undergrad and graduate school) and my later senior postdoc experiences.  Much of the conflict has to do with scientific integrity, reproducibility, and authorship.

When I was an early post-doc, one of my dual mentors warned me about sharks in the water.  "Learn to swim with them while you are a fish" my mentor would say, "but do not trust them not to eat you".  I resisted this advice early on, not wanting to be distrustful of my fellow scientists.  After all, our efforts at the bench speak for themselves. But it seems that our field has bottomed out in integrity.  I am not certain that we value bench work.  Instead, we reward the project manager approach, where a theorist gleans the experimentation in the lab, department, university, or field of study.

When experimentation is undervalued relative to interpretation, we lose the fundamental aspect of research, namely "observation".  Very little space is allocated to experimental methods in many high impact journals.  Details are very brief and reagents are hard to track.  Worse yet, in silico data is harder to track when much of the bioinformatics are in-house and code is guarded closely.  How can we advance a field of study without discussing the methods used?  How did we get to this place is science?  Is experimentation a dirty word or did we become so adept at incorporating so many small projects into one big paper that we lost sight of the individual experiment?

The knee jerk reaction is to have journals, such as Nature, define policy.  But I think the bigger issue is the lack of outrage by all of us in the field.  If we want reproducible science from our peers, we need to expect reproducible science from our peers.  This means we need to ask for the details when we review papers, attend meetings, and collaborate.  We need to take pride in the details rather than hide behind reputation and big stories.  When a researcher replies that the experimental method is unimportant, we need to be suspicious that the researcher either does not know the details (thus is actually a project manager not the experimentalist) or is hiding something.  We also need to demonstrate good science when we publish our own data.

Lead by example and the field will follow!

Transcriptomics

Over the past decade, I have been trying to identify some of the most difficult transcripts, such as the antisense transcripts at the FRM1 (asFMR1) and the Ataxin-7 (SCAANT1) loci [HMG, 2007, 16(24), Neuron, 2011 70(6)].  What is so challenging about these transcripts is the sequence.  Each contain repetitive CGG and CAG regions, respectively.  However, the biggest challenge has come from the scientific community, which has and absolute aversion to antisense transcripts, bidirectional transcription, and many noncoding RNAs.

I have read or heard every possible argument as to why these transcripts are unimportant.  Yet, more and more groups are finding noncoding or seemingly noncoding transcripts.  I have faith that we will eventually have a clear picture of the transcriptome, but the persistent wading through the muck is slowing down progress.  I have to ask my scientific peers, why be a road block?  At the end of the day, does it make you feel better about your scientific progress to block the progress of others?  Or do you hold so dearly the central Dogma DNA->RNA->Protein that you cannot imagine what else is happening in the cell?

Greater than 90% of the human genome is transcribed, at some point in time.  The validity of this observation seems to be one of the hardest to convince non-RNA biologists.  There seems to be a disconnect in understanding how our genomic sequence.  I am always surprised that there are highly educated scientists who would rather believe that the majority of our genome is nonfunctional, or better yet, unimportant.  Yet, we evolved to carry this much genetic information.  Of course, I have heard many a technician exclaim that we have not evolved enough, but that is for another day.  Instead, I will post one of my favorite figures from a fairly recent publication.  Here we see an updated view of the activity at a single gene locus. So much effort from so many research groups!  And I know the hurdles faced by all of us to get this information to the masses.  If only our "peers" could have had more open minds, we could be further along.