Bill Hicks’ 12 Principles of Comedy — for Scientists

Mark Frauenfelder over at BoingBoing recently shared this advice from wonderful comedian Bill Hicks, and noted that it likely applied to far more than comedy:

12 Principles of Comedy

  1. If you can be yourself on stage nobody else can be you and you have the law of supply and demand covered.
  2. The act is something you fall back on if you can’t think of anything else to say.
  3. Only do what you think is funny, never just what you think they will like, even though it’s not that funny to you.
  4. Never ask them is this funny – you tell them this is funny.
  5. You are not married to any of this shit – if something happens, taking you off on a tangent, NEVER go back and finish a bit, just move on.
  6. NEVER ask the audience “How You Doing?” People who do that can’t think of an opening line. They came to see you to tell them how they’re doing, asking that stupid question up front just digs a hole. This is The Most Common Mistake made by performers. I want to leave as soon as they say that.
  7. Write what entertains you. If you can’t be funny be interesting. You haven’t lost the crowd. Have something to say and then do it in a funny way.
  8. I close my eyes and walk out there and that’s where I start, Honest.
  9. Listen to what you are saying, ask yourself, “Why am I saying it and is it Necessary?” (This will filter all your material and cut the unnecessary words, economy of words)
  10. Play to the top of the intelligence of the room. There aren’t any bad crowds, just wrong choices.
  11. Remember this is the hardest thing there is to do. If you can do this you can do anything.
  12. I love my cracker roots. Get to know your family, be friends with them.

So here goes:
12 Principles of Comedy Science

[1] There is surely something to be said for being yourself, but beyond that, find a way to be in high demand. Maybe you’re a master of optogenetics or some other technique, perhaps you’re the lab guru when it comes to statistics, the literature or maybe you bring much needed positivity and perspective to the lab. Regardless of how you do it, find a way to be valuable to those around you.

[2] You need to be innovative. You need to find creative solutions to problems, or even better, find new and interesting problems. Avoid the predictable research.

[3] Be ruthless in your focus. Only research problems you find interesting, and minimize tasks that take you away from that research.

[4] Don’t wait for others to stumble across the significance of your research, present your research in a way that the significance is self-evident.

[5] You don’t have to look very far to find horror stories of projects gone awry with dramatic and terrible consequence. Don’t lock yourself to a sinking ship.

[6] Say use, not utilize. Avoid unnecessary jargon. Correlation != causation. Triple check for typos. Avoid the simple and common errors of others.

[7] Don’t spend years of your life doing something that makes you miserable. Maybe you love teaching more than research, or perhaps industry is a better fit than academia. Being a scientist means different things to different people, and there is little to be gained from success if you don’t find your work fulfilling.

[8] Always return to the fundamentals. What is my hypothesis? How am I testing it? Why does this problem matter?

[9] Less is more. Design elegant experiments which speak for themselves. Write simply and clearly. Speak directly and without embellishment.

[10] Always know your audience.

[11] Remember this is one of the hardest things there are to do. If you can do this you can do anything. Be proud of your accomplishments and contributions.

[12] Connect with those around you. Your family, your friends, other members of your lab, others in your field. Never forget where you have come from, or where you dream to go. Find the people who will help you get there.

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BioPrinter Part 3

This is the third in a series of posts about a BioPrinter project I’ve been working on. To read the previous two posts about my experiences before and after the Boston Science Hack Day 2015 see: https://scienceroastery.wordpress.com/2015/01/26/the-bioprinter-at-boston-science-hack-day-2015-part-2/ and https://scienceroastery.wordpress.com/2015/01/06/the-bioprinter-at-boston-science-hack-day-2015/

Last week I had the opportunity to test out out the BioPrinter with some live cells! I was impressed at how easily the whole process went. I unpacked the printer–it survived the trip back from Boston surprisingly well–and tested it with a few practice images. Surprisingly, the most difficult part of this step was disassembling the ink head and removing the ink. The plastic is pretty hard and doesn’t like to be opened with a box cutter. However, once the ink was rinsed out with some distilled water, I was able to put in ~2mL of cell culture and print them onto a plate without difficulty!

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I was happy that the grids of cells from the first run came out as a series of discrete dots albeit in lines that are slightly askew. The uneveness of the lines is mostly due to the momentum generated by the movement of inkhead and petri dish during the print process. Down the road we’re interested in using this printer to dispense cells into 384 well plates for culturing experiments, and the fact that the printer produced individual spots suggests that we will be able to use the printer to “load” those plates.

