The RedPen/BlackPen Guide To The Sciencing!

I think a lot about the process of doing science. I realized that there is a popular misconception about the linearity and purposefulness of doing science. In my experience that’s not at all how it usually happens. It’s much messier and stochastic than that- many different ways of starting and often times you realize (well after the fact) that you may not have had the most clear idea of what you were doing in the first place. My comic is about that, but clearly a little skewed to the side of chaos for comic effect.

The RedPen/BlackPen Guide To The Sciencing

The RedPen/BlackPen Guide To The Sciencing

A couple of links here. First to Matthew Hankins for the “mostly partial significance”, which was inspired by his list of ridiculous (non)significance statements that authors have actually used. Second is to myself since one of the outputs of this crazy flow chart-type thing is writing a manuscript. Which might go something like this.

Update: Just had this comic pointed out to me by my post-doc. Which is funny, because I’d never seen it before. And weirdly similar. Oh man. I was scooped! (oh the irony)

Syrah Ice Cream

This is the Syrah I used- but not this vintage.

This is the Syrah I used- but not this vintage.

Given that I had some extra red wine (I know that seems like an oxymoron) that needed to be used and I was making ice cream (fresh picked strawberry- delicious) I thought, “what about making red wine ice cream?” Given the age of Google I knew I could search and find where other people had attempted it – and probably find recipes, but I actually thought it would be more fun just to go forward by myself. But I did solicit input on Twitter. I got a few great suggestions- first was using a wine reduction and second was a wine sorbet.

Since I was already geared up for ice cream I figured I’d save the sorbet attempt for next time. I first did a red wine reduction, using about ½ bottle of Syrah from Horse Heaven Hills in Washington and about ½ cup sugar. I just put it on the stove and simmered for about an hour. When it was finished I had about ¾ cup of a nice sweet syrup. Tasting this I realized that it was sweet, and rich, but did not have a strong wine flavor, which I was going for in the eventual product. I therefore decided to add more ‘fresh’ wine, but not too much since the alcohol will prevent the mix from freezing. I also decided to add a little vodka to give a bit of a punch. The resulting mixture has a nice purple color. Putting it in the ice cream maker (we have a Hamilton counter-top model where you freeze the container in advance) and having the direct comparison with the previous strawberry ice cream I could see that the red wine mixture was slower to freeze. I just let it mix longer, but it never got as solid as the regular ice cream. However, the result (after about 40 minutes of mixing) was about the

Syrah ice cream in mid-mix

Syrah ice cream in mid-mix

consistency of yogurt. I put it in the freezer overnight but it never really solidified. The ice cream turned out like soft-serve, holds its structure in the bowl, but very soft. This is certainly due to the alcohol content and I guess you could cut down on the amount of red wine or eliminate the vodka to make it stiffer. Tasting the ice cream right when it was finished wasn’t very conclusive because by that time I had already supported my creativity with several glasses of wine. The wine flavor, therefore, didn’t come through at the time. Tasting the next morning I was pleasantly surprised. As mentioned on Twitter, cream can mute flavors, and there certainly isn’t a huge up front red wine flavor.

But the ice cream is sweet, flavorful, and then has some lingering complexity reminiscent of the ‘parental’ Syrah. It would be fun to try out some different varietals (maybe a Cab for a darker flavor or a Pinot Noir for a lighter flavor? For real wine reviews please see Great Northwest Wine– who also had a direct hand in prompting this exercise). The alcohol kick comes through a bit as well- but is not overwhelming. Although I was going for more of an overt red wine flavor, I think this came out pretty darn good- and would make a very nice complement to, say a dark chocolate torte for a dessert.

Syrah Ice Cream

  • ½ recipe Ben and Jerry’s Sweet Cream Base #1
  •             1 egg
  •             3/8 c sugar
  •             1 c cream
  •             ½ c milk

Whisk egg until frothy (about 2 minutes)- then add sugar in several bits. Mix well for about 2 minutes. Whisk in cream and milk.

  • ¼ cup red wine reduction
  •             ½ bottle red wine (can be any kind but I used one with stronger flavor- as opposed to a Pinor Noir, e.g.)
  •             ½ cup sugar
  •             simmer until reduced 1/3 (about an hour)
  • ½ cup red wine
  • 1 T vodka

Mix these ingredients together then stir into cream base. Mix in ice cream maker until creamed. Transfer into container and freeze.



Have laptop, will travel

One of the great things about being a purely computational researcher is that, nowadays, my office is pretty much wherever I want it to be. I’ve got my laptop, WiFi is omnipresent, and I have noise-canceling headphones for the serious business. There are lots of reasons that I have to be at my office – meetings and increased ability to focus being primary. However, it’s not the case that you have to be purely computational to get a lot out of working in non-traditional locales. Writing is the place where we all (as researchers) can do this. Writing manuscripts and grants being the biggest time sucks. Some of you will have the ability to be flexible in your actual work time, others this might pertain mostly to the ‘extra’ work you do writing grants and papers.

