Art On A Chip

Albert Folch from Lab on a Chip released a cool artsy project this past Friday that the journal has been working on. Defined bluntly, the project is a collaborative flickr account to share the pictures of your science.  The general theme is miniaturization, and of course dyed water on chips. The images already stored there are appealing to the eye and some are displayed below.

Droplet-scale estrogen assays in breast tissue, blood, and serum. A picture of the first microfluidic device (25 × 12.5 mm) applied to the extraction and quantification of estrogen in 1 l samples of breast tissue homogenate, whole blood and serum (Mais Jebrail, University of Toronto).

Cells on a micropallet array. Four 3T3 fibroblast cells are constrained to individual polymer pedestals (micropallets) on a glass substrate. Each micropallet can be released individually from the system using a high-powered laser (Nicholas Gunn, UC Irvine)

My only two real issues with the project are….

1) I wish I had thought of the idea. Although, if anyone is interested in making a more generic project along similar lines I’m game.

2) I have no idea how to add pictures to the “joint” flickr account! The announcement from Lab Chip, Introducing LOC: Art on a Chip, gave no instructions on how to do it. It isn’t like I’m totally naive with regards to technology, I have my own flickr account, I just don’t understand how one goes about adding pictures to someone else’s account. Check this post for an update when some nice person in the comments section finally explains the process to me, or when I find the magic button.

The Announcement: Introducing LOC: Art on a Chip

Mitch

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Something Deeply Wrong With Chemistry

An example of what is currently wrong with chemistry culture, even though it is dated.

Future chemistry faculty will have to be twice as smart, work with twice the efficiency, and reach the correct positions of influence if they want this type of unhealthy cultural attitudes to finally be put to rest. This is my goal at least.

Update 1: Guido Koch now.

Update 2: The underlying macroeconomic cause for why professors can get away with this behavior.

Update 3: This story has really struck a cord, thank you for sharing this link and supplying our first 20,000 visitor day!

Update 4: A transcribed letter from Robert Tjian

From now on, I or someone designated by me will take attendance at group meetings starting at 9:10 am. If you are not there, I will not sign your salary sheets. Also, if you haven’t noticed the number of people working on weekends and nights in the lab is the worst I’ve seen in my 17 years. The frequency of vacation, time taken off and other non-lab activities is bordering on the ridiculous. In case you forgot, the standard amount of time you are supposed to take is 2 weeks a year total, including Christmas. If there isn’t a substantial improvement in the next few months, I’ll have to think of some draconian measures to “motivate” you. I also want to say that the average lab citizenship and community spirit of keeping the lab in functioning order is at an all-time low. Few people seem to care about fixing broken equipment and making sure things in the lab run smoothly. If the lab were extremely productive and everyone was totally focused on their work, I might understand the slovenliness but productivity is abysmal and if we continue along this path we will surely reach mediocrity in no time.

Finally, those of you who are “lame ducks” because you have a job and are thinking of your own nibs, so long as you are here you are still full-fledged members of this lab, which means participating in all aspects of the lab (i.e. group meetings, Asilomar, postdoc seminars, etc.)

I realize that this memo won’t solve all the problems. so I am going to schedule a meeting with each one of you starting this Saturday and Sunday and continuing on weekends until I’ve had a chance to speak with everyone and to give you a formal evaluation. Sign up for an appointment time on the sheet outside my door.

This is the first time I’ve had to actually write a memo of this type and I hope
it’s the last time.

Robert Tjian

Update 5: Erick Carreira responds in an interview with Christopher Shea from The Boston Globe, vaguely claims the letter may have been a joke (link: Chemist who ordered night and weekend work replies to critics). Selected quote below:

I wonder whether you would think it fair to be judged on the basis of a letter 14 years old, especially when the comments and rash judgments are made without knowledge of the context or the circumstances surrounding the individuals involved. Indeed how does anyone out who is so quick to pass judgement and who is coming to conclusions know that it is not part of a 14-year old joke (or satire as you state) that backfired? …

Update 6: Comparatively tame letters from Paul Gassman and Albert Meyers, but they have some good information in them about standard expectations.

If you have similar letters you would like to share send them in. Any identifying information can be removed upon request.

Mitch

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The Good, The Bad, and The Ugly

Does anyone else have a difficult time trying to separate “good science” from “bad science”?  I’m a very black and white person.  I love facts and truths and logic, and that drives most of my family crazy.  Perhaps that’s why I struggle with identifying bad science; there’s seemingly no clear-cut, concise way of identifying junk that ends up published.  To be clear, I’m not talking about retractions for blatant disregard for scientific ethics.  I’d classify these situations (e.g., the Xenobe controversy, Sames’ retractions, Bell Labs, etc.) as “ugly.”  I’m particularly concerned with cases where during a presentation everyone sort of looks at each other, raises his/her eyebrows, frowns, and collectively mumbles, “Hmm.”

