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Drugs rotting on the vine

With Ebola threatening the world's populations, there is a new urgency to find therapies. Bringing naturally occurring pharmaceuticals to market should be a priority for our nation because drugs derived from nature are astonishingly successful. The United States' policy and law, however, strongly discourage prospecting for drugs in nature.

This spring, the United States Patent and Trademark Office ruled that natural products cannot be patented. The United States also refuses to be bound by a United Nations treaty that came into effect earlier this month, intended to facilitate discovery of natural products in biodiverse places like the Amazon rain forests. Currently, there is limited drug exploration in the natural world because previous treaties have failed fully to clarify who can explore and who gets to profit. This vagueness scares away investors. The United Nations treaty — Nagoya Protocol to the Convention on Biological Diversity — for the first time establishes clear rules on how profits derived from natural products are to be shared with people who live where the products are discovered. The United States must reverse course and start to incentivize the search for drugs in nature. We must ratify the UN treaty and change our patent law.

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Compounds derived from nature account for 70 percent of all anti-tumor and anti-infective drugs that have come to market in the last 30 years. This is amazing in light of drug companies' lack of investment in natural compounds. For the last approximately 20 years they have favored drugs they have designed and built from scratch because long before the patent office's tragic ruling this spring, it was difficult to protect intellectual property rights for natural drugs. How then can there be so many natural drugs on the market if companies have not pursued them aggressively? Even though they are less profitable, natural drugs are far easier to find and are often more effective than the drugs synthesized from scratch.

The current system rewards companies for the inefficient work of inventing entirely new molecules and hardly at all for the more efficient exploration in nature. It is as if we rewarded our police officers primarily for handling minor traffic violations and not much for their more valuable task of catching dangerous criminals. If the drug companies were given incentives to pursue natural products, it follows that we would have many more therapies and more effective ones.

One important advantage of therapies from the natural world comes from nature's heroic investment in research and development. Millions of species on this planet have spent millions of years developing chemical therapies using trial-and-error science — that is, evolution — to address many of the health issues for which we humans take medicine. Non-human species also get cancer, infections and diseases of inflammation. So they have developed their own chemotherapies, antibiotics, antivirals and anti-inflammatory drugs. Millions of years, millions of species, trillions of hours. That's a commitment to innovation.

Compare that to research and development investment by pharmaceutical companies. An executive at America's leading consulting firm that specializes in corporate layoffs sent me data showing that pharmaceutical companies have been laying off many thousands of researchers each year for over a decade, with 2014 so far being no different. David Newman, chief of the Natural Products Branch at the National Institutes of Health, explained to me that at times, drug company scientists do much of their initial drug discovery by calling scientists at universities and in the government and asking for information on novel structures that may be basic blueprints for drugs, often as a favor.

Another advantage of naturally-derived drugs is their three-dimensional form. Pharmacological compounds produced by organisms often have many contours and often fit neatly together with the highly individualized molecules in human bodies, which are also three-dimensional. Yet pharmaceutical laboratories are generally limited by existing technology to synthesize flat molecules. Flat puzzle pieces for three-dimensional puzzles are hard to find, and they usually don't work very well.

Even when initial tests on bacteria and fungi show no evidence of useful compounds, scientists are now learning how to turn on hidden, unexpressed genes that produce potential therapies. This would be great news for the future of health care, if it were not for misguided laws and policies that make it difficult for companies to invest in such therapies.

S. Morgan Campbell is a second-year medical student at The University of Wisconsin School of Medicine and Public Health. His email is scampbell4@wisc.edu.

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