A stroll through nearly any American grocery store or pharmacy yields ample proof of the soybean’s increasing role in the U.S. diet. Food packaging offers statements about products’ soy content and the purported associated health benefits. Products such as tofu, soy milk, soy-based infant formula, and meatless “texturized vegetable protein” burgers are widely available. Shelves of dietary supplements and nutraceuticals are stocked with isoflavones, naturally occurring estrogenic compounds found in soy. The general impression is one of certainty that both soy and soy isoflavones deliver many health benefits, including prevention of cardiovascular disease, cancer, and osteoporosis, as well as treatment of menopausal symptoms. The science is less absolute, however, and still evolving.Soy provides a complete source of dietary protein, meaning that, unlike most plant proteins, it contains all the essential amino acids. According to the American Soybean Association, 3.14 billion bushels (85.5 million metric tons) of soybeans were harvested in the United States in 2004. Approximately half of the harvest was exported, and most of the remainder was crushed to produce oil and protein meal for domestic use. An April 2006 report from the USDA Economic Research Service indicates that only a small amount of whole soybeans are used to produce soy foods, and just 2% of soy protein meal is used for human consumption; the rest is used for animal feed.Consumer Attitudes About Nutrition report, 25% of Americans consume soy foods or beverages at least once per week, and 74% view soy products as healthy.The Soyfoods Association of North America reports that U.S. sales of soy foods reached $3.9 billion in 2003, continuing an 11-year trend of 15% average annual increases. According to the United Soybean Board’s 2004–2005 Nevertheless, Americans as a whole still consume very little soy protein. Based on 2003 data from the UN Food and Agriculture Organization, per-capita soy protein consumption is less than 1 gram (g) per day in most European and North American countries, although certain subpopulations such as vegetarians, Asian immigrants, and infants fed soy-based formula consume more. The Japanese, on the other hand, consume an average 8.7 g of soy protein per day; Koreans, 6.2–9.6 g; Indonesians, 7.4 g; and the Chinese, 3.4 g.Traditional soy foods include tofu, which is produced by puréeing cooked soybeans and precipitating the solids, and miso and tempeh, which are made by fermenting soybeans with grains. “Second generation” soy products involve chemical extractions and other processing, and include soy protein isolate and soy flour. These products become primary ingredients in items such as meatless burgers, dietary protein supplements, and infant formula, and are also used as nonnutritive additives to improve the characteristics of processed foods.Soybeans and soy foods contain a variety of bioactive components, including saponins, protease inhibitors, phytic acid, and isoflavones. Isoflavones belong to a class of compounds generally known as phytoestrogens, plant compounds that have estrogen-like structures.The dominant isoflavone in soy is genistein, with daidzein and glycitein composing the remainder. Within soy, isoflavones are almost entirely bound to sugars, producing the respective compounds genistin, daidzin, and glycitin. Soy isoflavones have been linked with numerous health effects, but the strength of the relationships and whether the effects are beneficial are strongly debated.S-transferase, and quinone reductase; and inhibitors of angiogenesis.Soy isoflavones are frequently referred to as weak estrogens, and depending upon the specific circumstance, they can act as agonists, partial agonists, or antagonists to endogenous estrogens (such as estradiol) and xenoestrogens (including phytoestrogens) at estrogen receptors. They are not especially potent, however, and activity varies by tissue concentration, cell type, hormone receptor type, and stage of differentiation. In addition to their estrogen receptor activity, isoflavones may also interfere with steroid metabolism by inhibiting aromatase, hydroxysteroid dehydrogenase, and steroid α-reductase, and by altering the ratio of estradiol metabolites. Soy isoflavones may also act as antioxidants; inhibitors of proteases, tyrosine kinases, and topoisomerases; inducers of Phase I and/or Phase II enzymes such as cytochrome P450s, glutathione in vivo potency from in vitro systems. In vitro systems are valuable for investigating the structure–activity relationships and the mechanisms of isoflavone actions, but in vitro tests have used genistein concentrations that may be five times higher than the peak concentrations seen in human serum, 95% of which occurs as glucuronide conjugate. Animal studies also require careful extrapolations due to how exposure occurs, interspecies differences in metabolism, and comparability of the stage of development at which exposure occurs.Such activities have potential benefits—if they occur in the body. Caution