It seems the term “junk science” has been in use in the legal profession since the 1980’s.  Yet, despite its existence, “junk science” is actually an ambiguous concept.  In 1998, legal experts Edmond and Mercer attempted to conquer this beast by identifying “good science,” then considering outlying cases “bad.”  Here’s what they considered “the good”:

“’Good science’ is usually described as dependent upon qualities such as falsifiable hypotheses, replication, verification, peer-review and publication, general acceptance, consensus, communalism, universalism, organized skepticism, neutrality, experiment/empiricism, objectivity, dispassionate observation, naturalistic explanation, and use of the scientific method.”

Does this list really mean that everything else is considered “junk”?  I can think of a few brilliant studies that used trial and error methods in lieu of the scientific method.  Conversely, I’m aware of peer-reviewers who simply check the “publish” box without actually reading the manuscript.  As is argued on several other blogs, identifying “junk science” is a very gray area.

Perhaps one way to define junk science is to take the Jacobellis v. Ohio approach.  In a 1964 US Supreme Court case involving obscenity, Justice Stewart Potter wrote in his opinion, “I shall not today attempt to define the kinds of material I understand to be [pornography]…but I know it when I see it.”  Clearly the same frame of thought can be applied to junk science.  I am less inclined to accept the Jacobellis approach because it offers nothing tangble.

There must be some empirical qualities that set the good from the bad.  Despite all the skills I’ve learned with a mere decade of lab experience, I am disheartened to admit that I honestly never perfected the skill of detecting bad science.  So, like a responsible, up-and-coming assistant professor of chemistry, I went crawling through the literature to determine what separates the good from the bad.  Below is a list of a few things I learned.

In the spirit of Jeff Foxworthy, science might be “junk” if…

Researchers are more concerned with holding press conferences than publishing results in reputable, peer-reviewed journals. One might assume that “breakthroughs” ought to be showcased in the most prestigious journals after being subjected to a rigorous peer review process.  Fast tracking all the way to the press conference phase certainly raises some flags about credibility.  I’ve seen this phenomenon happen first-hand, and when the science is questionable, the ensuing public announcement can get really ugly (and entertaining, for that matter).

Something about the research seems off kilter. If you think something doesn’t feel right, you might be correct.  Although going with your gut will only get you so far, analysis guides such as “Tipsheet: For Reporting on Drugs, Devices and Medical Technologies” help identify specific areas for journalists to consider when examining the veracity of medical therapies.  Cook and co-workers suggested that similar checklists might likewise serve the general scientific community when evaluating the credibility of reported work.

Conflicts of interest are not explicitly disclosed. In these cases, scientific integrity might be compromised for financial, political, or other external motivations.  In developing this article, I encountered journals, funding agencies, and governing bodies that require authors to declare any potential conflicts of interest while publishing or applying for grants.  Although editors and referees try to uphold strict transparency policies, authors can still fail to report external influences and biasing.  These cases essentially touch every facet of research–cancer, testing pesticides (Berkley Scientif. J. 2009, 13, 32-34), and even drug development.  The onus is put on the audience to look into the author’s sources of funding.

The flow of logic doesn’t make any sense. Junk science may have gaping holes in experimental descriptions or proposed models.  Fortunately, overly simplistic and inaccurate scientific explanations usually evoke sharp criticism from the scientific experts.  Credible “debunkers” often attack the logic of an issue by (for example) discrediting cited authoritative opinions, identifying assumptions, and/or offering overlooked hypotheses.

Colleagues in the field are widely skeptical of the work. Mix it up with your cohorts.  A simple, “Hey, what did you think about the most recent (insert name of researcher here) article in JOC,” can shed some light on the context of published or presented findings.  “[He] hasn’t published anything reproducible in the past 20 years,” my PI once said.  “I sincerely doubt that this latest paper is anything new.”

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My Advice to First-Year Ken (Time Machine Availability Pending)

Having just successfully defended my dissertation and finding myself with spare time during a cross-country drive between Los Angeles to North Carolina, I have compiled a list of things that I did or, in retrospect, wish I had done at the beginning of graduate school. I hope that those who are just entering a program this fall will find it useful. One thing to keep in mind while reading this list is that I am primarily a synthetic chemist. Yet, I am optimistic that there is something useful to all chemists, no matter the flavor.

In no particular order:

1) Search through every nook and cranny of your lab. When you first start working you should look through every drawer/cabinet/fridge/corner in your group’s space just to get a feel for what is available to you. At some point you might need a unique item that you recall happening across during your initial search. Keep in mind that while group materials are often shared, some of the senior group members might not be happy if they find you going through “their stuff” so you might want to either ask them or do it at night when no one is around.

