There
are probably at least 500 medically useful chemicals awaiting discovery
in plant species whose chemical constituents have not yet been
evaluated for their potential to cure or treat disease, according to a
new analysis by a New York Botanical Garden scientist who has more than
15 years of experience in collecting plants for natural-products
discovery programs.
Currently,
135 drugs on the market are derived directly from plants; the analysis
indicates that at least three times as many disease-fighting substances
have yet to be found that could be developed into drugs or used as the
basis for further drug research.
“Clearly,
plant diversity has not been exhausted, and there is still great
potential in the plant world,” said James S. Miller, Ph.D., Dean and
Vice President for Science at the Botanical Garden.
Miller’s analysis, “The Discovery of Medicines from Plants: A Current
Biological Perspective,” is published in the December issue of the
peer-reviewed journal Economic Botany.
To
arrive at his estimate, Miller used a formula based on the ratio of
the number of drugs that have been developed from plants to the number
of plants that were screened to find those drugs. He then applied that
ratio to the number of plant species that have not yet been screened.
Because
of uncertainties in some of those numbers, the formula yields a range
of potential drug discoveries. While there is no general agreement among
botanists about the number of plant species that are likely to exist, Miller concluded that there are 300,000 to 350,000 species of
plants. Of those, he determined that the chemistry of only 2,000 species
has been thoroughly studied, and perhaps only 60,000 species have been
evaluated even partially for medicinally useful chemicals.
Working
with those numbers, Miller calculated that there are likely to be a
minimum of 540 to 653 new drugs waiting to be discovered from plants;
the actual number could be much greater.
“These
calculations indicate that there is significant value in continuing to
screen plants for the discovery of novel bioactive medicinally useful
compounds,” concludes Miller, who has run natural-products discovery
programs that have collected specimens in North America, Central and
Southeast Asia, and Africa for government agencies, pharmaceutical
companies, and academic programs.
As
part of his Economic Botany paper, Miller reviews the disappointing
history of past plant-screening efforts and evaluates the potential for
future programs.
Technological
advances in the 1970s and 1980s gave medical researchers the capacity
to evaluate large numbers of plant samples. That prompted the federal
government and large pharmaceutical companies to institute aggressive
plant collecting and screening programs. Those programs led to the
development of several important drugs such as Taxol from Taxus
brevifolia (used in cancer treatment) and Camptothecin from Camptotheca
acuminata (derivatives of which are used to treat cancer). Other drugs
indirectly trace their discovery to natural-products research, including
the anti-viral Oseltamivir, which derives from Illicium anisatum and is
marketed in the United States as Tamiflu.
The
number of drug discoveries, however, was substantially less than
anticipated. By the early 2000s, many of the large pharmaceutical
companies had abandoned their efforts.
Miller argues that one possible explanation for the low yield is the
relatively crude way in which plant extracts were tested for their
pharmaceutical potential. Plants may contain as many as 500 to 800
different chemical compounds, but the screening programs of the late
20th century used extracts made from a whole plant or at best extracts
that contained many hundreds of compounds.
Under
those circumstances, one compound may interfere with the action of
another, or the amount of one compound may be too small to register in a
mix of hundreds of chemicals.
To
correct this problem, new technologies now allow researchers to
separate complex mixtures of natural products into a “library” of
relatively pure compounds that can be tested individually. A 2002 study
demonstrated that testing such libraries dramatically improves discovery
rates.
Bringing
these advances together with refinements in collecting strategies could
lead to what Miller calls a “second renaissance” of
natural-products discovery.
Miller
undertook his analysis to highlight the fact that despite past
collecting programs, the plant world represents a poorly explored source
of potentially lifesaving drugs. That adds urgency, he said, to efforts
to conserve natural habitats so that species are not driven to
extinction before they can be studied.
“The
natural world has a great and diverse array of interesting chemicals
that have been only minimally studied and still hold considerable
potential,” he writes.
The Discovery of Medicines from Plants: A Current Biological Perspective
