One of the many features of DNA is that it responds to signals over time. It interacts with molecules and enzymes in the cell which often tell it to do something later, after it has received several other chemical signals - or to react instantly when in the presence of certain proteins. The fact that DNA responds predictably to certain signals means that it could be turned into a counter that measures time via regularly delivered molecular signals. So if you built a biological machine that needed to count particulate matter in the air, DNA would be the perfect mechanism to use. Just a reengineer it to emit a particular protein after it had encountered, say, 10 particles of a toxin - then create a device that rings a bell when it sees the protein. Poof - you've got a biological machine that rings a bell when dangerous toxins are in the air.

Stanford synthetic biologist Christina D. Smolke described the importance of this new study in Science to us via e-mail:

A counter will allow you to program function or trigger responses based on frequencies of detected events over time (and therefore are an important component of programming in time and space). One of the more immediate applications would be trigger an event in response to a certain number of cell divisions or cell cycles. For instance, if there were a molecule associated with a certain phase of the cell cycle one could 'count' that molecule over time and therefore count the number of cell cycles. In this case, one might want to trigger cell death after a certain number of cell cycles as a means to avoid uncontrolled cell growth (or cancer)... You can also imagine wanting to detect not just the concentration of an environmental contaminant, but also its frequency of occurrence over time. Other technologies could use this as a safety kill switch, such that if one is releasing an engineered microorganism into the environment, you could use this counter to trigger its death after a certain number of cell divisions to provide better control over the engineered system and less chance for spreading from the intended application.

Most of the applications for this biotechnology are in medicine, but as Smolke points out you really could build a toxin sensor, or even a cell that is programmed to die after a set amount of time.

You can read Smolke's entire article in Science, and you can read the study she described in the same issue.

Congratulations to Slovenia , who took the grand prize BioBrick trophy home with them with their project, which was designed to create a vaccine for H. pylori, infection with which is associated with ulcers and gastric cancer. H. pylori possesses "stealth flagella", which manage to avoid an important immune receptor. Slovenia attempted to combine bits of other bacterial proteins (that aren't capable of avoiding that receptor) with bits of H. pylori proteins in an attempt to hand-feed H. pylori antigen targets to the immune system, with promising results.

Frieburg took second place by combining DNA origami (the animation is borrowed from their wiki) with a clever receptor scheme in order to attempt nanoscale control of cellular signaling.

This DNA origami basically takes a long piece of DNA and, by adding many short carefully chosen DNA tethers designed to bind to the longer DNA in specific places, fold it into a particular shape.

Third place went to Caltech's multifunctional probiotic bacteria by adding functions to a commercially available, non-pathogenic probiotic strain of E. coli - functions including pathogen defense, vitamin production, and a treatment for lactose intolerance. (Bioengineered bacteria - digesting lactose so you don't have to.) Probiotics were big at iGEM this year, with MIT taking a probiotic approach to dental care and finalist NYMU-Taipei's BactoKidney - a bacteria that attaches to the wall of your small intestine, then munches on waste products before abandoning ship before it overstays its welcome.

The image is from NYMU-Taipei's wiki, where you can see its full-resolution glory. Trust me, dialysis isn't nearly so adorable.

UC Berkeley didn't do so bad either - we had two teams, one devoted to a wet lab project to combine engineered bacteria with robots, making large-scale synthetic biology projects possible, and the other working on computational tools to keep better track and make better use of collections of genetic parts. Our wet team, CloneBots, made it to the finals, and our comp team, Clotho, won for best software tool.

This year was my first jamboree, and I was gobsmacked at the collective hard work and ingenuity on display. Anyone who does research knows how difficult it is to accomplish a significant amount of work in a single semester, but these teams went at their projects with energy and intensity, and it shows.

Congratulations, everyone! We hope to see you in 2009. If iGEM or our mad science contest sound like your idea of a good time, see if your university has an iGEM team. If not, it's time to start one.