is necessary when predicting Biology of Reproduction linked genistein with effects such as abnormal estrous cycle, altered ovarian function, and infertility in mice.Retha R. Newbold, a supervisory research biologist at the NIEHS, is well aware of these factors. Concerns about genistein’s effects on reproduction and development are due in part to her extensive research in mice. Newbold believes caution is warranted, because her studies, as well as others, have shown that genistein has such effects as inducing uterine adenocarcinoma in mice and premature puberty in rats. A recent study led by biologist Wendy Jefferson in Newbold’s laboratory and published in the October 2005 issue of The original interest in soy was fueled by geographic epidemiology—the observation that populations that consume a lot of soy, particularly those in eastern Asia, have less breast cancer, prostate cancer, and cardiovascular disease, and fewer bone fractures. Additionally, women in these populations report fewer menopausal symptoms, such as hot flashes, and both men and women have a lower incidence of aging-related brain diseases. Since lifestyle can affect chronic disease development, and diet is a major lifestyle factor, traditional Asian diets drew considerable attention.Although initial research overestimated the amount of soy consumed by Asians, the cumulative evidence of numerous biomarker studies has confirmed that their diets are significantly higher in both isoflavones and lignans (another phytoestrogen) compared to the typical Western diet. Studies have further shown that when Asians emigrate to Western nations such as the United States and adopt the prevailing diet, their disease rates change.What’s interesting, says Jay Kaplan, head of comparative medicine at Wake Forest University School of Medicine, is that people who switch to an American-style diet from a traditional diet high in plant protein take on the disease characteristics of the host population, not those of their ancestral population. “It does seem to be something that’s in the environment, and it looks like this reliance on plant proteins is one of these things that goes away after [immigrants have] been here a while,” Kaplan says. “What also goes away is any protection from chronic disease that we ascribe to those populations.”By the late 1990s, the epidemiologic and experimental data seemed strong enough to support recommendations to incorporate soy in the diet. Still, not everyone was convinced.Soy research is complicated because there’s considerable variation in isoflavone exposure among people classified as soy consumers. Agronomic factors  affect a food’s isoflavone profile, as does the way a soy food is processed. For example, soy protein concentrate produced by alcohol extraction may have only 12.5 milligrams (mg) total isoflavones per 100 g, in contrast to the nearly 199.0 mg total isoflavones per 100 g of full-fat roasted soy flour. Additionally, the fact that most of the isoflavones in food occur bound to sugar affects how they are digested.Once genistin enters the digestive tract, it releases its sugar and becomes “free” genistein. Some of this free genistein is absorbed. However, most is reconjugated into glucuronides or sulfates, the primary circulating forms of genistein, which are thought to have either low or no biological activity. Only a very small amount of free genistein escapes conjugation by the liver and circulates in that form.“People need to know that as it occurs in soy and other plant products, genistin is the compound that’s there. The amount of actual genistein is very low, one percent or less probably,” says Michael Shelby, director of the National Toxicology Program’s Center for the Evaluation of Risks to Human Reproduction (CERHR). Key exceptions are fermented products, such as miso and tempeh, which may contain up to 40% free genistein.Several researchers say that figuring out the pharmacokinetics of genistin and genistein is a vital piece of missing information. “It’s a matter of finding out how much genistin is converted to genistein in the digestive system, and that information is not known,” says Jefferson. “I don’t think a lot of this was understood years ago when some of the animal experiments started, and at that time we didn’t have a clear understanding of the metabolism and fate of these chemicals. We did the best we could, as a community, to try to use the compound we thought would be the one we should look at. I think it’s given us some excellent starting types of data, where we know that these compounds are capable of causing reproductive and developmental effects.”According to Thomas Badger, director and senior investigator at the Arkansas Children’s Nutrition Center in Little Rock, however, these effects are seen only under certain experimental conditions that are not likely to occur in humans—and therein lies the crux of the debate. Criticisms of many studies of genistein’s effects on reproduction and development have centered on exposure occurring by injection and consequently