2) Have an extra set of clothing/shoes in desk. You never know when you will sacrifice an item of clothing on the alter of science (Ignore this point if you enjoy public nudity).

3) Use a numbering system for your files. Early in your graduate career you might be tempted to label your spectroscopic files (NMR, UV-Vis, IR, etc.) after the name of your molecules. However, unless you are going to list the full IUPAC name it will result in some acronym or abbreviation that could change over time. To avoid much frustration and ordeal while sorting through your first-year files as you write your dissertation it is much better just to name your files by notebook number or some systematic way that will not change over time.

4) Write down everything. I realize you are told this many times but you have no idea how difficult it is to recreate a procedure four years later with notes that are not up to par. If you are not motivated by the fear of your own personal frustration later on, do it for the next person that needs to recreate your results.

5) Always remain skeptical. It is very easy to convince yourself that there is a peak or signal or whatever when you want it to be there. Yet, no matter how much you want to have discovered a new phenomena or synthesized your final product, you have to double/triple check your results and use multiple measurements to be sure. If a result is to good to be true, it often is. There is nothing more devastating than to be “certain” of your results only to find out they are far from it.

6) Get a screw driver set. Although your research group may have public use tool, I strongly recommend keeping a personal set of both small and regular-sized screw drivers in your desk drawer. They will always be there and in good working condition when you need them (In consideration of point #1 – write your name on all personal items).

7) Buy Invest in a comfortable chair. Over the course of your graduate career (4-7 years) you will spend many hours in your chair, especially when writing up papers or your dissertation. Being physically sore due to a crappy chair does not help your mental well-being and thus can end up hindering your research.

8 ) Stagger your hours. No matter how close you are with your lab mates, make no mistake; you will be competing with them for lab space and equipment (rotovaps, spectroscopic machines, etc.). Although the idea of working from 6am to 4pm may not sound appealing, you can get a lot of work done when you have free reign over EVERYTHING.

9) Have a couple of 3 1/2” floppy disks in your desk. Working in a state of the art research facility does not always mean you are working with state of the art operating systems/software. In the event that you need to get data off of a machine without USB drives, running windows 98 it is handy to have your floppy disks readily available.

10) Screw up early and often and learn from it. You are going to make mistakes in lab. During your first year be prepared to fail. A lot. The key to success is to learn from your mistakes. As a senior group member I had no problem walking a first-year through a procedure or trouble shooting some issue, but if I had to do it three or four times I was less likely to help them in the future.

11) Pick and choose your battles. Although it is difficult to foresee what battles are important, especially when you are first starting your research career, the best advice I can offer is to ask yourself, “will this experiment support the narrative of my research/papers? Will it help me graduate?” For example, if you are not a synthetic chemist and only care about the properties of your final product it is not worth your time to optimize your reaction yields from 50 to 80%. If your product is valuable let someone else figure out an efficient way to make it. You should just worry about measuring pure product.

12) On your first day in lab figure out who the smartest member of your research group is and hit them with a lunch tray. Just kidding. Prison rules only apply 75% of the time in graduate school. But seriously, not every opinion from senior group members is equally valuable. Get a feel early on for who is able and willing to help you with your questions.

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Where has all the (-)-sparteine gone?

*Welcome Pipeline readers!  No really, if you have a dusty bottle of sparteine, we’ll probably take it

Our lab uses a lot of (-)-sparteine in enantioselective aldol additions, so we tend to buy large bottles which last us a while.  As such, we haven’t had to order (-)-sparteine in a while.  But our bottle is getting low (read: there are a few hundred microliters left), and it’s time to order more.

But it’s all gone.

All of it.

No one sells (-)-sparteine anymore.  Acros.  Fisher.  Alfa Aesar.  VWI.  Strem.  TCI.  I’m sure I’m missing some, since I don’t actually do the ordering.  Our ordering guy called Aldrich specifically, and was able to order three 10 mL bottles (probably the last available in the world).

Well, today we get a letter from Sigma-Aldrich telling us… they’re canceling our order.  They’re not selling it anymore either.

What is going on, here?  Anyone know why the major (-)-sparteine shortage?  Is this all of a sudden or has this been happening gradually?  Is this related to the acetonitrile pinch, or is this something different?  Anyone got any black market (-)-sparteine they want to, er, not sell to us?

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Puzzling polymorphs

Polymorphism is a common and sorta crazy issue in pharmaceutical process chemistry. Basically put, a drug molecule in the solid state can have multiple crystal forms. Different impurity profiles and different crystallization techniques (solvents, heating/cooling rates) can produce different polymorphs, which can have wildly different physical properties and bioavailabilities. A famous story of troublesome polymorphism is Abbott’s ritonavir, where in the middle of manufacturing for sale (not during the R&D phase!), a new, much less soluble polymorph started showing up in batches. Moreover, once the new polymorph showed up, it was very difficult to generate the previous polymorph. Even crazier, a team of scientists went to another plant in Italy where the process was still working as desired, and soon after the team left, the new polymorph appeared. It took a crash program to understand which conditions were generating the new crystal form to get it under control.