On a more somber note, this is going to be my last Ask a Biogeek - professional obligations abound. If I didn't have a chance to get to your question yet, apologies. A few of those obligations may be of interest to y'all, so keep an ear to the ground and you may be hearing from me again soon. Take care!

In an article published with Win and Smolke's research in the October 17 issue of Science, Ehud Shapiro and Binyamin Gil describe the unique difficulties facing synthetic biologists:

The challenges of biomolecular computer engineering are best illustrated by comparing them to those of electronic computer engineering. In the latter, one can conceive of an advanced and innovative computer design, use one's favorite computer-aided design software, send the design to a chip fabrication facility, and with luck have a working electronic device in short order. In the field of biomolecular computers, one can equally dream of innovative designs that can be made, in principle, from known protein building blocks. However, protein engineering is in infancy compared to electronic circuit engineering. There is no protein design software to turn to, and no fabrication facility that can engineer a protein to a specification of its function. Therefore, researchers cannot construct their own advanced protein machinery and must make do with DNA, RNA, or naturally available proteins.

Win and Smolke made do with RNA, and the results are spectacular.

Their experiment began with the determination of three main components: a sensor, an actuator, and a transmitter, each a different type of short RNA molecule. Using these three components, Win and Smolke created RNA devices that take in a molecular input and translate that to an output of a certain gene expression. In effect, these RNA devices act as internal gates within the cell. By combining these internal gates in different ways, Win and Smolke constructed logical operations within the cell that programmed for the production of certain proteins.

The result is a logical system that can take in two different inputs — theophylline and tetracycline — and produce a corresponding output — in this case, the Nobel-Prize-winning green fluorescent protein (GFP). Programmed to mimic an AND gate, the cell produces GFP only when both theophylline and tetracycline are present. Conversely, programmed as an NOR gate, the cell produces GFP only when both theophylline and tetracycline are not present. Programmed as an NAND gate, the cell produces GFP in every case but the one where theophylline and tetracycline are both present. Basic Boolean algebra meets bioengineering, and now we can order our cells around just like we do our computers.

Win and Smolke's system is the first that can take in multiple inputs, which is an amazing advantage for would-be biological programmers. It's also very flexible and easy to program; scientists can treat it as a "plug-and-play" framework, in which it's easy to keep changing the components of the RNA device to allow for an infinite number of computations. And the best news is that though Win and Smolke published only the results they got from testing in yeast cells, they say that their devices will translate to mammal cells with no trouble. Your cells could soon be detecting tumors or conducting their own targeted gene therapy to fight cancer — and this at a molecular level, all under the direction of scientific and medical professionals. Sounds good to me.

Caltech Engineers Build First-Ever Multi-Input "Plug-and-Play" Synthetic RNA Device [Caltech]
Higher-Order Cellular Information Processing with Synthetic RNA Devices [Science]
RNA Computing in a Living Cell [Science]

Images from Science.

The winners in our two categories will get either an all-expenses-paid trip to the kickass Synthetic Biology Conference in Hong Kong this October, or $1000 and a chance to have their creature drawn by a cool comic book artist. Find out more below.

There are two categories in the contest, each with their own prize. The important thing to remember is that this contest is about creating cool new lifeforms that are also, in some way, entertaining. So each entry will be judged for plausibility (i.e. whether it is scientifically justifiable), creativity, usefulness, and entertainment value.

Our esteemed judges include synthetic biologist Drew Endy (MIT), evolutionary biologist and PLoS co-founder Michael Eisen (UC Berkeley), Spore game developer Jason Shankel (EA/Maxis), and biology researcher/io9 "ask a biogeek" columnist Terry Johnson (UC Berkeley).

Category One: BioBricks Lifeform
Using the BioBricks registry of standard biological parts, propose a lifeform design that you could conceivably create in a lab. Must include a complete description of how you would make the lifeform, what it would do, and what possible hazards might be involved in creating it. You may design this creature with a team, but only one of you can claim the prize. You may enter lifeforms that you have entered in other contests, but you must state in your entry which contest(s) you've already entered. Your entry should be in the form of a short scientific paper (no more than 3000 words), with illustrations. More points given if you've actually got a working organism.
Prize: All travel and hotel expenses paid trip to the Synthetic Biology Conference in Hong Kong in October, as well as the chance to present your research there.

