Monthly Archives: September 2009

Why does infotech have more celebrities than biotech?

Steve Jobs, Bill Gates, Larry Page, Meg Whitman, Marissa Mayer, Guy Kawasaki, Jimmy Wales, Steve Balmer, Sergey Brin, Marc Andreessen, etc. What do these people have in common? If you said “None of them work in biotechnology,” you think like me.

The information technology industry undeniably creates more celebrities than other technological fields, like biotechnology. Biotechnology is a good comparator, because it shares with IT similar global market sizes and an ethos of entrepreneurship and innovation. So why does IT have more celebrities than biotech? Some initial thoughts.

1. More showboaters. Maybe IT types are just more attracted to flattering PR. This explains (in part) the prominence of maybe two or three people on my list, but certainly not everyone.
2. Consumers interact directly with a lot of internet businesses but less so with biotech products. Everyone uses the web, so they can better appreciate the accomplishments of Larry Page than of Herbert Boyer or Walter Gilbert.
3. Relatedly, the internet can turn average joes into hyper-successes much faster than biotechnology, because the internet does not (yet) have an FDA. Web sites and software do not need to go through clinical trials (and rightfully so), and so they can become successful much more quickly, while people are still interested in hearing about them and while the founders are young enough for teens through thirtysomethings to identify with.
4. Internet folks go to more conferences than biotech folks, possibly because working in front of a computer screen all day long is boring, so they need more celebrities to make speeches.
5. What have I missed?

What I learned in grad school, part n

So getting a Ph.D. in chemical engineering takes a long time and costs a lot of money. What else did I learn in six years? Here’s a short list:

1. My own limitations. I know I need supportive players working with me to keep me going. And I don’t just mean cheerleaders who drone on about what a great job I’m doing. A give-and-take attitude to doing science is healthy. I often have impulses to jump on to the next grandiose idea, even before I have fully worked through all the ones already on my plate. I’ve met other people who I feel dwell too much on the details, inching their project forward uninteresting bit by uninteresting bit. Real value, and real progress, comes from finding the middle ground.

2. The process, and not so much the project, is important. I now realize, after the long slough through grad school, that excelling at research does not depend on picking the best project. It’s about sustaining and pouring out your creative energies into the project, it’s about dreaming up experiments rather than dreaming up results, it’s about evaluating the data you already have without prejudice and following it where it leads. A lot of grad students lose interest in their project at some point during their doctorate. I did too, and in retrospect, it was in part due to a misplaced belief that researching an inherently great project that leads to success.

3. The magic of MIT. This place is awesome. When I see freshmen quizzing each other on the details of the biochemical pathways they have to memorize for 5.07 as they walk to lunch, I smile. When I look at MIT’s events calendar, sometimes I fantasize about taking a week of vacation to just attend lecture, talks, symposia, conferences, and discussions. I could have a beer and talk energy with folks in the MIT Energy Club and then drift over to Sloan and hear a talk about sugarcane agriculture in Brazil. While I’m at it, why not stop by one of the many venues at which undergrads show off their wacky creations, inventions, and ideas? There’s just so much. Maybe all big-name universities are like this. I don’t have much to compare my MIT experience to, but it’s been an absolutely marvelous experience.

4. Expectations about reality often disappoint. Research is the most fun when you don’t have strong expectations about the result of your experiment. The disappoint of having an idea proven wrong can seem worse than the excitement of being proven right. A related lesson for impatient people like me is that it also works best when most of your laboratory manipulations are experiments. For example, complicated assembly of synthetic gene constructs can take a long time and could easily bore me, if I were doing was following protocols. For me, making an experiment of each step was a great way to keep things interesting. What’s the best concentration of DNA to use for a ligation in step 7 of my one-month-long cloning procedure? OK, maybe it wasn’t the most groundbreaking science, but at least it was a scientific question. And keeping scientific questions in my mind helped stave off thoughts that I was just a brainless “fluid transfer specialist” pipetting fluids from one eppendorf tube to another.

5. Time is a scarce resource. Professors are very good at managing their time. If they can’t bring their full attention to a long, individual meeting with me, they don’t. Most of the faculty I interacted with had no reservations about telling me they didn’t have time to meet with me this week (or month). But, this is the key point. It’s almost always better to bug someone and have them shoo you away than to never have approached them at all. Visibility is good, and asking for someone’s time keeps you on their radar screen, even if they don’t give you any. Maybe this is true in big labs run by overstretched, always-traveling, hands-off PIs, and not in others, but the tales of many friends and colleagues, in addition to my own experience, vindicates this truism.

6. The sign of the progress derivative is more important than the magnitude. The most important thing in research is progress. In part, this is because your PI, your thesis committee, your grant manager, and your collaborators all expect you to make progress. But mainly, constant progress is a must for mental health and motivation. It goes without saying that great progress is better than no progress, but letting the perfect get in the way of the good is a mistake I think many graduate students make, especially when starting out. I know I did.

7. I learned a lot about chemical engineering and biotechnology, too, of course, but if you want to know what all those lessons were, you will have to get a Ph.D. in these topics yourself.

