Archive for the 'Science' Category

The Practice of Synthetic Biology

Published March 12, 2010 Science Leave a Comment
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This is the second blog post in my series on Synthetic Biology. My first post was about the promise of synthetic biology (i.e., what makes the field so fascinating). This second post is about the “practice” of synthetic biology (i.e., my experience in toying around with some of the critical tools in the field).

As an unapologetic hacker, I believe the only way you can truly understand a technology is by playing around with it. (MBA’s beware!). By sharing my experiences, I hope people will better understand the revolution that is taking place in synthetic biology– and the implications that has for human health and well-being. So here is my rough guide to getting your feet wet in synthetic biology:

Step 1: Set an objective

One way to think of synthetic biology is that you are programming a microscopic living factory to produce some kind of substance or behavior. So the first step is obviously setting an objective. Do you want your creation to shimmer? To produce butanol? To detect radiation?

The only constraint, aside from your imagination, is that your goal must be attainable using a cell’s biological machinery. In more technical terms, it must be feasible by translating DNA into proteins (which may in turn interact with each other and their environment in complex ways).

Step 2: Select your BioBricks

Recall from my first article that the fundamental tool you will use in synthetic biology is Tom Knight and Drew Endy’s BioBricks, which are “open source” DNA snippets that each have one specific function and can be recombined with each other. The Lego analogy is apt; you create designs by linking together these bricks.

First familiarize yourself with the directory of BioBricks. There are all kinds of bricks, just as there are all kinds legos. There are timers, sensors, switches, reporters, generators, and so forth. Think clearly about what functions you need your bio-machine to perform and read everything you can about the BioBricks necessary to code for those functions. This is very similar to what software engineers need to do when reading the documentation for a standard library or API.

Browsing Documentation of a BioBrick:

Browsing a BioBrick

Step 3: Design a Novel BioBrick (advanced!)

Sometimes, to do something truly interesting, you’ll need to design a brand new BioBrick. This is beyond the scope of this discussion, so let’s defer discussion of this topic. But fear not. Just like you don’t need to know assembly code when writing software code, you don’t really need to know how to design a novel BioBrick to do interesting beginner’s projects in synthetic biology.

Step 4: Synthesize a DNA Fragment

Once you’ve selected your BioBricks and decided how they should be organized (i.e., what order they should be chained in your DNA fragment), it’ll be time to actually synthesize the physical DNA segment. That segment is essentially the “program” that your biological organism will execute.

Start by selecting an online provider who will manufacture the DNA strand for you. In my case, I used a service called Mr. Gene. Using the web, you literally copy and paste your desired DNA sequence into a form. In a few weeks, they send you a little DNA sample that codes your sequence. The process is so insanely simple that it deserves a couple of screen shots.

(Copy…) Reviewing the DNA Sequence of the BioBrick:

Reviewing a BioBrick DNA Sequence

(… And Paste!) Ordering the DNA Sequence Online:

Ordering a DNA Sequence Online

Let’s pause here for a moment and reflect on how mind-blowing this is. Do you need further proof that biology has truly become an information science? Just as it is easy to write computer code, you can now write biological code. You just read some documentation, cut/paste the relevant sequences into a form on the web, and you get the code for a biological machine delivered in the mail.

The cost is relatively low, too. Currently, it only costs 39 cents per base pair. The way the technology is progressing, it won’t be too long before it is only a penny per base pair. Eventually, you may not even need to outsource the synthesis of the DNA fragment. Someday, you’ll be able to buy a little breadbox-size device that’ll let you make DNA at home.

Step 5: Insert DNA into Organism

Okay, given that this is biology, not everything can be done on the computer. The penultimate step requires some “wet” work. You need to take the DNA fragment and insert it into an organism, such as E. coli. None of this is particularly challenging. Most high school biology labs have all the equipment necessary to complete this step– such as pipettes, petri dishes, restriction enzymes, and a few other reagents. After an afternoon of training, anybody can become fluent in the techniques necessary to get novel DNA into bacterial organism.

Step 6: Test, Iterate, and Share!

Due to my background in engineering, I can’t finish this mini-tutorial without insisting that you thoroughly test your creation. Perhaps you will think of ways to tweak your design and improve its functionality. So keep iterating and testing!

In the spirit of the Registry of Standard Parts (and the open source movement), I also insist that you document your creation and share it with the world. You were able to create your machine quickly and easily because of other people’s hard work, so it’s only fair that you contribute back to the community.

Reflections on Revolutions

I wanted to walk you through the entire process of creating a synthetic biological organism in order to illustrate one thing: it is ridiculously simple. The barriers to entry, and therefore the barriers to innovation, have been obliterated.