bypassing the usual metabolic pathways. There is also disagreement about the use of neonatal mice—commonly used in studies of reproduction and development—as a suitable model for predicting effects in human infants.Despite these criticisms, Newbold stands by her data. “There was some confusion on the fact that in all of our work we have injected genistein,” she says. “We went back and did some of the pharmacokinetics with that to show that the total circulating amounts of genistein are very similar to what’s been reported in feeding rats and also in infants. Metabolism doesn’t have to be the same, but you have to know that the active compounds are getting to the target tissue. Ultimately, a mouse and a rat are not the human, though. You just have to accept it and be as careful with your extrapolations as possible.”Further controversy surrounds the fact that most of the epidemiologic studies of Asian populations involved whole soy foods, but animal and human intervention studies have generally used soy concentrates or isolated isoflavones; some animal studies used pure genistein. This difference may have obscured what the health effects of soy actually are.“I’m reasonably sure that any time you take one of those isoflavones and give it separately, you don’t see the same effects as when all three of the isoflavones of soy are given,” says Kaplan. “Based on everything that we know, the best health effects probably come from the whole isolated soy protein given together. There’s something about the intact product that seems to be bioactive that is not able to be replicated when you begin chopping it up.”Expert Panel Report on the Reproductive and Developmental Toxicity of Genistein, a March 2006 review of the literature on this compound, an expert panel convened by the CERHR scrutinized what has been learned about human exposure to genistein and the associated reproductive and developmental consequences. The most highly exposed adult population was Japanese, with a daily average intake of 0.43 mg per kilogram body weight, which was approximately 10-fold less than the no-effect levels found in rodent studies. Based on the conclusions presented at a meeting held on 15–17 March 2006, the panel found little cause for concern about human exposure to genistein. However, no consideration was made for the amount of genistin found in the diet or how much of it is hydrolyzed in the digestive system to genistein. Further, the panel’s conclusions were not unanimous.In Considerably less attention has attached to daidzein, though there are currently indicators that it may play a larger role than genistein in soy’s apparent beneficial health effects. Like genistein, daidzein in soy exists primarily in linkage with a sugar molecule. This complex, daidzin, is hydrolyzed and the sugar molecule removed in the gut. Daidzein can also be conjugated to glucuronic acid or sulfate in the gut and liver. It may also be converted to equol  by gastrointestinal bacteria. There is considerable variability in individuals’ ability to produce equol, and the metabolic pathways for both genistein and daidzein may vary due to factors such as a person’s particular microflora, intestinal transit time, and current or recent use of antibiotics and other drugs.Thomas Clarkson, a professor of comparative medicine at the Wake Forest University School of Medicine, points out that although soy protein has a very large beneficial effect on cardiovascular health in monkeys, the effects are much less clear in women. Daidzein metabolism may be the key.“Our best clue is that all monkeys are equol producers, but only about twenty-five or thirty percent of women are equol producers,” Clarkson explains. “There’s some suggestion now that those women who are equol producers do derive some cardiovascular benefits. The fact that [the effects are] so profound in monkeys may have to do with the fact that they’re all equol producers, and [those effects] may only be translatable to the women who are equol producers.”in vitro studies that glycitein may be protective of bone. Most glycitein research has focused on determining how to detect the compound, and its estrogenicity and metabolism.There have been only a few studies that have looked exclusively at glycitein, the third soy isoflavone, but those have not been on health effects. There are indicators from a couple of recent Approximately 20–25% of U.S. infants receive at least some soy-based formula in their first year (there are no numbers on how many are exclusively fed soy formula). Unlike soy milk, which is sometimes mistakenly—and tragically—used in its place, soy formula contains soy protein isolate supplemented with additional amino acids, minerals, vitamins, and fats necessary to support infant growth and development. Parents may choose soy formula for babies who are allergic to cow’s milk–based formula or if they themselves do not consume dairy products.Steroid hormones affect myriad processes during development, including the formation of hormone-responsive tissues and organizing and