So here is my random collection of thoughts on this topic.

Why take your work outside the standard work environment?

  1. Flexibility and efficient use of time. If you have your laptop with you you can fit in writing wherever you are (see list below). This allows you to use your time well instead of standing around checking Facebook on your phone. Not all writing work is  suited for the short bits of time (probably no less than about 20-30 minutes at a time) but if you plan what to work on you can get a lot done this way. If you don’t have your laptop a surprising amount of work can get done with just a pen and paper.
  2. Freedom from distraction. OK, a coffee shop can be a pretty distracting place, that’s a given. But sometimes being in your office can be pretty distracting too. People stop by to chat for a minute, phones ring, drawers need organizing, etc. If you can ignore the distractions outside your office (wherever you’re choosing to work) then this can be a productive way to go. Also, try working somewhere WITHOUT WiFi (it can be done)- and cut out the social media chatter.
  3. Creative stimulation. Changing your work environment drastically can give you a shot of creative energy. It can be refreshing wot work outside at a park, or while enjoying a glass of your favorite beverage at a cafe or bar.

What to work on?

  1. Grants
  2. Manuscripts
  3. Reviewing papers/grants
  4. Catching up on answering emails
  5. Reading papers- no laptop required
  6. Planning and outlining- also no laptop required, use a pen and notebook

Where can you do this?

  1. Coffee shop. Everyone pretty much knows about this one. Can be distracting, but find a quiet corner and bring headphones. Also, try not to drink 15 double espressos while you’re there (not that I would have ANY experience with that)
  2. The Mad Scientist enjoying a beer after a long day meeting and about to do some grant writing at a McMenamin's pub in Portland

    The Mad Scientist enjoying a beer after a long day meeting and about to do some grant writing at a McMenamin’s pub in Portland

    Bar/pub. These can be awesome places to work- probably not on a Friday or Saturday night, but other times. Many have WiFi and they have BEER! Also, try not to drink 8 beers while you’re there. Alcohol is actually a consideration since it can affect your motivation pretty severely. Ordering ONE beer and some food works OK for me, but certainly use your best judgement- and they will always have alternate non-alcoholic beverage options.

  3. Public library. This is really just a no-brainer. No cost (though many libraries have coffee shops attached and allow you to bring covered cups in), free WiFi, lots of sitting areas, quiet atmosphere, surrounded by the smell of knowledge.
  4. Park. Working outside is sometimes really nice in nice weather. If you’re lucky enough to have workable weather (not too hot, not too cold, not too windy or rainy) then find a table in the shade and settle in. I’ve never found this particularly effective myself, though the idea is wonderful, but I’m sure it could work for others.
  5. Doctor/dentist office, DMV, etc. This option is one I use quite a bit, but it only works for things that you can do a little bit on before being interrupted. I find that making todo lists and outlines work well here. Also reading background material can also work well.
  6. Car. Not while you’re driving! I mean if you’re sitting and waiting for something or someone this can be a good time too.
  7. Public transportation. When I was in Seattle I rode the commuter train in from Everett to work several times a week. A great place to work. An hour of uninterrupted time while beautiful countryside rolls by. Buses can work too, though not always for actual writing since often they bump and move too much for a laptop. Subways/metros also work well. Of course, this is pretty dependent on the density of people. It’s really hard to do anything productive when you have an elbow in your face and about 6 inches of standing room.
  8. *that's me in the seat behind Rex, by the way.

    *that’s me in the seat behind Rex, by the way.

    Airplane/airport. So much wasted time in airports- which are great places to work if you find the right spots. Airplanes can be a bit problematic in terms of an actual laptop (I find I can do it if I type like a T-rex) but I bring papers to read and a notebook to do planning and write ideas. In airports try to find places where there aren’t many people- away from your departing gate if you have time. More chance of getting a power outlet and fewer distractions. If you’re really in need of an outlet try looking in places where other people aren’t going to be sitting (hallways and walkways) and sit on the floor- it can be done.

  9. Hotel. Also in the traveling realm. Hotels can be excellent places to write. Free from a lot of the distractions and obligations of home and office. If you have extra time after a day at a conference or between sessions or before you catch your plane- use it. Many hotels are set up with desks, comfy chairs, outlets, coffee makers, and WiFi. When I travel to the east coast and my return flight is early I will frequently work through the night. Not for everyone, but I’m a night owl and I find it easier to do this (sometimes) than to sleep for a few hours then drag myself out of bed at 5 AM (3 AM my time) to get to the airport. Also, no danger of oversleeping – unless of course you accidentally crash. So if you do this make sure to arrange a wake up call and set an alarm for backup.
  10. Other locations. Be on the lookout for other opportunities. I have worked on a grant while pouring wine for a wine tasting at a friend’s house (not a wine-tasting party, mind you- this was a professional activity, so quite a bit of down time). That was pretty epic really but it still didn’t get my grant funded.