This is truly the beginning of a revolution. Just as the web revolution enabled a generation of software hackers innovating from their garages, the garage innovators of the next couple of decades will be biology hackers. Who knows what marvelous things are in store?

Endnote: Each time I write about synthetic biology, I can’t help but feel a need to mention the public policy implications. When we hack DNA like this, are we playing God? (My perspective: Yes, but that’s what we humans do whenever we alter the environment.) The more important message to understand is that it will soon not just be academic scientists in laboratories who are “playing God”, but also people in their garages. In the end, with pragmatic regulation, the benefits humanity will see from innovations in synthetic biology will be unquestionably worthwhile.

A Platform for Collaborative Citizen Science

Published March 6, 2010 Science 1 Comment
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I maintain an idea journal that has far more concepts for innovations than I will ever have the time to implement. Rather than letting them gather dust, I’m starting a new series on my blog called “iWant”, which is similar in spirit to Y-Combinator’s RFS. Each installment of “iWant” will describe an idea that I hope someone will pick up and bring into the world.

Please “steal” these ideas. They are provided free of charge, though acknowledgment is always appreciated. As any entrepreneur knows, ideas are a dime a dozen. Hats off to anyone who puts in the sweat and tears necessary to execute any of these concepts!

So without further adieu, here is the first installment of “iWant!”:

Citizen Science

I am downright bullish on the future of “Citizen Science“. For those of you who are unfamiliar with the concept, Citizen Science is a term for describing when ordinary people get together to collaboratively solve scientific challenges. Oftentimes, the people are in geographically disbursed areas and use the internet to coordinate their actions.

The reason I think this is such a promising method of inquiry is that it solves two big problems in one fell swoop:

* Citizen Science breathes new life into the way we learn and teach science.  Too much of science education is based upon learning dry facts as if they were gospel. The true beauty of science lies in observation and experimentation. Collaborative science projects can get kids (and their parents) excited about science again.

* Citizen Science enables an entirely new class of scientific discoveries. Many scientific investigations require a greater volume of data than any one person can collect, or require observations from more locations than any one person can visit. By using a distributed network of people to help out with these experiments, Citizen Science can prevail.

The Vision

I believe that Citizen Science could become a major force in both discovery and education if an online community existed that coordinated this kind of collaborative research. It would be an online platform where each week people could login to see a project on which they could help (kind of like a “Woot for Science”). The website would lead them through the process of how to complete their part of the task. Finally, the platform would facilitate the collection of data from everybody, and assemble it into a single coherent data set that the community could analyze and discuss.

Who knows what discoveries would emerge! Project possibilities are abundant. If there were a critical mass of people who participated, just think of the kinds of science that would suddenly be feasible:

* Entomology. My friend John Forkan imagines the community could create a crowdsourced directory of bugs across the world. Each participant would catalogue a handful of bugs. This would lead not only to an interesting directory, but also interesting maps of where bugs live. Plus, people could compare the kinds of bugs in their location with those of people in other locations, thereby learning about taxonomy and evolution.

* Genetics. With the price of genome sequencing falling exponentially, it may not be long before amateurs can get together and sequence the genomes of almost any creature. Just like the Human Genome Project, each participant would get a small snippet of the DNA. Using a home electrophoresis kit, perhaps they could sequence their small region of the genome. Put them together, and you have the entire genome.

* Astronomy. Amateurs have forever been hunting for comets. But what could you do if you could get thousands of amateurs together for one night? You could choose a small region of the sky, break it up into tiny sectors, and farm out observation of each sector to a participant. When people have spotted a possible comet candidate, they could interact with others in real-time to try to confirm their sightings. How fun would that be to do on Twitter?

I’m sure almost every scientist out there could take an important problem in their field and think of ways to break it down into small pieces that ordinary citizens can help solve.

The Product

To be an effective coordinator of Citizen Science, the online platform would need to facilitate several activities:

* Selection. Each week, the community needs to select a new project on which to collaborate. This could be done by voting, or through an editorial process. To keep focus, at any one time, there should only be one active project on which the community is working.

* Instruction. The service needs to assemble simple instructional materials (ideally a video) to teach people the main concepts they need to know when carrying out their part of the science project. Perhaps even this video could be user-submitted.

* Assignment. The platform needs to make it simple to carve up the project into small chunks and assign them to the right participants. The system should support decomposing projects in several standard ways, such as geographically or temporally.

* Collection. Whether people are uploading videos, contributing pictures, or filling out forms, it needs to be really easy for people to put their data into the system. To start, perhaps the platform could leverage other existing services, such as Google Docs.

* Analysis. This step is the most interesting and requires the most thought. The system needs to help people analyze the contributed data and discuss the implications. Visualization software, statistical tools, and well-moderated forums might well be worth integrating.