activating effects in the central nervous system. Some researchers are therefore concerned that isoflavones from soy-based infant formula might perturb that system, with long-term consequences.The Lancet, infants fed soy formula were found to receive 28–47 mg of soy isoflavones per day. Isoflavones were detected in blood, showing that infants absorbed the compounds from the intestine. This was not a given, since the infant gut is significantly different from the adult gut and continues to develop through the first year.In a study led by Kenneth Setchell at the Children’s Hospital Medical Center in Cincinnati and published 5 July 1997 in International Journal of Toxicology.Biological effects are plausible but not necessarily detrimental. For example, in a study comparing the short-term, long-term, and multigenerational effects of soy protein isolate, casein, and whey on the health and development of rats, a group led by Badger found that soy protein isolate was protective against chemically induced breast cancer. This study appeared in the 1 May 2001 issue of the Human Reproduction in July 2002, compared infant marmosets fed cow’s milk–based formula with others that were fed soy-based formula. The soy-fed marmosets had comparatively lower testosterone levels and higher numbers of Leydig cells per testis. However, a follow-up study published in April 2006, also in Human Reproduction, indicated no obvious effects on reproduction.In advising caution in feeding infants soy formula, several groups cite a study led by Richard Sharpe at the Centre for Reproductive Biology in Edinburgh, Scotland. The study, published in JAMA. In this study, adults who had been in a controlled feeding study during infancy completed a telephone interview about their health, development, and reproductive history. The only significant differences reported were that women who received soy formula as infants had slightly longer menstrual bleeding and more discomfort than women who had received cow’s milk–based formula. A follow-up letter to the JAMA editor pointed out that both the Strom study and a retrospective epidemiological study published in the April 1990 issue of the Journal of the American College of Nutrition suggested that consumption of soy formula could adversely affect immune function in children.One of the few human studies was led by Brian Strom of the University of Pennsylvania in Philadelphia, in conjunction with the University of Iowa, and published in the 15 August 2001 issue of Expert Panel Report on the Reproductive and Developmental Toxicity of Soy Formula. “The findings for soy formula were that there’s just not enough information to make the call. I’m not surprised by that at all,” says Newbold. “Hopefully, the next step that will come from this is that there certainly will be more research with soy formula and more epidemiology studies. That’s definitely what we’re missing.”More human data are clearly needed, as described in the recent CERHR For their part, both Jefferson and Newbold caution against using their results to determine the safety of soy formula, although they believe their findings of adverse effects in rodents provide strong evidence that concern is warranted. Their findings are not definitive proof that soy formula is harmful, however. “The studies in our laboratory are to determine if these compounds can cause an effect at any dose level,” says Jefferson. “The studies we do in our laboratory were designed to study mechanism, and not specifically intended for risk assessment.”Given the limited evidence for the health effects of soy isoflavones in infants, pediatric and health organizations in several countries suggest caution in feeding soy to infants and young children. If an infant is not receiving breast milk (either its mother’s or a donor’s), cow’s milk–based infant formula is the first recommendation. If there seems to be a problem with that option, parents shouldn’t automatically switch to soy formula, assuming dairy allergy or lactose intolerance. Soybeans are a major allergen, and a significant percentage of children who are sensitive to dairy are also sensitive to soy.However, other experts indicate that soy formula is an adequate source of nutrition for infants with more than 40 years of apparently safe use. “It’s always true that there could be something subtle that we didn’t look for or didn’t know to look for, but so far we haven’t seen any major health problems,” says Susan Baker, a pediatric gastroenterologist at the Children’s Hospital of Buffalo and former chair of the American Academy of Pediatrics Committee on Nutrition. Marisa Salcines, director of communications for the Atlanta-based International Formula Council, which represents infant formula manufacturers, adds that there’s no conclusive evidence for alarm in terms of genistein in soy formula. “There haven’t been any studies that have shown any negative effects in adults who consumed soy-based infant formulas as babies,” she says.To clarify whether or not concerns are justified, Badger is leading