Category Two: General Synthetic Lifeform
This lifeform can be more creative. Propose a scientifically justifiable lifeform, which could conceivably be created using current technology. Explain how you would create it, what it would do, and hazards involved. Unlike the BioBricks lifeform, this lifeform can be more speculative. It should be science fictional, but must remain scientifically plausible. Your entry should be less than 3,000 words, please. Illustrations and diagrams are a good idea.
Prize: $1000, plus a cool comic book artist will draw your lifeform and you'll get a signed copy of the original art.

DEADLINE FOR ALL ENTRIES IS AUGUST 25 AT MIDNIGHT PST.

General Rules

1. Send queries and completed entries to madscience@io9.com.
2. On entries, please include your full name, an email and phone number where we can reach you, plus any information about other contests you may have entered your lifeform in.
3. Winners will be announced September 8.
4. All general Gawker contest rules apply.

The winners in our two categories will get either an all-expenses-paid trip to the kickass Synthetic Biology Conference in Hong Kong this October, or $1000 and a chance to have their creature drawn by a cool comic book artist. Find out more below.

There are two categories in the contest, each with their own prize. The important thing to remember is that this contest is about creating cool new lifeforms that are also, in some way, entertaining. So each entry will be judged for plausibility (i.e. whether it is scientifically justifiable), creativity, usefulness, and entertainment value.

Our esteemed judges include synthetic biologist Drew Endy (MIT), evolutionary biologist and PLoS co-founder Michael Eisen (UC Berkeley), Spore game developer Jason Shankel (EA/Maxis), and biology researcher/io9 "ask a biogeek" columnist Terry Johnson (UC Berkeley).

Category One: BioBricks Lifeform
Using the BioBricks registry of standard biological parts, propose a lifeform design that you could conceivably create in a lab. Must include a complete description of how you would make the lifeform, what it would do, and what possible hazards might be involved in creating it. You may design this creature with a team, but only one of you can claim the prize. You may enter lifeforms that you have entered in other contests, but you must state in your entry which contest(s) you've already entered. Your entry should be in the form of a short scientific paper (no more than 3000 words), with illustrations. More points given if you've actually got a working organism.
Prize: All travel and hotel expenses paid trip to the Synthetic Biology Conference in Hong Kong in October, as well as the chance to present your research there.

Category Two: General Synthetic Lifeform
This lifeform can be more creative. Propose a scientifically justifiable lifeform, which could conceivably be created using current technology. Explain how you would create it, what it would do, and hazards involved. Unlike the BioBricks lifeform, this lifeform can be more speculative. It should be science fictional, but must remain scientifically plausible. Your entry should be less than 3,000 words, please. Illustrations and diagrams are a good idea.
Prize: $1000, plus a cool comic book artist will draw your lifeform and you'll get a signed copy of the original art.

DEADLINE FOR ALL ENTRIES IS AUGUST 25 AT MIDNIGHT PST.

General Rules

1. Send queries and completed entries to madscience@io9.com.
2. On entries, please include your full name, an email and phone number where we can reach you, plus any information about other contests you may have entered your lifeform in.
3. Winners will be announced September 8.
4. All general Gawker contest rules apply.

There are two categories in the contest, each with their own prize. The important thing to remember is that this contest is about creating cool new lifeforms that are also, in some way, entertaining. So each entry will be judged for plausibility (i.e. whether it is scientifically justifiable), creativity, usefulness, and entertainment value.

Our esteemed judges include synthetic biologist Drew Endy (MIT), evolutionary biologist and PLoS co-founder Michael Eisen (UC Berkeley), Spore game developer Jason Shankel (EA/Maxis), and biology researcher/io9 "ask a biogeek" columnist Terry Johnson (UC Berkeley).

