| Features | Spring 2009 |
|
Design for Life It’s often the ugly and the small that sustain life. Consider, for example, the gastric brooding frog. Native to Australia, both the northern and southern branches of this frog species are small—about the length of a jumbo paperclip—and with large protruding eyes, flattened heads, slimy skins, and dull or dun colorations, not quite candidates for poster amphibian. And then there’s its name, painfully practical: A female gastric brooding frog swallows fertilized eggs and hatches them in her stomach. It’s a curious process but, from a medical standpoint, a fascinating one. After the eggs develop into tadpoles—and before the mother frog spews them forth to develop into adults in the outside world—the brooding tadpoles apparently secrete a substance or substances that inhibit the mother frog’s digestive process, thus turning an inhospitable environment hospitable. Those substances intrigue medical researchers. Could they help prevent, perhaps even treat, peptic ulcer disease, a condition that affects more than 4 million people in the United States alone? The question is a tantalizing one. And one never to be answered, for the gastric brooding frog, abundant in the early 1970s, disappeared several years later. For more than a decade now, it has officially been listed as extinct. The reasons for this disappearance could be several: climate change, destruction of the frogs’ forest and stream habitats, infection by a lethal fungus. But the results are clear. A small creature is gone because of human activity, the diversity of species inhabiting our planet has been lessened, and knowledge that could have helped doctors alleviate suffering has vanished for all time. About a decade ago, I became part of a scientific effort to investigate the potential consequences to human health from the loss of species such as the gastric brooding frog. Together with colleagues from Harvard Medical School’s Center for Health and the Global Environment, the International Union for Conservation of Nature (IUCN), and three agencies of the United Nations—the Environment Programme, the Development Programme, and the Secretariat of the Convention on Biological Diversity—we gathered and sifted data on the well-being of humans and our planet. We found the two to be inextricably entwined. Our findings underscored the need to preserve the planet’s biodiversity—its ecosystems, species, populations, and gene pools—if we are to preserve human health. Recycling Center Although the gastric brooding frog can no longer benefit from improvements we make as active stewards of this planet, other animals can. The polar bear is one such animal. This magnificent mammal is one of nine bear species threatened with extinction, according to the IUCN. The threats come from habitat destruction, overhunting, and, for the polar bear in particular, exposure to persistent organic pollutants and climate change. Increasing temperatures are thinning the Arctic ice, a condition that compromises the bears’ ability to hunt seals, their primary food source. In fact, during the bears’ peak hunting season, seals are the first, and often only, item on the menu. Dining on seal blubber allows a polar bear to build a layer of fat several inches thick directly beneath its skin. Just when this steady diet of seal blubber leads to a state of obesity, the bears begin a several-month period of fasting. Given their obesity, we would expect polar bears to develop type 2 diabetes mellitus, and, in fact, their cells do show some insulin resistance. Yet polar bears do not develop the disease. Instead, their metabolism of glucose and fat and their production of insulin adjust to meet their changed circumstances. Insight into how polar bears accomplish these metabolic feats could well inform how we treat, and maybe even prevent, type 2 diabetes, a disorder that has reached epidemic proportions in the United States. The promise that understanding polar bear physiology holds for humans with diabetes expands when we examine the physiologies of other bear groups. Research conducted during the past quarter century on hibernating black bears, for example, has shown that during their three-to-six-month period of inactivity they do not lose bone mass, nor do they urinate or defecate. By contrast, humans who are bedridden for five months lose one-quarter to one-third of their bone mass. More dramatically, an inability to excrete urinary wastes for several days poisons and eventually kills a person. How is it that bears survive similar circumstances unharmed? They recycle. Calcium released by the bones cycles back into bone. Urine is reabsorbed by the bladder and returned to the bloodstream; the reabsorbed urea is used as a building block to form new amino acids, which assemble into new proteins; and free fatty acids are returned to fatty tissue, not broken down to release ketone bodies as their end product. The overall result of this remarkable internal chemistry is that, during hibernation, bears lose body fat, increase lean body mass, and maintain bone integrity and healthy renal function. To add to that remarkable litany, females that are pregnant when they start their period of fasting and hibernation give birth and provide nutritious, high-fat milk to growing offspring. Even if our study of hibernating bears led only to an effective treatment for osteoporosis, a disease that currently afflicts about 10 million people in the United States alone, protection of these animals would be worthwhile. But research on bears also has shown us that their metabolic accomplishments could inform our treatment of such medical conditions as obesity, diabetes, chronic malnutrition, anorexia nervosa, and atherosclerosis. Shell Gains It’s not simply the promise of medical advances that may be found in nature. Cone snails—marine mollusks that live in the soft bottoms of mangroves and in coral reefs—have delivered on the promise. Each