Magic Hands

Too good to be true or too good to pass up?

Too good to be true or too good to pass up?

There’s been a lot of discussion about the importance of replication in science (read an extensive and very thoughtful post about that here) and notable occurrences of non-reproducible science being published in high-impact journals. The recent retraction of the two STAP stem cell papers from Nature and accompanying debate over who should be blamed and how. The publication of a study (see also my post about this) in which research labs responsible for high-impact publications were challenged to reproduce their findings showed that many of these findings could not be replicated, in the same labs they were originally performed in. These, and similar cases and studies, indicate serious problems in the scientific process- especially, it seems, for some high-profile studies published in high-impact journals.

I was surprised, therefore, at the reaction of some older, very experienced PIs recently after a talk I gave at a university. I mentioned these problems, and briefly explained the results of the study on reproducibility to them- that, in 90% of the cases, the same lab could not reproduce the results that they had previously published. They were generally nonplussed. “Oh”, one said, “probably just a post-doc with magic hands that’s no longer in the group”. And all agreed on the difficulty of reproducing results for difficult and complicated experiments.

So my question is: do these fabled lab technicians actually exist? Are there those people who can “just get things to work”? And is this actually a good thing for science?

I have some personal experience in this area. I was quite good at futzing around with getting a protocol to work the first time. I would get great results. Once. Then I would continue to ‘innovate’ and find that I couldn’t replicate my previous work. In my early experiences I sometimes would not keep notes well enough to allow me to go back to the point where I got it to work. Which was quite disturbing and could send me into a non-productive tailspin of trying to replicate the important results. Other times I’d written things down sufficiently that I could get them to work again. And still others I found that someone else in the lab could consistently get better results out of the EXACT SAME protocol- apparently followed the same way. They had magic hands. Something about the way they did things just *worked*. There were some protocols in the lab that just seemed to need this magic touch- some people had it and some people didn’t. But does that mean that the results these protocols produced were wrong?

What kinds of procedures seem to require “magic hands”? One example is from when I was doing electron microscopy (EM) as a graduate student. We were working constantly at improving our protocols for making two-dimensional protein crystals for EM. This was delicate work, which involved mixing protein with a buffer in a small droplet, layering on a special lipid, incubating for some amount of time to let the crystals form, then lifting the fragile lipid monolayer (hopefully with protein crystals) off onto an EM grid and finally staining with an electron dense stain or flash freezing in liquid nitrogen. The buffers would change, the protein preparations would change, the incubation conditions would change, and how the EM grids were applied to our incubation droplets to lift off the delicate 2D crystals was subject to variation. Any one of these things could scuttle getting good crystals and would therefore produce a non-replication situation. There were several of us in the lab that did this and were successful in getting it to work- but it didn’t always work and it took some time to develop the right ‘touch’ to get it to work. The number of factors that *potentially* contributed to success or failure was daunting and a bit disturbing- and sometimes didn’t seem to be amenable to communication in a written protocol. The line between superstition and required steps was very thin.

But this is true of many protocols that I worked with throughout my lab career* – they were often complicated, multi-step procedures that could be affected by many variables- from the ambient temperature and humidity to who prepared the growth media and when. Not that all of these variables DID affect the outcomes but when an experiment failed there were a long list of possible causes. And the secret with this long list? It probably didn’t include all the factors that did affect the outcome. There were likely hidden factors that could be causing problems. So is someone with magic hands lucky, gifted, or simply persistent? I know of a few examples where all three qualities were likely present- with the last one being, in a way, most important. Yes, my collaborator’s post-doc was able to do amazing things and get amazing results. But (and I know this was the case) she worked really long and hard to get them. She probably repeated experiments many, many times ins some cases before she got it to work. And then she repeated the exact combination to repeat the experiments again. And again. And sometimes even that wasn’t enough (oops, the buffer ran out and had to be remade, but the lot number on the bottle was different, and weren’t they working on the DI water supply last week? Now my experiment doesn’t work anymore.)

So perhaps it’s not so surprising that many of these key findings from these papers couldn’t be repeated, even in the same labs. There was not the same incentive to get it to work for one thing- so that post-doc or another graduate student who’s taken over the same duties, probably tried once to repeat the experiment. Maybe twice. Didn’t work. Huh? That’s unfortunate. And that’s about as much time as we’re going to put in to this little exercise. The protocols could be difficult, complicated, and have many known and unknown variables affecting their outcomes.