Category One: BioBricks Lifeform
Using the BioBricks registry of standard biological parts, propose a lifeform design that you could conceivably create in a lab. Must include a complete description of how you would make the lifeform, what it would do, and what possible hazards might be involved in creating it. You may design this creature with a team, but only one of you can claim the prize. You may enter lifeforms that you have entered in other contests, but you must state in your entry which contest(s) you've already entered. Your entry should be in the form of a short scientific paper (no more than 3000 words), with illustrations. More points given if you've actually got a working organism.
Prize: All travel and hotel expenses paid trip to the Synthetic Biology Conference in Hong Kong in October, as well as the chance to present your research there.

Category Two: General Synthetic Lifeform
This lifeform can be more creative. Propose a scientifically justifiable lifeform, which could conceivably be created using current technology. Explain how you would create it, what it would do, and hazards involved. Unlike the BioBricks lifeform, this lifeform can be more speculative. It should be science fictional, but must remain scientifically plausible. Your entry should be less than 3,000 words, please. Illustrations and diagrams are a good idea.
Prize: $1000, plus a cool comic book artist will draw your lifeform and you'll get a signed copy of the original art.

DEADLINE FOR ALL ENTRIES IS AUGUST 25 AT MIDNIGHT PST.

General Rules

1. Send queries and completed entries to madscience@io9.com.
2. On entries, please include your full name, an email and phone number where we can reach you, plus any information about other contests you may have entered your lifeform in.
3. Winners will be announced September 8.
4. All general Gawker contest rules apply.

As a biologist who studies whole organisms and populations, I find that more and more of biology (in terms of funding, positions and emphasis) is going to the sub-organismal level. We now have lots of cell biologists, geneticists, neurologists, biochemists, biomechanics, bioengineers and so on, but not a lot of behaviorists, population ecologists, biodemographers and others who study the emergent properties that arise at the higher levels of organization. What role, if any, do you foresee for understanding of these higher level biological phenomena in the future sci-fi-ish stuff?

As far as emerging biotechnology goes, science fiction grapples more frequently (if not always very seriously) with issues of organismal or ecological impact than the scientific establishment. There are good reasons for this. Ecological ruminations are a tradition for the authors, and the scientists have - until quite recently - been limited by technical considerations. As a scientist, I hope the title Planetary Ecologist will go on someone's tax return someday.

A Sandworm of Arrakis, from Frank Herbert's Dune.

Some would say that Frank Herbert's Dune was the beginning of ecological science fiction, but its roots go much deeper than that. Every time an author has imagined an alien world and then tried to fill it with beings capable of surviving on it, that author is grappling with issues of ecology, and every time an author has decided how those aliens would act, they were engaging in a bit of recreational behaviorism. Herbert elevated the tone and raised the bar, no doubt, but there is a long-standing tradition of biological and behavioral what-if in SF. The rise of environmentalism coupled with another favorite SF theme - dystopianism - brought us the environmental disaster subgenre, from the ridiculous The Day After Tomorrow to more thoughtful treatments like David Brin's Earth or the works of Kim Stanley Robinson.

Mars (with a little terraforming and a lot of luck).

While there are (of course) ecologists in the scientific community, there are very few thus far that bridge the gap between research at the molecular level and ecologies larger than a tissue culture dish. This is not to imply that ecologists are ignorant of molecular biology; the field has generated far too many useful tools for that. The bioengineers and cell biologists who are designing new organisms at the molecular level, on the other hand, are not always well versed in the basics of ecology and evolution. They are necessarily focused on what one scientist has called the molecular sociology of the cell.

Up until quite recently it would have been ludicrous to expect a molecular biologist to consider the higher-level environmental interactions of, for example, a particular gene, because he or she was still trying to figure out (at a molecular level) what the damn gene did to the cell itself. Take a peek at the inner life of a cell (if you haven't seen if before). A single cell is a giant bag of confusion. Trying to sort out web of interactions between the thousands of molecules present in hundreds of compartments using the technology at hand has been compared to figuring out the rules for a game of football using only pictures of the field (that only show certain players) at various times. This is why many researchers like to work with single cells instead of a cell in its natural environment, whatever that is - the cell alone is complicated enough. Experimental limitations or therapeutic concerns often require an intimate knowledge of a single organism's physiology, effectively tying a researcher to a single animal. Heinlein said, "Specialization is for insects". I would add grad students to the list.

