Virtual biology: Computer worms; A crowd-funded project aims to build the world’s first simulated organism

Virtual biology: Computer worms; A crowd-funded project aims to build the world’s first simulated organism

May 24th 2014 | From the print edition

ANY scientist will tell you that most of the work which gets done at the conferences they attend happens not in the lecture halls but around the coffee machines outside them (not to mention in the bars that delegates repair to after the lectures are finished). That is where ideas are swapped, phone numbers exchanged and collaborations begun.

One of the undersold boons of the internet is that it functions a bit like a permanent, rolling global coffee break. A good example of the result is OpenWorm, an informal collaboration of biologists and computer scientists from America, Britain, Russia and elsewhere. On May 19th this group managed to raise $121,076 on Kickstarter, a crowd-funding website. The money will be put towards the creation of the world’s most detailed virtual life form—an accurate, open-source, digital clone of a critter called Caenorhabditis elegans, a 1mm-long nematode that lives in the soils of the world’s temperate regions.

C. elegans is a scientific stalwart. It is simple, transparent, easy to feed and easy to breed. As a result it is one of the best-understood organisms in biology. Hermaphrodite individuals (which is most of them) have exactly 959 cells, of which 302 are neurons. The location and the function of every one of these cells is known. Thanks to work begun in the 1970s, scientists even have a complete map—a “connectome”—of how the neurons link up with each other to form the worm’s nervous system. Despite 40 years of technological progress, C. elegans remains the only animal for which such a diagram is available.

It is detailed information like this that makes OpenWorm possible. There are two ways to build a model: from the top down or from the bottom up. The top-down method is easier. Instead of worrying about how the thing being modelled works, you need only find some equations that reproduce its behaviour; economic models often work this way. It would be possible, for example, to model the snakelike locomotion of C. elegans using high-school mathematics. But that would not be very illuminating.

OpenWorm therefore proceeds in the other direction. The idea, says Stephen Larson, a neuro- and computer scientist, who is the project’s co-ordinator, is to model the biochemical behaviour of every one of the worm’s cells, and how they interact with each other. If that can be done, then movement—and all the beast’s other behaviour patterns—should emerge by themselves from that mass of interactions.

Building a complete electronic organism in this way, one that aims to be functionally indistinguishable from its fleshy counterpart, would be quite an achievement. It would also be useful. The human brain, for instance, differs from the worm’s tiny nervous system only in the number and interconnectedness of its neurons. But although plenty of cash and brow-sweat have been thrown at the problem over the years, nobody really knows how the brain works. Having a detailed, proddable model of a far simpler nervous system would be a good first step. And C. elegans is already used to probe everything from basic biochemistry to the actions of drugs in laboratories. The ability to run those tests electronically, with no need for actual worms, and to be reasonably sure that the results will nonetheless be the same as in the real world, would be a boon to biological and medical research.

Details, details

For now, no one is quite clear what a faithful simulation would look like. The point of a model is to remove unnecessary, cluttering details, while preserving the essence of whatever it is the model-maker wants to study. But even for an organism as well-researched as C. elegans, no one is sure which details are crucial and which extraneous. A living cell is a complicated mess of enzymes, ion channels, messenger molecules and voltages. Attempting to simulate everything faithfully would bring even a supercomputer to its knees.

For the moment, the team is planning systems that will simulate how the worm’s muscle cells work, how its neurons behave and how electrical impulses move from one to the other. There will be physics algorithms that give the worm a realistic simulation of a Petri dish to move through. They will also make sure its virtual muscles can deform its virtual body by the correct amount when they receive a virtual jolt from a virtual neuron.

The results will be compared with reality, in the form of a database of about 12,000 videos of how C. elegans behaves in the real world. The more kinds of behaviour the electronic worm can accurately reproduce, the better it will be. Crucially, says Matteo Cantarelli, another of the project’s founders, the system is designed to be flexible and easy to tweak. That lets the team improve it on the fly, either through subtle changes to what is already there, or by adding completely new chunks of code. For instance, proteins can diffuse through the worm, and change aspects of its behaviour when they do so. OpenWorm cannot model that at present, but the team has plans to make it do so.

This flexibility also allows the researchers to modify their model as science advances. On May 18th a group from the Massachusetts Institute of Technology and the University of Vienna published in Nature Methods a way to scan the nervous system of a live C. elegansin real time. That adds crucial data. If a connectome is like a road map, the ability to watch its neurons firing is like getting satellite video that shows how traffic is flowing along the map’s roads: which are busy (and when), and which are rarely travelled. The OpenWorm team is already keen to integrate these data into its model.

As its name suggests, OpenWorm is available to anyone to play with. And its success on Kickstarter may help raise interest—and cash—from elsewhere. “We’ve thought about applying for traditional grants,” says Dr Larson. “And the success of this crowd-funding proves that there’s public interest in this, which ought to help our case.” If he and his collaborators succeed in their ambitions, then doing biological research may one day become a simple matter of downloading some animals onto your computer, and getting started.

 

About bambooinnovator
Kee Koon Boon (“KB”) is the co-founder and director of HERO Investment Management which provides specialized fund management and investment advisory services to the ARCHEA Asia HERO Innovators Fund (www.heroinnovator.com), the only Asian SMID-cap tech-focused fund in the industry. KB is an internationally featured investor rooted in the principles of value investing for over a decade as a fund manager and analyst in the Asian capital markets who started his career at a boutique hedge fund in Singapore where he was with the firm since 2002 and was also part of the core investment committee in significantly outperforming the index in the 10-year-plus-old flagship Asian fund. He was also the portfolio manager for Asia-Pacific equities at Korea’s largest mutual fund company. Prior to setting up the H.E.R.O. Innovators Fund, KB was the Chief Investment Officer & CEO of a Singapore Registered Fund Management Company (RFMC) where he is responsible for listed Asian equity investments. KB had taught accounting at the Singapore Management University (SMU) as a faculty member and also pioneered the 15-week course on Accounting Fraud in Asia as an official module at SMU. KB remains grateful and honored to be invited by Singapore’s financial regulator Monetary Authority of Singapore (MAS) to present to their top management team about implementing a world’s first fact-based forward-looking fraud detection framework to bring about benefits for the capital markets in Singapore and for the public and investment community. KB also served the community in sharing his insights in writing articles about value investing and corporate governance in the media that include Business Times, Straits Times, Jakarta Post, Manual of Ideas, Investopedia, TedXWallStreet. He had also presented in top investment, banking and finance conferences in America, Italy, Sydney, Cape Town, HK, China. He has trained CEOs, entrepreneurs, CFOs, management executives in business strategy & business model innovation in Singapore, HK and China.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: