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Probiotics, a field that seeks to use edible bacteria to improve human health, may soon undergo a metamorphosis. Students at MIT and Caltech are using the techniques of synthetic biology to create bacteria that fight cavities, produce vitamins, and treat lactose intolerance, as part of the International Genetically Engineered Machines (iGEM) competition at MIT. The new research might lead to a cheaper way to produce medicines or improve diets in the developing world.

Synthetic biology is the quest to design and build novel organisms that perform useful functions. Much research in the field has concentrated on using bacteria as a factory: one of its early successes was the development of microbes that produce malaria medicine. Other research has investigated targeted delivery vehicles, such as microbes engineered to bring medicine to a specific part of the body. But the new projects are attempts to enhance the health benefits of edible bacteria.

These projects capitalize on the fact that our bodies are already colonized by billions of bacteria. “If you really want to apply a bacterium to a person, think about where they naturally exist and survive in a human while still trying to engineer new functions,” says Christina Smolke, a synthetic biologist at Caltech who advises the university’s team.

Our mouths, for example, are a haven to bacteria, both good and bad. Bacteria that live in the dental plaque, called Streptococcus mutans, feed off of sugar on our teeth and then excrete acids, which wear away dental enamel and cause cavities. To create cavity-fighting microbes, the MIT team started with a peptide–a short protein segment–that has been previously shown to prevent the bad bacteria from sticking to the teeth. The team built a piece of DNA containing both the gene that makes the peptide and a gene for a molecular signal that causes the bacterium to excrete it.

The next step will be to insert this piece of DNA into Lactobacillus bulgaricus, a microbe common in yogurt. The students haven’t done that yet, but they have successfully introduced foreign DNA into the microbe, which primes the microbe for further genetic engineering. That in itself is an impressive feat, given that Lactobacillus bulgaricus is not commonly used in the lab and thus requires development of new experimental techniques.

If the microbe can be successfully engineered, eating yogurt would deposit it on the teeth, where it would produce the protective peptide. “This would probably be more effective than an antibacterial that kills everything,” says Chia-Yung Wu, a biology graduate student at MIT who advises the team. “It just targets the harmful stuff.” (A common problem with antibiotics is that they kill both harmful and helpful bacteria in the mouth and gut, leaving an open landscape for bad bacteria to colonize.)

One central project in synthetic biology is the attempt to create a huge, publicly accessible “parts list,” a catalogue of gene sequences and the functions of the resulting proteins. The MIT team doesn’t intend to develop a product for commercial use, but the biological parts that it creates might one day be used in other applications–enhancing the nutritional value of yogurt, for example, with bacteria that produce a specific type of vitamin. The team, which includes undergrads Sara Mouradian and Derek Ju, has already deposited the parts that it’s created in a central repository at MIT called the Registry of Standard Biological Parts. Expanding the registry is one of the most important aspects of the competition. “This year, we sent out 2,000 DNA parts to each team, and we’re getting back 1,500 new parts,” says Randy Rettberg, iGEM director and a principal research scientist at MIT.

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Credit: Utah State University
Video by Emily Singer, images courtesy MIT, video edited by Brittany Sauser.

Tagged: Computing, Biomedicine, MIT, bacteria, health, synthetic biology

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