The Revenue

Charging for participation in this community would be a non-starter. We’d need as many people as possible to get involved. Therefore, a more promising revenue model is to sell various equipment or kits that participants might need to complete their tasks.

I imagine that most of the projects will require some kind of apparatus. Bird-watching tasks might require binoculars; meteorology tasks might require barometers; microbiology tasks might require petri dishes. Selling these items (either directly or through a Groupon-like referral model) could bring in enough revenue to support the platform.

The Team

I have dispensed with describing the “market” or other details of the economics of this idea because it’s not at all clear that it would be a big opportunity financially. So rather than a scrappy little startup taking this on in order to build a big business, here are a couple of alternative organizations that might instead be well-suited to execute this idea:

* Lab Equipment or Hobby Kit Companies. These organizations could use the platform to promote the sales of their equipment. Since many of them already have relationships with science teachers at schools, they could recruit entire classrooms to be the early participants of the platform. It would be a brilliant complementary service for their existing products. Edmund Scientific and Thames & Kosmos, are you listening?

* Science Museums or University Outreach Offices. These organizations have it in their mission to teach the public about science. As such, they would be perfect to take on the construction of this platform. Through their membership, they already have relationships with science-interested amateurs, who could be the initial participants. I’d love to see the Boston Museum of Science, the American Museum of Natural History, the Exploratorium, or the Maryland Science Center launch this idea!

If you’ve made it this far, I hope you are excited enough to take this idea and run with it. Even if you are a single person and you’re not sure how you could help, just register your interest in the comments. Maybe if enough people chime in, you could form a team to make this idea a reality. I’ll keep my fingers crossed. In the words of Up, “Adventure is Out There!”

The Promise of Synthetic Biology

Published March 5, 2010 Science 1 Comment
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Synthetic Biology is one of the most exciting frontiers of applied science. It aspires to put the “engineering” in the field of genetic engineering. Rather than manipulating DNA in a haphazard manner, synthetic biologists seek to introduce the rigor of engineering to this process. The result, it is hoped, will be the ability to more quickly and more robustly create novel types of biological organisms that can be useful to society.
Want to clean up toxic waste? Why not design a new kind of bacteria that eats the waste and produces fuel? Want to manufacture furniture more simply? Why not design a new kind of tree that grows into the shape of a table? Want to create a more efficient solar panel? Why not redesign plant cells to scale up the process of photosynthesis? The possibilities literally are as boundless as human imagination.
The field is exciting enough that I need to split my thoughts into two posts. This post will provide some background on the field. My next post will detail some of my hands-on experiences.
Pioneers
Two of the pioneers of synthetic biology are Drew Endy and Tom Knight. While Drew Endy’s story has been well-covered in the press, I’ve never met him. But I do know Tom Knight, who is one of the most respected research scientists in MIT’s computer science department. (Incidentally, Tom is the father of James Knight, one of my buddies from undergrad at MIT and every bit as brilliant as his father.)
At about the time I was in my final years of undergrad at MIT (i.e., the turn of the millennium), Tom was in the midst of changing his research focus. He sat in on many of the introductory biology classes and started building a wet lab within the engineering department. As such, he brought an engineer’s perspective to the field of genetics.
Principles
Tom and his collaborators were struck by how inefficient genetic engineering was back in those days. Almost in a one-off manner, researchers would try to assemble from scratch the DNA for new organisms. Tom realized that if he could introduce a few simple engineering principles to this process, he could help the field move much more quickly and robustly.
The most important of those principles was the concept of “interchangeability”. When engineers are designing new devices, they seldom start from scratch. Instead, they use a standard set of interchangeable parts that they can order from catalogs. If you are building a chair, you use standard screws. You don’t design your own screws from scratch. By having a set of standard parts that can be used in conjunction with each other, it is possible build devices faster and more reliably.
Breakthrough Bricks
So that is what Tom Knight and Drew Endy set out to build: a standard set of interchangeable biological parts. Each biological “part” is a DNA sequence that performs one specific useful function, like inverting or measuring signals. To build a biological machine, all you’d need to do is chain together the right parts, just like building Lego creations from those little bricks. They embraced this Lego analogy and called their DNA sequences “BioBricks“.
They could have stopped there, but these guys think big. Rather than designing all of the BioBricks themselves, they wanted to spur massive innovation. So they made their catalog “open source” and allowed anybody to contribute. The result is the Registry of Standard Biological Parts, which at last count contains hundreds, if not thousands, of parts.
What this means is that anybody in the world– even high school students with limited expertise– can apply their creativity in building biological machines. All they need to do is chain together the appropriate BioBricks. If they need a new brick along the way, they can invent one and contribute it to the catalog for all to share. An annual competition, called the International Genetically Engineering Machine competition (iGEM), challenges teams to do exactly that. It has been a smashing success and is growing by leaps and bounds.
Policy Perils
Given the relative ease for amateurs to use the tools of synthetic biology, it is not surprising that the field is raising a few eyebrows in policy circles. People worry that not all of the molecular machines that synthetic biologists design would be so benign. What if a lunatic wanted to engineer a superbug that is capable of inflicting immense harm? Theoretically, the same tools that give rise to helpful synthetic organisms could also give rise to harmful ones.
These concerns are not unwarranted. I expect that in the not too distant future, we will see regulations that aim to curtail the risk of nefarious synthetic biology. Some researchers may be worried that government regulation is likely to have a chilling effect on beneficial innovations in the field. While that is definitely possible, the regulations are likely to be much more favorable so long as researchers start discussing policy solutions immediately. For regulators to make smart decisions, they need to be as educated as possible. And that education must start immediately. The worst thing the field can do is to hide from potential regulation, hoping that it never materializes. Because it is inevitable.
Opportunities
Whenever there is a useful branch of science where the barriers to innovate are collapsing, startups are sure to thrive. If it is not obvious, there are countless billion dollar opportunities for startups in this space. After all, simple bacteria, thanks to their resilience and their propensity to reproduce, are the most efficient factories in the known universe. By reformulating their DNA, you can theoretically “program” them to produce almost any organic substance you want. Synthetic Biology has the promise to revolutionize countless industries, from manufacturing, to agriculture, to energy, to medicine.
The ecosystem for startups to succeed in this burgeoning field couldn’t be more ripe. There is a steady flow of talent streaming out of bioengineering departments. There is more than a critical mass of venture capital firms, like Musea Ventures, targeting this space. And there are hordes of pharmaceuticals, materials, and energy companies impatiently waiting to buy out startups that can demonstrate useful innovations.
My friends, this is the PC industry in the 1970′s! The technology exists in research labs. It is simple and cheap enough that amateur clubs are active. And the markets are well-known. I can’t wait to see what emerges.

