Tom Knight, Godfather Of Synthetic Biology, On How To Learn Something New

It was partly frustration with designing silicon chips that led Tom Knight to the study of biology. A senior research scientist at MITs Computer Science and Artificial Intelligence Laboratory, Knight started working in MITs AI Lab while he was in high school. As an MIT student and faculty member, in the 60s and 70s Knight was a co-engineer of ARPANET, a precursor of the Internet, and helped design the first commercial single-user computer workstations, eventually earning more than 30 patents for his work in computer science and electrical engineering. In the 1990s, Knight became fascinated with biology, went back to school, and set up a molecular biology lab within MITs computer science lab. There, Knight invented BioBricks--standardized DNA parts that make up a kind of free operating system for biotechnology. For his pioneering work merging concepts from engineering and biology, Knight is widely considered the godfather of the emerging science of synthetic biology. Here, this key player in the technological revolution of the last century talks about biology as this centurys defining technology, the need for scientific generalists, and the best way to learn something new.

FAST COMPANY: Internet legend has it that you started at MIT when you were 14? TOM KNIGHT: Well, that story has gotten a little overblown. I entered as a regular undergrad at the normal time. But I was a local boy--I grew up in Wakefield, Massachusetts--and I spent a lot of my high school years at MIT, taking courses in computer programming and organic chemistry, and I spent my junior and senior summers working at the artificial intelligence lab there.

So, did you study computer engineering as an undergrad? You couldnt really study computer science then--it was the bastard child of electrical engineering. This was the dawn of the artificial intelligence world at that point, and people had only been working on it for five years or so.

Did you go directly into a grad school? I took a fair amount of time off, working as a research staff member at MIT from 1969 to 1978, partly because I could get a draft deferment. During that time, I did a lot of hardware and software work having to do with operating systems, hardware maintenance, and the construction of new computers. One of the important things I helped develop was a time-sharing system called ITS that now nobody knows about, which was oriented to making users as productive as possible. Its hard to remember how bad computers were at that time--we struggled mightily to get computers that had a megabyte of core storage. Another important thing we worked on in that period of the late '60s, early '70s, was interfacing with ARPANET, which later became the NSF Net, and later the Internet. We also designed one of the first bitmap-oriented printers, which was made obsolete when laser printers came along.

Were you making money from any of this? My masters thesis when I went back to grad school in 1978 was building a computer to more efficiently run the Lisp programming language, which I worked on with my MIT colleague Richard Greenblatt. That eventually resulted in the formation of spinout companies--unfortunately two instead of one. Greenblatt and I did not see eye to eye about how to commercialize the technology, so he started Lisp Machines, and I and a number of others started our own company called Symbolics [symbolics.com was the first registered .com domain name]. Both companies were successful--Symbolics went public and resulted in several thousand machines being distributed.

How did you get into biology from computing? In the 1980s, I learned how to engineer integrated circuits, and as part of my PhD thesis, I designed one of the first silicon retinas. Looking at Moores Law, which predicts the path of technology in silicon, by 1990 I could predict that at some point--which is right about now--you wouldnt be able to do the magical shrinking act anymore [of fitting more and more transistors on an integrated circuit]. The number of atoms across the transistor becomes too small. Were now down to the 22 nanometer range, and another shrink will bring that down to 10 nanometers. Thats only about 60 atoms across. If you shrink that another factor, you have 10 or 12 atoms. The way silicon manufacturing works, you put things in place statistically, randomly. At this size, chances are youre not going to be able to get things in the right place anymore. It was clear that we needed a different way of putting atoms in the right place. There is a technology for putting atoms where you want them--its called chemistry. You design a molecule, and that has the atoms where you want them. Whats the most sophisticated kind of chemistry? Its biochemistry. I imagined that you could use bio-molecules like proteins that have the ability to self-assemble and crystallize in the range you needed.

So, you were hoping that biology could help you better engineer silicon chips? Yes, that was part of what got me interested in biology. Something else that really changed my thinking was a proposal by a physicist-turned-biologist names Harold Morowitz called A Complete Understanding of Life. How can you not like something like that! His basic proposal was that we have all this advanced technology--if we put our minds to it and applied all this technology, we could actually understand how simple organisms work. My general bias toward biology at that point was, Oh my god, its so complicated, well never figure out whats going on--in contrast to something like computers where you can understand everything. It was really quite amazing to see somebody proposing what Id assumed was impossible. I got quite intrigued by the idea that I could go and do something with biology.

But you were no expert on biology--how did you get up to speed? Starting in 1990 or so, I started seriously looking at classical biology books, with a strong concentration on simple organisms. I started taking the graduate core courses in biology at MIT and basically became a student. It was challenging but very effective for educating myself. In 1995, along with one of my students, I took the sophomore undergraduate intro to molecular biology class--that was fun, learning how to pipette and work in the lab.

Do you have any study tips for other people who are trying to learn a new subject? I like to read books, three or four at a time. I rarely read books all the way through. Ill get a few books on a subject--you want single-author books, someone with a well-defined point of view--and read a section, and then switch to a different book and read about the same thing. I keep switching back and forth--its a great technique because you get to look at the same subject from many peoples perspective. That turns out to be actually really useful.

How did your outsider's perspective as a computer engineer inform your approach to biology? After setting up a molecular biology lab in the computer science department at MIT, it became clear to me that I didnt want to do plumbing in the way biology had been doing it for two decades. My basic realization was that every time I wanted to do one experiment, it was actually two experiments: 1. the experiment I wanted to do, and 2. building the piece of DNA I wanted. The second experiment was not that intellectually interesting, and it wasnt publishable. It just became annoying. The question was, how do you get rid of that?

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Tom Knight, Godfather Of Synthetic Biology, On How To Learn Something New

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