Evolutionary trees of traditional medicine plants provide hints for drug-makers

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There’s a bizarre mindset that divides medicine into “natural” (made from plants; untainted by villainous pharmaceutical companies; delivered to your veins by forest animals) and everything else (“man-made” pills fashioned from profits and poisons). The reality, of course, is that many of the drugs used in our hospitals and pharmacies come from plants. Willow bark contains salicylic acid, the main ingredient in aspirin. Paclitaxel (taxol) was isolated from the bark of the Pacific yew tree; today, it is used to stop cancer cells from dividing.  The rose periwinkle has given us vinblastine and vincristine, both used to treat leukaemia.

These examples scratch the surface of what the botanical world has given us, and what it might still offer. Of the tens of thousands of plants used in “traditional medicine”, a piddling proportion has been tested for chemicals with medical benefits. How do we find the rest? How do we go about the business of “bioprospecting”? One solution is to tap the knowledge of indigenous populations, who still rely on plants for traditional medicine. When they get sick, how do they heal themselves?

But this approach has problems. Traditional use doesn’t always imply an actual medical benefit, and the chosen plants might not yield interesting chemicals any more readily than the species around them. Many attempts to follow such leads have ended in the drug-development cul-de-sac. To make matters worse, collating traditional knowledge involves fieldwork and training, and is both expensive and time-consuming.

Meanwhile, the tools of molecular biology have become faster and cheaper. Companies can afford to gather large collections of plants, and screen their constituent chemicals en masse. Why filter them any further when you can test thousands of samples at once? But Haris Saslis-Lagoudakis from Imperial College London thinks that this scattershot approach to bioprospecting is a mistake. To him, traditional knowledge still has great value in honing our search for tomorrow’s drugs.

He made his point by creating a family tree (a phylogeny) of over 20,000 plant species from New Zealand, Nepal, and the Cape of South Africa. Around 1,500 of these are used in traditional medicine and these, rather than being spread out throughout the family tree, are actually clustered in certain branches. The “hottest” branches contained 60 per cent more traditionally used plants that you’d expect if they were distributed randomly.

As one example among many, rushfoil (Croton) and physic nut (Jatropha) are close relatives form the spurge family, and are both used to treat malaria in Nepal. “We know that close relatives can share many of the chemical compounds they produce,” says Saslis-Lagoudakis, “so our results suggest that the use of Croton and Jatropha to treat malaria is due to underlying shared chemistry between them.”

Saslis-Lagoudakis also found that people tend to use related plants from the three continents to treat medical conditions that afflict the same organs. For example, members from the soapberry family (Sapindaceae) are used to treat digestive problems in New Zealand (Alectryon), Nepal (heartseed and Ceylon oak) and South Africa (jacket plum). Since these places are so distant, and their native floras are so radically different, it’s likely the people there discovered the properties of their local plants independently.

To Saslis-Lagoudakis, these trends suggest that plants don’t make their way into a healer’s repertoire through superstition or chance. Instead, it’s their medical properties – their bioactivity – that makes them useful. And since drug manufacturers search for those same properties, the evolutionary relationships between traditionally used plants could help to guide their search.

But Michael Heinrich from University College London cautions that there could be other explanations for the results. Saslis-Lagoudakis thinks that the close relationships between traditionally used plants reflect their chemistry. Heinrich wonders if it reflects their “weediness”. Weeds are more likely to be found and used, and families that are rich in weeds – such as daisies and mints – are a common part of traditional repertoires. “If you have to search for something to treat your diarrhoea, would you walk up to the Welsh mountains and try to get a rare endemic species or just use what grows in your backyards?” says Heinrich.

Still, it seems that bioprospectors are already on the path of using traditional knowledge, even if they’re not aware of it. When Saslis-Lagoudakis listed all the plants that have yielded chemicals either already in use, or going through trials, he found that they’re more likely to belong to groups being used in traditional medicine, and to the “hot” branches of his family tree.

Within these branches, question marks hang over more than 80 percent of species. They haven’t been checked by bioprospecting companies, and many aren’t being used by traditional healers. We have no idea what chemicals they contain, and Saslis-Lagoudakis writes that they “have high potential to deliver new medicines”.

He thinks that even in the era of cheap powerful molecular biology, traditional knowledge can make bioprospecting programmes more effective in three ways. They can tell us which conditions plants are used to treat, which could help to focus our tests. They can reveal which parts are used, and which organs can be ignored.  And they can show how the plants are processed before being used, which “indicates how best to prepare a plant sample for testing.”

“We hope our new methods in how traditional knowledge can be used to search for new drugs will direct bioprospectors back towards traditional medicine, and encourage more ethnobotanical fieldwork,” he says.

Heinrich agrees with the need for more fieldwork, especially in “the many understudied regions of the world, such as Southern Africa, New Zealand, and South and Central America”. But he cautions that bioprospecting companies also take other considerations into account, like how different new compounds will be to existing ones, and how more effective they will be to existing gold standards. It’s not just about the chemistry; it’s about the applications too.

Reference: Saslis-Lagoudakis, Savolainen, Williamson, Forest, Wagstaff, Baral, Watson, Pendry and Hawkins. 2012. Phylogenies reveal predictive power of traditional medicine in bioprospecting. PNAS http://dx.doi.org/10.1073/pnas.1202242109

Photos by Stan Shebs (left) and Neelix (right)