The Importance of Biodiversity to Medicine

In the past 12 months alone, more than 1000 new species were identified.¹ Some were found in Earth's most remote locations, such as the Weddell Sea off Antarctica or central Australia's Simpson Desert, where 3 species of carnivorous sponges and a new microbat species were found, respectively. In addition, nearly 100 previously unknown species of bacteria were found to be inhabiting human epidermis. When it comes to biodiversity—a term that describes the variety of life on the planet—the more scientists look, the more they find. But these discoveries represent far more than just novelty. In them can be found a major engine of advancement for medicine and biomedical research and a new lens with which to look on human health and disease.

A Canadian scientific expedition to Easter Island in 1964 provides an example of how biodiversity can benefit medicine. In a remarkable stroke of luck, the scientists brought home a scoop of soil containing Streptomyces hygroscopicus, the bacterial source of sirolimus, a drug that has revolutionized the treatment of solid organ transplant rejection.² Sirolimus and its derivatives have also shown promise in the treatment of brain, lung, endometrial, and kidney tumors and as a coating for arterial stents to prevent restenosis. Serendipity of this sort has arisen not only in exotic places but also in familiar ones. For example, Chromobacterium violaceum was cultured from the Pine Barrens of New Jersey, leading to the discovery of aztreonam, a principal antibiotic used in the treatment of gram-negative infections.

Science has routinely appropriated microbial compounds for human use, ranging from old stalwarts such as penicillin, aminoglycosides, and tetracyclines to the new lipopeptides (eg, daptomycin) and antifungals (eg, caspofungin). But the reliance on natural products in drug development extends far beyond antimicrobial applications. Studies involving snakes, sea squirts, sponges, and snails have led to the discovery of angiotensin-converting enzyme inhibitors, trabectedin (a new treatment for soft tissue sarcomas), the antivirals azidothymidine and acyclovir, and ziconotide, respectively. Despite enormous investment into synthetic drug development, about half of the 100 most prescribed medications in the United States and about half of the new drugs approved by the Food and Drug Administration in the past 25 years derive directly or indirectly from nature³ (Table).

Natural products compose a superb resource for drug discovery because they have evolved, in some cases during millions of years, to exploit fundamental biological pathways often shared by humans. In addition, the random aspect of the evolutionary process gives rise to products with unforeseen, and perhaps unforeseeable, biological actions, allowing for the development of pharmaceuticals with novel mechanisms of action. For example, paclitaxel (discovered in the bark of the Pacific yew tree), a mainstay of chemotherapy for a variety of cancers, was the first drug shown to inhibit microtubule breakdown during mitosis.⁴

The ability of nature to devise novel approaches to biological challenges has proven especially valuable to biomedical research. To survive in the extremely hot water of Yellowstone Park's Mushroom Spring, the bacterium Thermus aquaticus has enzymes that remain functional at high temperature. One of its heat-stable enzymes, DNA polymerase, was instrumental in the development of the polymerase chain reaction, for which the Nobel Prize was awarded in 1993. Another Nobel Prize was awarded in 2006 for a discovery involving a common flower. Intending to produce more intensely colored petals, researchers introduced extra copies of a pigment gene into petunias. The resulting flowers were, against expectation, partially or totally white. The molecular basis for this effect was found to be RNA interference, a fundamental biological mechanism for inhibiting gene expression that has great potential to treat neurodegenerative disease, cancer, infection, and other medical conditions.⁵

A number of scientific breakthroughs have come from studies involving some of the 100 000 or more venomous peptides produced by sea snails of the genus Conus.⁶ These slow-moving predators, which live on or near coral reefs (among the most endangered habitats on earth), subdue fish with a precise chemical assault directed at their prey's nervous system, leading to rapid paralysis. Peptides isolated from Conus species bind many molecular targets, including ion channels (sodium, potassium, and calcium) and cell membrane receptors (N-methyl-D-aspartate, adrenergic, and cholinergic). Because of their diversity and specificity, these peptides have significantly advanced research into biological pathways, particularly in neuroscience. For instance, the analgesic ziconotide, based on a peptide derived from the sea snail Conus magus, is used to treat neuropathic pain through a novel mechanism: calcium-channel blockade in the dorsal horn of the spinal cord. Although this drug is 1000-fold more potent than morphine, ziconotide does not appear to elicit tolerance.⁷