This version of the printer is mostly a proof-of-concept. As you can see, there is some splatter on the plates due to the height of the inkjet. We’re limited in this respect because of the holes I originally drilled into the frame holding up the top motor/inkhead assembly. The lowercase letters are also a little difficult to read, so we might stick to capitals for a while. I’ll also want to eventually increase the print area. The CD drive heads limits us to about a 100×100 pixel print area which is a little less than 1.5 x 1.5 in. Replacing these with motors similar to those used in various RepRap projects would give us a substantially larger print area.

My next attempt will be to print a gradient of cells and/or nutrients on the plate. The nutrient gradient might pose a bit of a problem because any nutrient solution we dispense on the plate is likely to diffuse through the agar, but we won’t know to what extent this will be an issue unless we try!

If you are interested in the code used to run the printer, please take a look at these two GitHub repos and email me if you have any questions. I would be happy to walk anyone through the code:

https://github.com/tpudlik/bioprinter_host and https://github.com/tpudlik/bioprinter_arduino/tree/motor

Before you go, here’s a video of the printer in action!

The BioPrinter at Boston Science Hack Day 2015 (Part 2)

I spent this past weekend in Boston at the Science Hack Day hosted by MIT’s Media Lab. Being in the Media Lab was an incredible experience and probably deserves its own post, but suffice it to say that those who are lucky enough to study there must have the time of their lives.

As detailed in an earlier post, I have worked on-and-off since 2013 on a BioPrinter using blueprints from the Silicon Valley-based biohacker space, Biocurious. The start of this project in 2013 marked my first foray into the world of code and electronics. Having spent countless hours streaking plates to cultivate soil bacteria, I was thrilled at the prospect of writing programs to drive a machine to print cells. Unfortunately this project was moved to the backburner as I started to realize how difficult it can be to writer drivers using C++.

I was excited to attend Boston Science Hack Day, and I found that it was a great opportunity to meet up with some incredibly talented individuals and finally write the software to drive the BioPrinter.

OLYMPUS DIGITAL CAMERA

(Left to Right) Evan Pipho, Daniel Burkhardt, Ed Klacza, Ted Pudlik, Pascal Timshel, and Ari Roshko

It was amazing to see how the group was able to self-organize so easily. There was no “group leader” or director to the project. I outlined the goals I had for this printer and everyone in the group picked a task to which they felt most suited. Ted and Pascal wrote a program in Python to convert bitmap PNG files into CSVs and then a second program to convert CSVs to G-code (a language designed in the 50s to drive computer numerical controlled (CNC) machinery). Evan wrote a great interpreter that takes G-code commands and translates these orders into electrical pulses delivered to the stepper motors. Ed and Ari and Evan and Ted helped me to troubleshoot hardware issues. By the end of the weekend we produced a proof-of-concept that printed “I ❤ BSHD” on a post-it note which was incredibly satisfying.

OLYMPUS DIGITAL CAMERA

I think it’s interesting to consider the factors that made this BSHD a success. I think much is owed to our amazing organizers: Jessica Polka, Edward Kim, and Willow Brugh. They organized a space that was conducive to getting work done. We weren’t for want of food or water or fun things to look at around us. The time limits of a hackathon seem to play a big role in our group’s ability to focus on a single problem for ~20 hours over the course of two days. I also shouldn’t be quick to forget that we couldn’t have finished this project without the skills and knowledge each member brought to the table.

Up next: printing cells!

Probing Microbial Dark Matter and Discovering a Novel Antibiotic

Last week Kim Lewis’s lab at Northeastern University published a paper in Nature describing a novel antibiotic they call teixobactin, marking the first discovery of a natural antibiotic in decades1. Although many news articles focus on the medical and pharmaceutical impacts of this discovery, my lab has been talking about it for a different reason. This discovery shows the usefulness of cultivating soil bacteria and underlines the benefits of the isolation chip (iChip) for doing so. Quite a few undergraduate and graduate students in my lab have worked on cultivating soil bacteria, and we’re always looking for new techniques.

A diagram of the iChip. (A,B) First a chip is inoculated with a dilute inoculum such that there is only one bacterium per well. (C) Then two semipermeable membranes are attached to either side of the chip which is then incubated in soil. (Ling et al. 2015.)

One of my first projects in the DeAngelis lab was to cultivate soil bacteria from the Harvard Forest in order to characterize the diversity of bacteria that drive soil biogeochemical (I hate this term but I can’t seem to find a less jargon-y descriptor) cycles. The idea is relatively simple. Find some dirt, smear it on a plate, and see what grows. I thought, How hard could it be? As it turns out: Very.