Take E. coli as an example. We've had its genome sequenced for over a decade. Type its name into Google Scholar and you'll find over 1.5 million hits. Yet programming this bacteria - synthetic biology - is still a difficult and time-consuming process. When The University of Texas at Austin's entered their light-sensitive pigment-producing bacteria biofilm in the intercollegiate Genetically Engineered Machine (iGEM) contest, they realized that their achievement barely scratched the surface - that the "program" they'd written into the bacteria was relatively simple compared to the programming it already used to survive. In recognition of this fact, they produced perhaps my favorite "Hello world" program ever.

10 GOTO e. coli 20 Hack it genetically to turn it into a light-sensitive film

It's also important to note that almost all of the engineered cells and organisms made today are never meant to be released in the environment (and wouldn't be likely to survive in it if they did). Those that aren't created purely for research purposes are typically meant to live in small, artificial, and easily replaceable ecologies, like bioreactors in a pharmaceutical company or fermenters in a winery.

Either the bacteria are doing what they've been programmed to or we have a serious Cthulhu problem.

Genetically modified foods are a special case, but as a special case they've already received the most attention by ecologists. GM organisms that are designed to move outside of the lab enter the purview of the ecologists.

While disciplines like bioinformatics combine computational and molecular biology with evolutionary studies, increasingly complicated bioengineered organisms designed for the wild will require the ability to effectively model the ecologies they were designed for. In brief, once we're good enough at figuring out how to make a cell jump or play dead, the next frontier of design will be figuring out when we want a cell to jump or play dead, considering its surroundings. Top image via Electro-Plankton.

Do you have questions you've always wanted to ask a biogeek? You can email me at tdj@io9.com.

Registry of Standard Biological Parts [a wiki]. Start with the tutorial, just to get a flavor of what it means to take standard biological parts from a registry and put them together into a new organism. It's actually a lot simpler than you might think. This parts registry is a tool repository, but also a repository of information about biological parts that people have standarized, codified, and registered. A "part" isn't something like an arm — it's going to be something small, like an enzyme that affects a gene, or a protein that causes a particular biological state. Or perhaps a gene that will make you grow an arm.

Open Wetware Project [a community]. This is a clearinghouse community site for academics, students, and the public to share information about synthetic biology and biological engineering projects. You'll find classes, tutorials, and massive lists of laboratories working on biohacking. It's a great place to poke around and find out what people are really doing to create new life forms — and what their motivations are. Also, if you've got your own project or want to know more about an ongoing project, this the place to go to share ideas.

Programming DNA [a lecture] As we've mentioned before, MIT professor Drew Endy gave a smashing and fun introductory lecture about biohacking a couple of months ago at the Chaos Computer Congress in Berlin. If you want a crash course in how hacking a biological system can be like hacking a machine, load this one into your portable media device of choice and watch it during your commute (but only if you're not driving).

BioBricks Foundation [a standards body]. This is a non-profit formed by people from Harvard, MIT and UCSF in order to create standards for what counts as a "biological part." They're tackling legal and ethical issues, as well as strongly supporting the idea of making all information about biological parts and synthetic biology available for free to the public.

Open Biohacking Kit [via Sourceforge]. Get started on your biohacking project with this free software package. From the Sourceforge description:

This open, free synthetic biology kit contains all sorts of information from across the web on how to do it: how to extract and amplify DNA, cloning techniques, making DNA by what's known as oligonucleotides, and all sorts of other tutorials and documents on techniques in genetic engineering, tissue engineering, synbio (synthetic biology), stem cell research, SCNT, evolutionary engineering, bioinformatics, etc.

Image above is of a creature created with Maxis' forthcoming game Spore.