the world’s largest longitudinal, prospective study of children comparing soy-based formula, cow’s milk–based formula, and breast milk. During the study, now in its fourth year, children receive multiple in-depth checkups, including assessments of bone development and health, imaging of reproductive tissues, and assessments of brain development and function, metabolism, growth, development, and body composition. The research team aims to enroll 600 pregnant women, whose children will be followed from birth through puberty.Additionally, Walter Rogan, a senior investigator in the NIEHS Epidemiology Branch, is heading the Study of Estrogen Activity and Development. Through pilot studies conducted in late 2004 at the Children’s Hospital of Boston and the Children’s Hospital of Philadelphia, researchers gathered physical, sonographic, and biochemical data from infants fed soy formula, cow’s milk formula, or breast milk. Data analysis is currently under way.Circulation indicated there was little to no effect. The only apparent impact of soy and soy isoflavones on cardiovascular disease risks seems to be a slight reduction in low-density lipoproteins in individuals who had very high levels of cholesterol. An August 2005 report from the DHHS Agency for Healthcare Research and Quality, Effects of Soy on Health Outcomes, also concluded that there was little evidence to support a beneficial role of soy and soy isoflavones in bone health, cancer, reproductive health, neurocognitive function, and other health parameters.On balance it does not seem that soy and its constituent isoflavones have met original expectations. Clinical results with regard to soy’s ability to reduce the risk of cardiovascular disease have been inconsistent; a review in the 21 February 2006 issue of in vitro studies with human breast cancer cells suggest that genistein may induce detoxification enzymes and inhibit growth of both estrogen receptor–positive and estrogen receptor–negative cancers. Additionally, in vitro studies demonstrate that genistein inhibits prostate cancer cell growth, and epidemiologic studies continue to find an inverse relationship between consumption of isoflavone-rich foods and prostate cancer. Rodent models and in vitro systems have suggested beneficial effects on bone density; similar results have not been observed in humans, although clinical trials have shown a promising effect on biomarkers of bone turnover.Nevertheless, there remain tantalizing clues that soy may benefit human health. For example, Although there has been comparatively little research on the effects of soy and isoflavones on cognition and other brain activity, Clarkson says this area may also hold some promise. “Our group has done some work [in monkeys] showing that [soy] modifies serotonin metabolism in a direction that should be useful in the prevention of depression,” he says.Michael R. Adams, a professor of pathology at Wake Forest University School of Medicine, has expanded the scope of the research beyond isoflavones. He is currently looking at one of soy’s protein fractions, 7S, which may have a role in inhibiting the development of atherosclerosis by acting directly on the artery wall rather than on plasma lipids or low-density lipoprotein cholesterol receptors.What most researchers do agree on is that we are only just beginning to truly understand the nature of soy, and that much more research is needed before it is possible to make firm health recommendations. “If you look at nutritional research in general,” Kaplan says, “there are kinds of proteins that are described as being ‘bioactive.’ Most people had assumed that if soy is bioactive, it’s because of the isoflavones. We’re no longer certain of that at all.”


As a species, we pride ourselves on the uniqueness of our brain. But comparisons with other species may tell us how our unique brains evolved As a species, we pride ourselves on the uniqueness of our brain. Relative to our body size, the human brain is bigger than that of any other animal. It may also contain unique structures and patterns of organisation that presumably underlie our intelligence and ability to manipulate our environment. But how did our unique brain originate, and under what selective pressures did it evolve? Some of the answers may lie in the genetic differences that researchers are now uncovering between us and our closest relatives.When we compare our brain to those of other animals, the first thing that strikes us is its size. Human brains weigh on average 1,300 grams; a squirrel brain weighs six grams. Some of this difference is because, as larger animals, we need more brain to run our bodies. However, the brains of our nearest relatives, the great apes, weigh only 300–500 grams, even though their body size is similar to ours . “HumansJust how unique is human brain evolution? Neuroscientist Lori Marino  and her colleagues have used computed tomography to estimate the body and brain size of 36 fossil whale species and have compared these data with those for modern toothed