The issue is that only about 1% of bacteria can survive in standard laboratory conditions (we know that we’re missing 99% based on microscopy and cultivation-independent sequencing). This missing 99% has many names depending on who’s talking about it. They’re the unculturables, or the uncultivated, or the Great Plate Count Anomaly, or my personal favorite: microbial dark matter. At the end of the day, we do not know what these 99% of bacteria bacteria need in order to grow on a plate. Until we can grow them on a plate, how can we study when they need to grow? You can see how this becomes a difficult problem to solve.

One side of this problem is fairly simple: some bacteria grow very slowly, and it can be difficult to wait for months until these small colonies appear. Instead it is much easier to culture the large and clearly visible colonies that grow after only a couple of weeks and often crowd out slow-growers. Finding the slow growers requires the patience to remove colonies which form more quickly followed by months of waiting for slowly growing colonies to pop up. After having a few conversations with colleagues about this, I have a hunch that reluctance to make such an effort plays a small role in the number of uncultured bacteria.

Impatience aside, the lack of knowledge of the necessary biotic and abiotic growth factors in the soil is a much more complicated problem to solve. We lack information about what these bacteria need to grow. It’s difficult to know what to manipulate: pH, temperature, concentration of particular compounds, even solidifying agents like gellan gum, agar, agarose, etc. Exhaustively testing all of these conditions would require massive efforts, and might miss some unknown factors of which we are unaware. Additionally complicating things, some bacteria prefer to grow in close association with other bacteria. For example, Acidobacteria are often found in a biofilm with other bacteria and it can be difficult to separate them from their peers.

There are a variety of techniques scientists have used to tackle these problems. These range from the fairly straightforward–dilute media, long incubation times, and cultivation in microoxic atmospheric conditions–to the high-tech (think optical tweezers and laser microdissection). You can find all of these reviewed in a 2012 article by Vam Pham and Jaisoo Kim of Kyonggi University2.

The iChip is an elegant strategy to cultivate uncultivable bacteria that addresses both the effort required to cultivate slow-growers and the lack of knowledge about the optimal growth conditions for bacteria we haven’t characterized. The chip is made from hydrophobic plastic and has around 400 1.25µL wells. To inoculate a well, cells are extracted from soil and diluted so that there is approximately 1 cell per 1.25µL of inoculum. The cell is then dipped in inoculum, the wells are filled, and then two semipermeable membranes are fixed in place on the top and bottom. This solves the issue of needing to pick out quickly growing bacteria while waiting for slow growers because there should only be  ~1 microbe per well. The inoculated iChip is then placed in a slurry of soil for 10 weeks. After this time, individual wells are popped out of the iChip and used to inoculate plates. By growing these bacteria in single wells in their native soil environment until they form colonies, it is possible to increase the rate of cultivability from 1% to 50%3!

Dr. Lewis’s lab used this technique to screen 10,000 isolated bacteria for antibiotic production, but this technique should be widely applicable to many pursuits. Studying previously uncultured bacteria has offered insight into new enzymes for biofuel production, revealed new phyla of bacteria, and helped us to better understand the world beneath our feet. I know a few of us in the lab have toyed with the idea of implementing these techniques for our own projects at the Harvard Forest.


References:

  1. Ling, L. L. et al. A new antibiotic kills pathogens without detectable resistance. Nature advance online publication, (2015).
  2. Pham, V. H. T. & Kim, J. Cultivation of unculturable soil bacteria. Trends in Biotechnology 30, 475–484 (2012).
  3. Nichols, D. et al. Use of ichip for high-throughput in situ cultivation of ‘uncultivable’ microbial species. Appl. Environ. Microbiol. 76, 2445–2450 (2010).

The Ph.D. Grind by Philip Guo

“Here is an imperfect analogy: Why would anyone spend years training to excel in a sport such as the Ironman Triathlon—a grueling race consisting of a 2.4-mile swim, 112-mile bike ride, and a 26.2-mile run—when they aren’t going to become professional athletes? In short, this experience pushes people far beyond their physical limits and enables them to emerge stronger as a result. In some ways, doing a Ph.D. is the intellectual equivalent of intense athletic training.”

The Ph.D. Grind is a freely available e-book written in 2012 by Professor Philip Guo (currently at the University of Rochester) shortly after the completion of his Ph.D. in Computer Science at Standford University. The book is intended for a diverse audience, and is entertaining to read (I opened it on my smartphone and read it over the holidays). The book attracted my interest because it was written immediately following Professor Guo’s time at Stanford allowing for as unbiased of an account as possible.