A recent article by Pradash et al. in Organic Process Research and Development illustrates the problems of polymorphism similarly: once the authors determined that there was another crystal form (‘Form A’) than the original (‘Form B’), they undertook a screening process (looking at varieties of solvent and crystallization techniques) to find other polymorphs. Interestingly, once they discovered a new polymorph (‘Form C’), they found that it was impossible to generate Form B in their laboratories. They selected Form C for its physical properties and moved it into the pilot plant; lo, they then found Form D. This new crystal form began predominating and “those seeded crystallization processes that consistently produced Forms A and C started to produce predominately Form D in the laboratory.” (Click on image to see pictures of the polymorphs and the structure itself.)

When I read these accounts, I am filled with admiration for pharmaceutical process chemists, the interesting science that they get to do and the vast reserves of patience and sangfroid they must have.  Chemistry (and manufacturing chemistry, especially!) is based on reproducibility and consistency; when issues arise, I suspect that there is a great deal of checking and double-checking to make sure that “this is really happening to us.” Also, I can’t help but wonder if those process chemists, when these issues are discovered, wonder if the laws of the physical universe are being temporarily suspended and some Loki-like diety is having its way with them.

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Science as Art

Princeton University’s Art of Science contest has produced a gallery of pretty spectacular images of science in action.

This is the fourth Art of Science competition hosted by Princeton University. The 2010 competition drew more than 115 submissions from 20 departments. The exhibit includes work by undergraduates, faculty, research staff, graduate students, and alumni.

The 45 works chosen for the 2010 Art of Science exhibition represent this year’s theme of “energy” which we interpret in the broadest sense. These extraordinary images are not art for art’s sake. Rather, they were produced during the course of scientific research. Entries were chosen for their aesthetic excellence as well as scientific or technical interest.

Interestingly, first second and third prize were determined according to the golden ratio, with first prize earning $250, second prize earning $154.51, and third prize earning $95.49.

Be sure to check out all the images, many of them are quite striking.  Clicking on the images gives a caption explaining what you’re looking at.

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Nature Has a Graphical Abstracts Problem

Or I should say, it had a problem. The most annoying thing about Nature journals, not including Nature Chemistry, is they do not have a graphical abstract associated with their rss feed or even in their Table of Contents. However, I made a hack to view Nature with an associated graphical abstract over at ChemFeeds.

link: Nature via ChemFeeds

I also went ahead and made it for all the other Nature journals.

• Nature
• Nature Chemistry (actually already had this one, but including it for completeness.)
• Nature Physics
• Nature Neuroscience
• Nature Nanotechnology
• Nature Cell Biology
• Nature Medicine
• Nature Methods
• Nature Biotechnology
• Nature Immunology
• Nature Materials
• Nature Chemical Biology
• Nature Genetics

If you happen to be a Nature lover you can see them all with this link: All Nature.

If some of the feeds don’t have many abstracts within them it is because they are very new and more abstracts will be added automatically as Nature updates their AOP feeds.

Update: PNAS ADDED!

Update 2: Science Added.

Mitch

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How’s your laundry’s chemical hygiene?

Credit: University of Ottawa EH&S

A recent report from the President’s Cancer Panel on the environmental causes of cancer* had a rather interesting recommendation relevant to chemists. As to what you could do to lower your risk and your family’s, here’s what it said (page 111):

“Family exposure to numerous occupational chemicals can be reduced by removing shoes before entering the home and washing work clothes separately from the other family laundry.”

So what do you think of that? As chemists, we are presumably more exposed than the typical person, although I suspect that there are industrial workers (coal miners?) who are even more exposed than us.

I know that I have typically avoided bringing my shoes into the home (but, then again, I’ve always taken off my shoes before I enter my home). Recently, I have begun washing my work clothes separately from my family’s. Due to my work circumstances, I’m guessing that I carry home more compound that the average chemist. Then again, it’s the same washing machine. Short of running an ethanol rinse between washes (can you imagine the cost?), I don’t know if there’s a good answer for that one.

I’m terribly interested to know what other people’s habits are about their clothing and chemical hygiene? Do you let your kids hug you when you walk in the door from work? Do you let your dog chew on your work shoes? Inquiring minds want to know…

*Folks (e.g. Derek Lowe) have been pretty critical of the report. I’ve noticed that it’s pretty long on assertion myself. Nonetheless, it’s an interesting topic.

Photo from the University of Ottawa’s lab EH&S site.

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