What happened to 3′ tags?

Colleagues of mine have begun making extensive use of 454 sequencing.
This is one of the largest (only?) commercial services for pyrosequencing-based sequence analysis of DNA. Pyrosequencing is one particular type of “sequencing by synthesis”, a cheaper, faster, and more parallelizable method for DNA sequencing than the traditional Sanger technique.

The technique works by exposing a growing DNA strand to deoxyribonucleotide triphosphates one-at-a-time. If the next base of the template is T, the next base of the newly synthesized strand should be an A. When dATP is exposed to the strand, it is incorporated into the new strand, which grows longer by at least one base pair. In the process, pyrophosphate is released, and other enzymes in the reaction mix convert the pyrophosphate into light. This is the signal detected in 454 sequencing. In contrast, when the strand is exposed to dCTP, dGTP, or dTTP, no incorporation is possible, and no light signal is generated.

One problem with sequencing by synthesis is homopolymers. Suppose the template has a stretch of Ts: TTTTTTTTAG, for example. When the reaction mix is exposed to dATP, incorporation and strand synthesis can happen all the way until the next non-T base. This generates a stronger light signal than incorporation of just one base. For short stretches of homopolymer, the strength of the light signal can be used to estimate how many bases were incorporated. But after a point, the noise overwhelms the signal, and it can be very difficult to tell CGTTTTTTTTAG from CGTTTTTTTTTAG, for example.

Last night, I was reading few papers in the history of developing pyrosequencing technology. What puzzled me is that right from the beginning, the early exponents of sequencing-by-synthesis seemed to have anticipated this problem and developed solutions. The most common approach was to put a cleavable tag on the 3′ position of the dNTP. Since polymerases require a 3′ hydroxyl group, and extra non-hydroxyl shizzle hanging off the 3′ end of a dNTP would mean that after incorporation of a single base, no new bases could be incorporated until the extra shizzle was removed. 3′ tags cleavable by light, reducing agents, or palladium, among others, were developed by various teams.

What happened to this technology? I don’t know why it isn’t used in 454 sequencing. Several possibilities:

1. Licensing issues. Are cleavable 3′-tagged dNTPs covered by intellectual property not available to 454 or Roche?

2. Problems with cleavage. As described in various publications, cleavable tags seemed to work well in the laboratory, but I wonder about the accessibility of cleavage reagents to the picotiter plates and emulsion bubbles used for modern 454 techniques. Does the lasers used for photocleavage of some tags effectively reach all parts of the bead surfaces and emulsion bubbles inside each picotiter plate well? Maybe platinum or reducing agent-based tags require reagents that are too expensive or diffusive poorly into the emulsion bubbles?

3. Other reasons?

It seems like better handling of homopolymers would be a great improvement of 454 sequencing technology. What don’t I know about cleavable 3′ dNTP tag technology which makes it unsuitable for fixing the homopolymer problem?


Rock oil is a complex substance whose fundamental chemistry is still a subject of debate. This fact has energy implications. The time of the petroleome has come.

The T2 explosion and chemical education

In December 2007 an explosion at a chemical plant in Florida killed four and injured 32. Last week C&ENews reported that the Chemical Safety & Hazard Investigation Board (CSB) has released their analysis of the cause of the explosion.

Derek Lowe and his commentariat discuss the accident and some of the issues it has raised. Definitely worth reading.

Molecule of note: lithium nitride

Lithium nitride is a pretty unique substance. (It’s not really a molecule, title of this post not withstanding.)

The wondrous and bedazzling nitride of lithium.

The wondrous and bedazzling nitride of lithium.

It’s formed by the combustion of lithium metal in a nitrogen atmosphere, which is already pretty cool – what else “burns” in pure nitrogen? (Hint: magnesium.) Although a solid, lithium nitride is a fast ion conductor, and is being explored as a solid-phase electrolyte for lithium-ion batteries. Pretty sweet? Check.

The “nitride” anion is powerful enough a base to deprotonate hydrogen gas, forming hydride. This property means lithium nitride (and related materials) could be useful as a H2 storage material if we ever wind up with an H2 economy. Awesome? Check. (That is, lithium nitride is awesome, not an H2 economy.)

And, solutions of lithium nitride in molten alkali chlorides can be used for electrochemical fixation of nitrogen, generating ammonia from atmospheric nitrogen at atmospheric pressure and 300 °C. Compare that to the ~200 atm pressure needed for industrial ammonia synthesis. Pretty sweet? I think so.

Lithium nitride: its that molecule you’ve been hearing about!

What I’m reading

What I’m reading:

  1. The Chemical Tree: A History of Chemistry by William H. Brock. A impressive amount of chemistry, from alchemy to Boyle to Bosch, crammed into a single book. Reading this makes me appreciate just how often and how badly the greats were flat-out wrong about chemistry.
  2. Plows, Plagues, and Petroleum by William F. Ruddiman. The first part of this book distills down what I think is a mainstream view of climatology in a highly readable way. The second part, which I haven’t gotten to yet, seems to be controversial, at least as judged from amazon reviews.