As antibiotic resistance increases, audacious expeditions are taking the quest for new medicines to the ocean depths, and not a moment too soon
THE 150-kilometre trip out from Chile won't be comfortable. It will be hot, choppy and take all night. Travelling across this patch of the Pacific Ocean, you run afoul of both El Niño and La Niña, whose perpetual tug of war with the weather can make even the most stoic seafarers lose their lunch.
Luckily, once the crew – an eclectic mix of hardened South American mariners and British salvage engineers – reach their destination, they should find placid waters. That will make it a lot easier for the engines to steady the ship's position. They certainly can't use an anchor: out here, the ocean floor is 8 kilometres down, a treacherous abyss known as the Peru-Chile trench. But what the team haul out of these depths could save your life.
The Peru-Chile trench is only the first stop. This year, Marcel Jaspars, a chemist at the University of Aberdeen in the UK, is leading an international raid on the unexplored recesses of the oceans. The exotic organisms that thrive there could be pressed into service against some of our worst enemies, from cancer to drug-resistant bacteria. There's not much time to lose. Without them, some say we may be heading for an antibiotics apocalypse.
We have always relied on nature to fill our medicine cabinets. Over half of all drugs on the market are either derived from or inspired by plants, animals or bacteria – aspirin is extracted from the bark of the willow tree, penicillin comes from a fungus, and we have soil bacteria to thank for many antibiotics.
Some of these discoveries were happy accidents, but traditionally pharmaceutical companies went foraging for medicinal treasures in remote locations – a practice known as bioprospecting. Such expeditions have struck gold in the past: vinblastine, a chemotherapy drug used to treat Hodgkin's lymphoma, is derived from the rosy periwinkle, a plant native to Madagascar.
Out of time
But over the past 20 years, conventional bioprospecting has seen diminishing returns, particularly among microorganisms. The same thing keeps happening; bioprospectors find a promising candidate, companies spend small fortunes on development – only to find that everyone has wasted their time. This is happening even as our need for new antibiotics grows steadily more urgent, says Laura Piddock, a microbiologist at the University of Birmingham, UK, who directs a global initiative to develop new antibiotics.
Antibiotic-resistant strains of gonorrhea, tuberculosis and MRSA are on the rise. Such bacteria have evolved resistance mechanisms even against the antibiotics of last resort. Within a decade or two, they will have become resistant to all major antibiotics, and simple infections will become fatal. But no new organisms have been found on which to base better drugs. "The pipeline is pretty empty," Piddock says (see diagram).
Desperate for new compounds, pharmaceutical firms turned to synthetic analogues. But these have not equalled the natural diversity that has evolved over billions of years. The effect has been fewer products, not more, says Guy Carter, an industry consultant in New York.
But Jaspars is convinced nature still has a few tricks up her sleeve. The organisms that flourish in the comfort zone of Earth's biosphere make up only a fraction of life on our planet. Outside what we consider the habitable regions – in the desiccated soils of deserts or buried beneath thick ice or rock – creatures not only survive, but thrive, at extremes of temperature, salinity and darkness.
We first realised that their unusual adaptive chemistry could be used to our advantage about 40 years ago. Thomas Brock – at the time a microbiologist at the University of Washington – was driving through Yellowstone National Park on his way back to the lab. The hot pools and geysers proved too tempting; he stopped to admire them and returned to the lab with a water sample. He was stunned to discover life thriving in the near-boiling liquid. So began a decade of study of thermally resistant microbes. One species, Thermus aquaticus, turned out to make an enzyme, taq polymerase, that was key to automating methods used to amplify small amounts of DNA. It turned a tricky, labour-intensive process into one doable on any lab bench, effectively ushering in the genomics revolution.
It wasn't until a few years ago that we began to realise that these adaptations could also be turned against some of our nastiest medical foes. Fungi discovered in the acidic lakes of Lechuguilla Cave in Carlsbad, California – whose metal-infused waters should have stymied all life – tipped us off (see diagram). One hardy strain of Penicillium produces a compound that inhibits the growth of lung cancer cells. Another compound, berkelic acid, isolated from fungus and bacteria found living in the toxic water of an open pit mine, slowed ovarian cancer cell growth by 50 per cent (Journal of Organic Chemistry, vol 71, p 5357). The hunt was on to unearth more of nature's extreme medicines.
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