whales. Relative to body size, whales and dolphins have the next biggest brains to us, bigger even than chimpanzees, and, says Marino, “there have been dolphins swimming in the oceans with huge brains for more than 15 million years. We are really the new kids on the block.”Like in humans and other primates, the neocortex in whale brains is huge, but its structure is very different to that of our neocortex. Whales have been independent of other lineages for about 60 million years, notes Marino, and haven't shared a common ancestor with primates for 94 million years. “Nevertheless, during evolution, whales have converged upon very similar capacities and behaviours to those of primates, including a highly developed social structure, which tells us that there is more than one way to evolve a complex intelligence.”Throughout mammalian and primate evolution, there has been a gradual increase in brain size, superimposed with “spikes” of fast growth such as the tripling in human brain size that occurred about 1.5 million years ago, 4 million years after the human lineage diverged from that of the great apes. “Even in the ape lineage, the brain has been expanding but along the human lineage it has really taken off”, says Lahn.In addition, over time, different parts of our brain have increased in size at different rates. The cerebral cortex has expanded more than other areas, and within the cortex, some areas have expanded differentially while others have lagged behind.“Humans sit on the top of the pile when it comes to relative brain size.”Paleoanthropologist Ralph Holloway  uses endocasts to look for macroscopic differences in the brains of our human ancestors. “We fill human fossil skulls with vulcanised rubber and once it has set, we pull it out of the large hole at the base of the skull and the rubber snaps back into the shape of the skull”, Holloway explains. Endocasts are particularly useful for comparing brain sizes, but they also provide information on when the asymmetries that are present in our brain first appeared. These often reflect cerebral specialisation, and Holloway believes that some of the asymmetries he sees in human fossil skulls may indicate when our ancestors acquired language.More details about how the shape of our brain differs from that of our closest living relatives are emerging from the work of neuroscientist Karl Zilles . He prepares magnetic resonance images of monkey, ape, and human brains and then uses a nonlinear elastic algorithm to transform one brain into another . “We knoScientists are also using other techniques to investigate more subtle changes in the organisation of the human brain compared to the brains of other mammals and primates. Indeed, says Holloway, the reorganisation of the brain during evolution has been at least important as its increase in size. Neurobiologist John Allman  and his collaborators, for instance, have discovered that a special type of large spindle-shaped neuron, first described in the early 20th century by Constantin von Economo, is unique to apes and humans and much more numerous in the latter. These neurons are found in brain areas that are implicated in decision making in uncertain situations so, Allman speculates, they may help humans to interact rapidly in complex social situations.per se would not work, brain reorganisation and size increase probably occurred in parallel during human brain evolution. The end result is that the human brain is not just a scaled-up version of a mammal brain or even of an ape brain.A bigger, more complex brain may have advantages over a small brain in terms of computing power, but brain expansion has costs. For one thing, a big brain is a metabolic drain on our bodies. Indeed, some people argue that, because the brain is one of the most metabolically expensive tissues in our body, our brains could only have expanded in response to an improved diet. Another cost that goes along with a big brain is the need to reorganise its wiring. “As brain size increases, several problems are created”, explains systems neurobiologist Jon Kaas . “The most serious is the increased time it takes to get information from one place to another.” One solution is to make the axons of the neurons bigger but this increases brain size again and the problem escalates. Another solution is to do things locally: only connect those parts of the brain that have to be connected, and avoid the need for communication between hemispheres by making different sides of the brain do different things. A big brain can also be made more efficient by organising it into more subdivisions, “rather like splitting a company into departments”, says Kaas. Overall, he concludes, because a bigger brain For natural selection to work, the costs of brain evolution must be outweighed by the advantages gained in terms of fitness. For many years, explains ecological psychologist Robin Dunbar , “people thought that the ability to hunt or forage better was what drove the evolution of our brains. But a better diet had to come before we could grow a