“Debating the Science” vs “Debating Science”

Published February 28, 2010 Science 4 Comments
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Thomas Friedman reports that Senator Lindsey Graham has become one of the first Republicans to indicate a willingness to advance climate change legislation. While we should all welcome Senator Graham’s change-of-mind, I am alarmed by his rationale. In essence, Senator Graham is jumping on the climate change bandwagon because he thinks it is good politics, not because he thinks it is sound science. He still maintains that “You can have a genuine debate about the science of climate change….”

Let’s be clear: There is widespread consensus in the scientific community that human activity is catapulting us toward a climate calamity. As such, Senator Graham’s nonchalant dismissal of this consensus are highly irresponsible. Most damaging of all, ordinary citizens hear his words and they start wanting not just to “debate the science”, but rather to “debate science” itself. He gives fodder to those who seek to discredit the entire scientific method.

Just last week, for example, I was walking down the National Mall in D.C. when I overheard two young men discussing how they thought global warming was a complete fallacy. They truly believed that it was a left-wing conspiracy to avenge Al Gore’s loss of the presidency in the 2000 elections. To prove this conclusion, one of the men proudly observed, “Just look at all of the snow D.C. got this year!”

Really, I hold no malice towards my fellow citizens who think that global warming is not real. But hearing those two men dismiss a solid scientific consensus as a conspiracy really got me wondering: despite all the standard science classes they had to take in high school, how could they have such a low opinion of scientific conclusions?

My perspective is that while our nation’s science teachers do an excellent job at teaching the “facts” of science, they need to do a lot better at teaching the philosophy and methods underlying science. In other words, rather than just teach the “what” of science, they need to teach more of the “how”. If they did, more people would understand that science is based upon doubt, not faith. So when scientists reach a consensus, it is not to be taken lightly. And furthermore, it is to be expected that fringe scientists will emerge who think they can shatter the consensus. Although that fringe is almost always dead wrong, they will always exist because success in science is geared towards disproving the current dogma. Sadly, most climate change deniers just don’t understand that science works this way.

Most of us fluent in science forget that as a philosophy, science is radically different than most other realms of human epistemology. Religion, for example, is not based upon doubt. It is based upon faith. So when science is taught as a series of facts rather than a methodology, people can’t see how it is any different from religion. They expect scientists to be “priests” revealing the truth. And when they read reports of debate within the scientific community, they think scientists are in a confused state of disarray. They lose their “faith” in science, when in fact it is operating perfectly.

Therefore, I close with a simple message for Senator Graham: I’m glad that you are helping to advance meaningful legislation to solve the climate crisis. But while you are at it, also be sure to also double down on federal funding of science education. Scientific debate is too important to America’s future to let the existence of those debates erode the public’s respect for science itself.

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