Many new species are yet to be found in the earth's soil, deep oceans, polar regions, and other habitats. For this reason, ecosystem disruption can be expected to impede progress in medicine and biomedical research through the loss of countless unidentified species. But disruption of ecosystems can affect human health in other ways, as exemplified by Lyme disease, the most common vector-borne illness in the United States. Many vertebrate species serve as reservoirs for Lyme, although not all transmit disease-causing spirochetes to the black-legged tick, the principal vector, with equal competence. In North America, the most competent reservoir is the white-footed mouse, and this rodent tends to outcompete other reservoir species in fragmented, new-growth forests. Consequently, the black-legged tick, an indiscriminant parasite, is more likely to become infected when it feeds in disrupted forests such as those of New England, where Lyme is endemic, than in undisturbed areas.⁸ This particular phenomenon, in which vertebrate reservoir diversity buffers against disease transmission (termed the “dilution effect”), may also occur with West Nile virus and hantavirus. Of the 1415 infectious agents known to cause disease in humans, more than 60% have life cycles that involve other species,⁹ and disruption of their habitats may affect public health in various, unexpected, and potentially devastating ways.

Another mechanism by which habitat disruption may cause disease is through changes in human behavior. A 2004 report¹⁰ indicated that depletion of fish stocks off the coast of western equatorial Africa, because of industrial fishing practices driven by the increasing worldwide demand for seafood, had forced many in the affected areas to abandon traditional subsistence fishing practices and instead resort to eating bush meat. The following year, 2 new retroviruses, human T-lymphotropic virus 3 and 4, were detected in the blood of local inhabitants who, in a manner reminiscent of the initial transmission of human immunodeficiency virus into humans, likely acquired the infections by consuming nonhuman primates infected with nearly identical viruses.¹¹ In view of the vast effect human civilization has had on the earth's land surface, freshwater bodies, and oceans, it may come as no surprise that 60% of emerging infectious diseases during the past 60 years are zoonotic.¹²

The diversity of life in and on the human body also has considerable relevance to health. Current estimates suggest that the number of microbial species is about 180 on the skin, 700 in the mouth, and 1000 or more in the gastrointestinal tract. ¹³ Alterations in the ecology of the gastrointestinal tract, in particular, may be related to incidence and severity of food allergy, asthma, eczema, inflammatory bowel disease, and obesity. For this reason, interest in probiotics has increased, and data suggest that the use of gut bacteria (eg, Lactobacillus acidophilus) is safe and in some situations may be helpful. But just as the reintroduction of one or a few species into a severely disrupted terrestrial habitat will not likely restore ecological balance, so also may probiotic treatment have limited effectiveness without comprehensive changes in diet.

The current rate of species extinctions is estimated to be 100- to 1000-fold faster than would occur in the absence of humans on the planet.¹⁴ The main reason for present-day extinctions is habitat loss caused by myriad human activities. By midcentury, climate change is predicted to surpass habitat loss as the leading cause of species extinctions.

Physicians have a unique responsibility for, and ability to help prevent, loss of biodiversity. According to the Department of Energy, health care is the second most energy-intensive industry in the United States, generating an exceedingly high rate of greenhouse gas emissions per square foot. Hospitals and health care offices also produce enormous amounts of waste, estimated at 6600 tons a day,¹⁵ much of which is toxic or nonbiodegradable owing to a heavy reliance on single-use, plastic-based products. Thus, energy conservation and improved waste management in the health care industry have great potential to reduce 2 leading causes of biodiversity loss. In addition, health care professionals aware of the importance of biodiversity to the practice of medicine can be especially powerful advocates to patients and the government for comprehensive action throughout society to protect the environment on which all species, including humans, depend.