But does it mean that all these results are incorrect? Does it mean that the underlying mechanisms or biology that was discovered was just plain wrong? No. Not necessarily. Most, if not all, of these high-profile publications that failed to repeat spawned many follow-on experiments and studies. It’s likely that many of the findings were borne out by orthogonal experiments, that is, experiments that test implications of these findings, and by extension the results of the original finding itself. Because of the nature of this study it was conducted anonymously- so we don’t really know, but it’s probably true. This was an important point, and one that was brought up by these experienced PIs I was talking with, is that sometimes direct replication may not be the most important thing. Important, yes. But perhaps not deal-killing if it doesn’t work. The results still might stand IF, and only if, second, third, and fourth orthogonal experiments can be performed that tell the same story.

Does this mean that you actually can make stem cells by treating regular cultured cells with an acid bath? Well, probably not. For some of these surprising, high-profile findings the ‘replication’ that is discussed is other labs trying to see if the finding is correct. So they try the protocols that have been reported, but it’s likely that they also try other orthogonal experiments that would, if positive, support the original claim.

"OMG! This would be so amazing if it's true- so, it MUST be true!"

“OMG! This would be so amazing if it’s true- so, it MUST be true!”

So this gets back to my earlier discussions on the scientific method and the importance of being your own worst skeptic (see here and here). For every positive result the first reaction should be “this is wrong”, followed by, “but- if it WERE right then X, Y, and Z would have to be true. And we can test X, Y, and Z by…”. The burden of scientific ‘truth’** is in replication, but in replication of the finding– NOT NECESSARILY in replication of the identical experiments.

*I was a labbie for quite a few of my formative years. That is, I actually got my hands dirty and did real, honest-to-god experiments, with Eppendorf tubes, vortexers, water baths, cell culture, the whole bit. Then I converted and became what I am today – a creature purely of silicon and code. Which suits me quite well. This is all just to add to my post a “I kinda know what I’m talking about here- at least somewhat”.

** where I using a very scientific meaning of truth here, which is actually something like “a finding that has extensive support through multiple lines of complementary evidence”

Unicorn lovers and pinksters unite!

Last year GoldieBlox released a few ads that I thought were great. You’re probably familiar with them (see below) but they are advertising a building kit targeted especially at girls. These kinds of products are great and much needed. The idea is to counter the years and years of placing girls in pink marketing boxes with a limited number of career-directed options (NO pink CEOs, pink scientists, pink explorers, pink astronauts). Girls WILL like pink and sparkly things. They WILL like princesses, unicorns, and small sad-eyed puppy dogslego-woman-scientist. As many will know this remains a problem- there’s lots of marketing that is still directed that way. However, there has been a recent surge in non-traditional products directed at girls: LEGO women scientists figures, building kits for girls, These are simply great options and great advances and by all means they should continue to be developed, expanded, and marketed.

But back to the ad and my main point. When we push for something, we seem to have to push against something else- we draw lines to discriminate “us” from “them”. For girl power we should be pushing back against the oppressive, ingrained, male-dominated power structure that has been in place in our society for years. However, too often it seems that we push against the wrong things: those girls who love pink, who like unicorns, who wish they were princesses. You can argue about whether this is a good thing or not, but the fact is that these are girls too. This anti-pink message is too often conveyed in marketing and people’s general reactive attitudes against the traditional, including mine- in the context of saying something good: We should empower girls to achieve and not be held back– along with something not so good: not like those other girls who won’t achieve. What this kind of reactive attitude is saying is this:

Because you like pink you can not be an engineer. You can not be a scientist. You can not be an astronaut. Girls who like unicorns do not do that. They are less than girls that don’t like these things.

Make no mistake- I like these ads, I think they’re funny and they make me laugh. But that doesn’t change that they do so at the expense of a group of people who have nothing but potential to be squashed. These GoldieBlox ads aren’t terrible in this way- the ‘pink unicorns’ are things (toys and some cartoon on the TV), not a set of girls, but it remains that the implication is that liking pink is bad and won’t take you anywhere. Clearly liking a particular color shouldn’t have an ounce of an effect on what you will do later in life- or even what you can do now. This was pointed out to me after I posted the ad to my Facebook page, by a good friend who has girls who do like princesses. And it is an excellent point.

So, in a way, this is a limited example. But it highlights a much larger problem with human nature. Humans LOVE to draw lines. Them and us, us versus them. When lines are drawn around another group of people based on some set of attributes (favorite color, gender, skin color, type of pants worn) then all those inside the group suddenly acquire- in your perception- a set of other attributes from that group, whether or not these are accurate and whether or not the individual you’re talking about has said attributes. We *know* things about “those sorts of people”. This is one of the very natural tendencies that we all have, we all indulge in, and we all must do our best to fight against.

Here’s the GoldieBlox ad:

Here is another ad that I think is particularly well done. It highlights how perceptions and language are important- but also demonstrates a point about the tendency of humans to group:

If you have kids try this on them. Ask them to throw ‘like a girl’ and see what they do.