I particularly identified with Guo’s depiction of the seemingly never ending and monotonous grunt work that makes up much of the day-to-day activity of a researcher. This is a struggle that anyone involved with scientific research is likely to identify and sympathize with. Here at The Science Roastery we aspire to graduate studies and subsequent research careers. As a result we frequently think and talk about how to research effectively, as well as the challenges faced in research. Guo clearly presents many of these challenges, his thoughts, and perhaps most importantly, his solutions.

This onslaught of seemingly meaningless “grunt work” needs to be carefully balanced with the big picture. In his book we observe Guo struggle with this issue, often dramatically swaying from one extreme to another. But by the second half of his time at Stanford, and certainly by the time he graduates, Guo seems to have conquered this challenge. This new found skill seems to be closely linked to his academic success. I can’t speak from experience, but it seems that the onslaught of frustrating and seemingly meaningless tasks only increases throughout one’s academic career (certainly, many faculty would make that argument). Therefore, anyone hoping to become a successful academic would be well served by considering how to best balance the big picture with countless insignificant tasks.

This daily balancing act is far from the only idea explored by Guo. Another major theme is the importance of interpersonal skills and developing meaningful relationships in order to be successful as a scientist. Similarly to Guo’s journey with the “balancing act”, his interpersonal skills develop at a similar rate. Guo gives particular emphasis to the idea of aligning one’s own interests with those of another party. For example, Guo shares the difficulty that he had publishing with a tenured and well established professor then compares that experience with the experience of working with a young and recently appointed assistant professor. In order to graduate Guo needs to have met specific publishing related requirements. Guo experienced success when he aligned his interest in publishing with someone who shared the same drive.

Beyond these big ideas, The Ph.D. Grind also offers a fascinating look into the life of a computer science Ph.D. student. Throughout my undergraduate years and in my current work I have had the opportunity to interact with many life science Ph.D. students, and found Guo’s experience to be interesting in it’s similarities as well as it’s differences. For someone (such as a spouse or parent) Guo’s story would seem to help one understand the enormity of Ph.D. studies — regardless of discipline.

The Ph.D. Grind does not offer much by way of flowery language, or interpersonal drama, choosing instead to focus solely on the research element of Ph.D. studies. Clearly many people have found something of value in the book: the book has been downloaded from Guo’s website more than 300,000 times, and he mentions receiving hundreds of emails in thanks.

The Ph.D. Grind is a quick and entertaining read, and is almost guaranteed to provide useful insight regarding the experience of a Ph.D. student.

Find it here: The Ph.D. Grind

A Life Decoded by J. Craig Venter

This winter, my dad gave me a copy of J. Craig Venter’s autobiography, <em>A Life Decoded. In it Venter provides a vivid account of his life. He begins by telling the reader of his childhood bicycle races against airplanes down the runway of the San Francisco Airport which foreshadows his eventual competition to publish a complete version of the human genome faster than the publicly-funded Human Genome Project. The book provides a colorful tale of the life of a scientist–major events in Venter’s life are often bookended by thrilling sailing adventures–and also describes the science behind his projects in a way that is both approachable and detailed enough for a scientific audience. Interspersed throughout each chapter are text boxes with information about Venter’s genome and specific mutations or oddities he’s found exploring it. The autobiography shows Venter to be a powerful combination: a scientist with a vision along with the scientific and political acumen to bring it to reality.

 

I came to this book at a fitting time in my career. Having applied to graduate schools, I started to think about where my life in science would take me. I expected to be questioned during interviews about my motivation to pursue graduate research and where I wanted this education. Venter’s book provided me with some perspective and inspiration. Although Venter is certainly biased in the telling of his life, some clear themes emerge. Although Venter benefited from certain privileges, it was hard work and dedication to scientific rigor that brought him success throughout his career. Venter often reiterates his PhD advisor’s advice: the best way to win a scientific argument is with data. His story also offers some hope to those who still cling to the idea that science can be a creative pursuit.  As a young scientist, I found the beginning of Venter’s career particularly meaningful, so I will share some of it here.

Life Decoded, A MECH.indd

“ [The] media has called Venter many things: maverick, publicity hound, risk-taker, brash, controversial, genius, manic, rebellious, visionary, audacious, arrogant, feisty, determined, provocative. His autobiography shows that they are all justified.”

Nature

Craig Venter was not a typical student. He describes himself in high school as a “superunderachiever,” receiving a suspension for organizing student protests and graduating by the graces of a teacher who changed an F to a D-. He was more interested in swimming than learning, and when he graduated, it seemed that he would attend Arizona State on a scholarship. Had the U.S. not invaded Vietnam, Venter might not be one of the world’s top scientists. But the U.S. did, a draft letter arrived in the mail, and the course of Venter’s life changed.