bigger brain.” Dunbar believes instead that brain evolution in primates and more generally in mammals “has been driven by the need to manage social relationships, and in primates, in particular, to coordinate coherence in social groups through time and space”. More complex social interactions, he says, mean that individuals are better able to pool resources to solve problems like finding food, and so they survive better.This theory, says Dunbar, is supported by a correlation between social group size and neocortex size across primates and modern humans. Furthermore, during primate brain evolution, the trend has been to add more material to the front than the back of the brain. The front of the brain is where information from the rest of the brain is interpreted, and the capacity to interpret information underlies social interactions, says Dunbar. The number of problem-solving cognitive tasks you can do may well depend on how much frontal lobe volume you have and how it is organised. Just think of how few moves you can run a chess game into the future with a 1980s personal computer compared to a 21st century mainframe machine, he suggests.The human brain is not just a scaled-up version of a mammal brain or even of an ape brain.ASPM  and microcephalin were identified as two causes of microcephaly. Three groups have since reported that both these genes have been under selective pressure during primate evolution. ASPM encodes a protein involved in spindle formation, so it is tempting to think that changes in its sequence might result in an increased rate of cell division and hence brain size. But, cautions Walsh, “we really have no idea yet how or even if ASPM is involved in brain evolution”.Selective pressures like those considered by Dunbar and, before him, by scientists like Holloway work on the raw material of random gene mutations, and molecular biologists now have some clues to the gene changes that may underlie brain evolution. Take brain size, for example . ResearcASPM and microcephalin may be only the tip of the iceberg when it comes to genes that have helped to shape our brains. For example, Walsh has recently reported that deletion of a gene called Nde1 produces mice with very small brains. “Our experiments indicate that the loss of Nde1 causes neurons to mature prematurely. This stops them dividing so the mice end up with small brains”, explains Walsh, who is now investigating whether human NDE1 variants have been positively selected during human evolution.Both Lahn and Walsh believe that Cell paper, Lahn and his colleagues identify several hundred genes that are involved in nervous system biology and show that, as a group, there are significantly higher rates of protein evolution in these genes in primates than in rodents. Protein evolution rates are particularly high in the lineage leading from ancestral primates to humans, notes Lahn, “so some of these genes may regulate brain size and behaviour”. However, he warns, as with ASPM and microcephalin, “definitive proof for this will only come from functional studies, which are difficult to do”.Lahn is also searching for additional candidate genes that might help to explain how our brains evolved. In a recent GLUD2, a retrogene derived from GLUD1, which encodes glutamate dehydrogenase. GLUD2, which first appeared 18–23 million years ago in hominoids, probably immediately picked up a brain-specific promoter and then over the next few million years acquired two critical amino acid changes, explains Kaessmann. These allow GLUD2-encoded glutamate dehydrogenase to work better in the brain than the GLUD1-encoded enzyme. Because glutamate dehydrogenase recycles the neurotransmitter glutamate, the presence of GLUD2 may permit a higher neurotransmitter turnover and greater neuronal activity in hominoid brains than is possible in monkey brains, which lack GLUD2, suggests Kaessmann.For one gene, evidence for an effect on brain function may be emerging. Geneticist Henrik Kaessmann  studies the origin of new genes in primates, in particular genes that arise when a DNA copy of an mRNA transcribed from an existing gene is integrated back into the genome. Usually this new “retrocopy” is not expressed, but if the DNA inserts near an active promoter, it can become a transcribable “retrogene”. This is the origin of GLUD2, be implicated in brain evolution. By contrast, evolutionary neurobiologist Todd Preuss  hopes to identify genes involved in human brain evolution by comparing gene expression patterns in different primates. Preuss, who began training as a paleoanthropologist before turning to neuroscience, has been comparing post-mortem human and chimpanzee brains since the mid 1990s, believing that “if we want to understand human brain evolution, we really have to compare humans with chimpanzees, our nearest relatives”, even though chimp brains have been evolving separately from ours for 5–7 million years. But, warns Preuss, “we have to do these studies now. There are few chimps left and if we lose the opportunity to study them and their