of the world’s estimated 500 to 700 cone snail species is believed to produce between 100 and 200 distinct peptide toxins. The snails defend themselves and paralyze their prey—other mollusks, worms, and fish—with these toxins, delivering the poisons through a hollow, harpoon-like tooth. The total number of toxins produced by this one genus of snails is remarkable—50,000 to 140,000, compared with only about 10,000 alkaloids that have been identified in all known plants. Pit vipers and other poisonous animals taken together produce only a handful of different poisons. But cone-snail toxins, known as conotoxins, also are exceptional in that each binds with such potency and extreme selectivity to one of an enormous array of receptor sites. This discriminating ability has made conotoxins a must-have for biomedical research and a rich resource for the development of new medicines. Conotoxins have, for example, helped scientists characterize certain of the subtypes of nicotinic acetylcholine receptors found in skeletal muscle, in the brain, and in mammalian heart muscles, where they have contributed to our understanding of the mechanisms that control heart rate and contractility. Other conotoxins have allowed researchers to identify calcium, potassium, and sodium ion channel subtypes, advancing our knowledge of the toxins’ fundamental molecular units. These toxins may also prove useful in diagnosing early cases of some elusive and stubborn cancers, like small-cell carcinomas of the lung, as they can help identify circulating antibodies formed in response to certain cancers, such as those that cause the autoimmune neurological disease Lambert–Eaton myasthenic syndrome. These contributions may seem considerable, but they likely represent a mere fraction of the biomedical treasures cone snails may offer. To date, less than 1 percent of conotoxins have been defined and only a small subset of this group has been analyzed for biological activity. From these few efforts, however, several potential new medicines have been identified. One, a painkiller called ziconotide, has been shown to be a thousand times more potent than morphine. Unlike morphine and other opiates, however, ziconotide leads neither to tolerance nor addiction. In 2004, the U.S. Food and Drug Administration approved the use of this compound for the management of severe chronic pain in patients who no longer respond to opiates. Another toxin that blocks a type of neurotransmitter receptor called the NMDA receptor has been shown to protect neurons from cell death in situations in which circulation is inadequate, such as during strokes and head injuries. Other conotoxins that block NMDA receptors could open the way to new antiepileptic treatments. The potential pharmacopoeia that cone snails offer humans understandably makes the snails sought-after items for biomedical research. But such popularity comes at a cost. Harvesting the snails for biomedical research, a practice that tends to be carefully controlled, may simply be contributing a new twist to the overhunting these snails have long suffered at the hands of another set of collectors, those captivated by the beauty and variety of the snails’ shell patterns. The snails’ habitats also face environmental insults. An estimated 20 percent of the world’s coral reefs are so damaged they are unlikely to recover; another 50 percent are at risk of collapse. Carbon dioxide, released into the atmosphere during the burning of fossil fuels, threatens reefs in two ways: by dissolving in seawater, thereby increasing its acidity and inhibiting the calcification of the corals that make up the reefs, and by causing sea surface warming, which affects the viability of algae that provide the corals with nutrients. Mangroves too are being threatened, uprooted for wood, development, and aquaculture and devastated by natural catastrophes such as tsunamis. An awareness of these threats—and a willingness to act to stem them—can help conserve this population; countries like Australia have recently established restrictions on the collection and trade of cone snails. Yet many countries in Southeast Asia, where more than half the world’s cone snail species are found, have no such controls. You Can’t Bottle Sunshine It may seem odd to link the existence of a tiny frog that once lived on a single continent, a bear that forages in the frigid far north, and a snail that inhabits reefs and mangroves found only in tropical seas to that of humans populating the far reaches of the world. But such links are real. With the loss of animal, plant, and microbial species, we lose not only new medicines and vital models for medical research, but also the contributions those species make to ecosystems. Such losses disrupt the interdependent webs of life that pollinate crops, convert wastes and dead organisms into nutrients for the soils and oceans, hold infectious diseases in check, and perform a host of other essential services that spark and sustain the lives of all organisms on Earth. Our failure to recognize the link between our health and that of the planet’s species and ecosystems is at the core of the global environmental crisis. We delude ourselves—dangerously so—if we think that taking action to preserve the natural world is simply a matter of choice. It is not a choice; it is a necessity. Our health and our lives depend on it. Eric Chivian ’68 is founder and director of the Center for Health and the Global Environment and an assistant clinical professor of psychiatry at Harvard Medical School. In 1980, he co-founded International Physicians for the Prevention of Nuclear War, recipient of the 1985 Nobel Peace Prize. In 2008, Time magazine named him one of the 100 most influential people in the world. Along with Aaron Bernstein, he is the editor of Sustaining Life: How Human Health Depends on Biodiversity (Oxford University Press, 2008). Photo: susanne miller/u.s. fish and wildlife service |
|