08 Nov 2016 A spoonful of GM bacteria
Would you swallow a dose of genetically engineered bacteria? Synthetic biologists developing ways to deliver modified bacteria as therapeutics via the gut certainly hope so.
Sometime next year, volunteers in the US could start swallowing capsules stuffed with genetically engineered E coli.
The experimental pills, designed by Synlogic, a Cambridge, Massachusetts, synthetic biology startup, contain bacteria designed to treat a rare metabolic disease by recognising when they reach a person’s stomach and then soaking up large amounts of ammonia.
The treatment, slated for its first clinical test during 2017, is an early example of what the company’s founders call “synthetic biotics” — or intestinal bacteria endowed with genetic programs that allow them to sense something going on in the body and then take an action, like deliver a drug or release a coloured chemical useful in a diagnostic test.
The idea of swallowing GM bacteria might seem odd. But purpose-built germs could be a new way to take over physiological functions that people’s own bodies can’t perform if they are sick, and a substitute for pills or injections.
The smart bacteria could be the first medical use of a form of synthetic biology popularised by Synlogic cofounder and MIT professor, James Collins, starting in 2000.
That year, Collins, taking his cue from electronics, constructed what’s essentially a toggle switch in E coli — a circuit involving two genes that could flip-flop between states. It was nifty demonstration, and soon after, Princeton scientists announced they’d made a fluorescent bacterium that could flash on and off.
The idea was to program cells to carry out all kinds of new and useful functions. It proved irresistible — there have been countless experts panels, a TED Talk, and an international student competition.
But Synlogic’s plan for a GM pill is one of the first concrete medical applications of such ideas. It involves deleting and adding several genes to a harmless strain of E coli, the gut bacterium, so that it develops an unquenchable appetite for ammonia, formed from the nitrogen we get from eating protein.
Normally, extra nitrogen is turned into urea and we just pee it away. But some people can’t process it fast enough.
They end up instead with ammonia levels that can be toxic enough to kill newborns and in kids and adults can cause delirium and angry behaviour. Synlogic’s E coli would take ammonia and turn it into arginine, a harmless amino acid.
A person would probably swallow a capsule once a day containing about 100 billion bacteria, says JC Gutierrez, the company’s CEO. The company has so far raised $70-million from venture capitalists.
It’s not just rare diseases being targeted with redesigned bacteria. Startups like Ernest Pharmaceuticals, recently formed by University of Massachusetts professor, Neil Forbes, plan to fight cancer using salmonella, a bacterium best known for causing food poisoning that also has a habit of congregating in tumours.
Forbes thinks the germs can be programmed to recognise they’re in a tumour and release anti-cancer drugs too toxic to be given as an injection.
Previously, one European company, ActoGenix, tested pills containing GM bacteria, but no GM germ pill has yet gone on sale, and the idea remains novel enough that there’s no agreement on what to call such medicines. The US FDA has designated them as “living biotherapeutic products”.
Currently, as many as eight to ten GM bugs are awaiting a green light from the FDA for early testing in the US, estimates Yamil Hernandez, cofounder of Thayer Pharmaceuticals, a startup in Maryland that intends to engineer a yoghurt bacteria, lactobacillus, to consume phenylalanine, an ingredient in milk, nuts, and in the aspartame used in diet sodas that some people can’t digest.
Hernandez says a germ designed to metabolise it could be sprinkled as a powder on food. “It’s like hungry, hungry hippo, just with a very strong preference for phenylalanine,” he says.
Using bacteria as a treatment isn’t new to medicine. The vaccine against tuberculosis is made with weakened germs. And the US probiotics market is worth $3.5-billion……