Discovery Could Save Whales, Lead to Better Drugs

April 12, 2012 — -- Here's something you really need to know: Some of the most expensive perfumes include a compound extracted from whale vomit. No kidding.

However, new research from the University of British Columbia may eliminate the need to use waste products from an endangered species to make humans smell better. And therein lies a tale of the sometimes-twisted road to better and cheaper drugs, cosmetics, booze and biofuels.

Nature does it best. But replicating the fine work of weeds and trees from whence many drugs come has often proved difficult. In the case of whale vomit, some consumers find the idea of using regurgitated squids and ocean slime, no matter how good it might smell, a bit repulsive.

And it poses such a threat to whales, because of the possibility of poaching, that many countries, including the United States, banned the use of sperm whale vomit in the 1970s.

But since 2005, the practice became legal again in the U.S., but only because the substance can be collected along the coastline through carefully monitored programs.

Still, it's not easy to identify whale excreta among the muck that covers many beaches, and harvesting is so labor intensive that a single gram can cost up to $50.The stuff is literally collected by hand by workers up and down both the Atlantic and Pacific coasts and the Caribbean who have been trained to recognize it's rock-like appearance. But some environmentalists are still concerned the value of the material is likely to encourage poachers to kill whales and remove it directly from their intestinal tracts.

That led Joerg Bohlmann, professor of Botany and Forest Sciences at the University of British Columbia, to look for a substitute.

Bohlmann and his postdoctoral research associate Philipp Zerbe found what they were looking for in balsam fir trees. They isolated the gene that produces a compound in the fir trees that is remarkably similar to ambergris, the ingredient in whale excrement and vomit that is so desirable in the perfume industry.

Ambergris makes the perfume adhere to the skin better, thus prolonging its life, and it also binds the other compounds that produce the desired odor.

So how do you get from a fir tree to whale vomit? Simple, Bohlmann said in a telephone interview. You take the gene he isolated in the tree, put it in a clump of yeast, and the yeast becomes a biological factory, churning out the substitute for ambergris like, well, a factory.

Yeast, a unicellular fungi found all over the world, especially on leaves and flowers, has been a workhorse in many laboratories for decades. Genetically, yeast is very simple; yet it shares many aspects of cellular development with more complex organisms, including mammals.

"Using yeast as a microorganism for producing interesting products for human needs goes back a very, very long time," Bohlmann said. In the past, that included products ranging from biofuels to wine, normally in fermentation vats. But quite recently, scientists have taken a closer look at their old friend.

"It is a very simple organism and it can easily be genetically modified by putting in a particular gene and you can train it to produce compounds," Bohlmann said.

Just plug in a gene and the yeast becomes a biochemistry factory?

"It's that simple," he said, though fine tuning the process can be very complex and take years.

While Bohlmann's work hasn't progressed quite that far yet, he's past the "proof of concept" phase and has joined with other researchers who expect to move on to the production level.

But this story isn't just about whale barf. If the concept works there, it should have other applications. Many useful compounds begin with nature, including many pharmaceuticals, but it isn't always possible to rely on samples collected from trees, plants and other animals to satisfy the huge demands for modern drugs and other consumer products.

So scientists try to produce synthetic substitutes for useful compounds found in nature, and that process will continue on a large scale. That's essential, but it isn't always possible.

One interesting case involves taxol, a natural compound discovered in 1967 in yew trees, conifers found across much of North America. A short time later it was discovered that taxol might be useful in the fight against cancer, but it soon became clear that it would take a lot of trees.

In 1988, just as taxol was entering the second phase of clinical trials, the National Cancer Institute came up with an astounding figure. About 360,000 yew trees would be destroyed annually just to get the drug through the trials.

"There's not enough yew trees to supply all the taxol that is needed," said Bohlmann, whose research was published in the current issue of the Journal of Biological Chemistry.

Fortunately, researchers found the precursor that produces taxol in yew trees that grow as hedges, greatly reducing the demand on the plants. It also opened a new frontier.

Chemists were able to modify the precursor to produce synthetic substitutes that yielded "the best of both worlds," Bohlmann said. "You get the best of the natural product, and you get the refinement that comes from chemical synthesis in the laboratory."

Thus the yews were saved from destruction, and industry was able to produce sufficient quantities of a drug that has saved thousands of lives. Yet within the last five years or so, according to Bohlmann, scientists have turned increasingly to microorganisms – like yeast, which is now used as one way to produce taxol – as production platforms for natural products.

His works suggests that simply isolating a single gene – as he has done with the balsam fir tree – and placing that in a vat of yeast, may become a major player in the effort to extract the best from nature in a benign way and produce highly useful compounds.

That would be very nice for yew trees.