Venter served as a Navy medic in the Da Nang Navy Hospital in Vietnam from 1967 to 1968 where he saw the thin line between death and life. Many scientists, myself included, have had an experience where they realized that what drives them more than anything else is the pursuit of knowledge and understanding that’s only achievable through scientific inquiry. For me, it was a week staring through a microscope at microorganisms collected from the UMass campus pond. For Craig Venter, it seems this moment came as he treated injured soldiers, some of whom would tragically die and other miraculously survive. He tells of two patients whose outcomes appeared to be separated only by their will (or lack thereof) to live. This experience fueled his interest in understanding the mechanisms of life. In the fall of 1969, Venter began as a freshman at U.C. San Diego with a wife, a boat, and the confidence of a 23-year-old.

I often wonder how tragedy plays into the forming of a person. Venter did not have an easy life before he came to college. He had to fight for his life, learned to distrust authority, and fell in and out of love before enrolling as an undergraduate. How many of my fellow students (myself included) have experienced anything as difficult as serving in Vietnam? I understand that not everyone who goes through such painful experiences comes out better because of it, but one cannot imagine that without his time in Vietnam, the adult Venter would have the audacity and courage that propelled him throughout his career. Venter regularly cites his will to live and familiarity with competition as drivers in his life. In Vietnam, Venter learned that he needed to take charge of his life, and this certainly contributed to his successes at UCSD.

 

Venter also had the advantage of finding a mentor in Nathan O. Kaplan, an established member of the scientific community who would guide young Venter through his first experiences in the laboratory. Kaplan led a lab of more than 40 scientists, yet he took special interest in Venter’s growth. When Venter showed an interest in understanding the mechanism of action of adrenaline, Kaplan connected him with a senior researcher in his lab who was attaching adrenaline to glass beads, allowing Venter to demonstrate that the hormone acted via cell surface receptors, not some internal mechanism.

 

His relationship with Nate Kaplan seemed to jump-start Venter’s career in science. After graduating with better grades than he did in high school, Venter started working on his PhD in Kaplan’s lab. Having submitted 12 papers in three years, half in the prestigious journal Proceedings of the National Academy of Sciences (Kaplan was a member of the Academy), Venter began his 365 page thesis, defended it in front of packed auditorium, and was declared successful by a committee that included 3 department chairs. Venter then accepted an Assistant Professorship at SUNY Buffalo without the traditional post as postdoctoral researcher.

 

As a young scientist, this period in Venter’s life is the most interesting. My friends in graduate school are nowhere close to such prolificity, yet certainly most would say that they would aspire to it. The transition from delinquent high school student to wildly successful doctoral scientists is difficult to comprehend. It is unascribable solely to his experiences in Vietnam, yet it would be impossible to exclude these from his story. Certainly one cannot overlook the assistance of his advisor. It seems likely that Venter exaggerates his independence as an undergraduate laboratory–he claims to have spent only a few days consulting the scientific literature before having a firm understanding of international disputes in biochemistry. Yet there is truly something remarkable about Venter. At this point it seems that I can only point to his intellect or auspicious circumstances to explain theses successes as a young scientist. Unfortunately these two traits are difficult to cultivate in one’s self.

 

It is disappointing to be left without straightforward advice for following in the footsteps of the author when reading the autobiography of a scientific giant like Venter. I’m left thinking of the saying from Louis Pasteur, the father of microbiology, “Luck favors only the prepared mind.” I guess it’s time to start preparing.

 

The rest of Venter’s career is a tale of fighting politics and ego, of big money and large government projects. I would encourage those interested to read his autobiography: A Life Decoded. Penguin Books. 2008.

That’s a lot of coffee

From: Mark Zastrow. (2014). Science in 2015. Nature.

From: Mark Zastrow. (2014). Science in 2015. Nature.

A couple of weeks ago, Mark Zastrow at Nature published a News Feature making quantitative predictions about 2015. My personal favorites are the 1 billion cups of coffee consumed and the 260,000 new PhDs worldwide.

The coffee estimate is likely low; Zastrow divided the amount of coffee the USDA estimates the world will consume from June 2014 – June 2015 by the proportion of scientists in the world. From what I’ve seen, scientists probably consume a disproportionate amount of coffee. Zastrow cites a Dunkin Donuts survey that puts Scientist/Lab Technician at the top of coffee consumers. All those late nights in the lab need fuel!