brains, we will lose forever a fundamental source of insight into our own species.”Kaessmann plans to search his extensive database of retrocopies in the human genome for other functional genes that could, like To begin with, Preuss used staining techniques that exploit antibodies to examine the neural components of chimpanzee and human brains. Then in 1998, he was asked to collaborate in a microarray project. “My antibody approach was very labour intensive so I jumped at the opportunity to screen 10,000 genes at once”, he says.Preuss and his collaborators now know that more than 100 genes are differentially expressed in chimpanzee and human brains. “Importantly, when we go back into tissue with probes for these gene products, in some cases there are remarkably different spatial patterns of expression in humans, chimps, and macaques”, notes Preuss. “We don't know yet what these differences mean in terms of functional organisation in these different brains but our results open up new and exciting vistas”, particularly since many of the differentially expressed genes have not previously been considered as being potentially involved in brain evolution. The microarray data produced by Preuss and other researchers also indicate that many of the gene expression changes that have occurred during brain evolution involve gene upregulation. For example, there is increased expression of genes involved in metabolism, synaptic organisation, and synaptic function. “All told, it seems that the human brain may be more dynamic than ape or monkey brains”, says Preuss. “The human brain seems to be running hot in all sorts of ways.”As far as understanding how our brains evolved, more questions remain than have been answered. One problem is that we don't really know enough about how our brains differ from those of other mammals and primates, although work by Zilles and others is helping here. We also know very little about how the areas of our brain are physically linked up, and we need to understand that before we can see how we differ from our nearest relatives. And as far as identifying the gene changes that were selected during evolution, although we have several candidates, we don't know how or if these gene variants affect our cognitive abilities. It is one thing, concludes Dunbar, to identify genetic or anatomic differences between human and ape brains, but quite another to know what they mean in terms of actual cognitive processes.


Cardiovascular disease (CVD) is a well-known killer of older people in affluent countries. In developing countries, however, the disease is striking a younger age group. In India, South Africa, Brazil, and the Russian republic of Tatarstan, people aged 35–65 die from CVD significantly more often than counterparts in the United States, according to a report released recently by Columbia University’s Earth Institute.CVD is on the rise in developing nations for the same reasons that made it a killer in the west: a rise in cigarette smoking, a higher-fat diet, and lack of physical exercise. The CVD death rate in developing areas is reminiscent of that experienced in the United States in the 1950s and 1960s before effective public health measures, like warnings about the dangers of smoking and treatment for hypertension, became common. But such measures “have not yet occurred in developing countries, and treatment is often unavailable,” says epidemiologist Stephen Leeder of the University of Sydney in Australia, who coordinated the project while a visiting fellow at Columbia University.Leeder’s team combined available death rate and workforce data from five representative middle- and low-income regions to estimate the economic impact of CVD on society. Their report, released in April 2004, reveals a silent epidemic affecting both women and men of working age.In Tatarstan, CVD deaths among men aged 35–64 have soared 70% in just 20 years. Among women aged 15–34, four times more die from CVD than from pregnancy-related problems—a surprise, given that CVD is rarely considered a woman’s disease in developing nations. China’s CVD death rate currently mirrors that of the United States but is expected to be twice the U.S. rate by 2030, when half of the 9 million projected Chinese CVD deaths will be among people aged 35–64. In Brazilians aged 35–44, the male death rate from CVD is 30% higher and the female death rate 75% higher than for the same age group in the United States. In South Africa, CVD ranks third as cause of death in women and sixth for men.A Race Against Time, refers to a 20-year window of opportunity to tackle the problem. “Younger people can be educated about lifestyle changes and treated with drugs,” says Leeder. If action is not taken now, the health costs in 20 years as these people reach end-stage disease “will be stupendous,” he warns.The report’s title, As world health organizations struggle to finance treatments for infectious diseases such as malaria and AIDS, the report reminds us that “we need to pay attention to chronic diseases like heart disease,” says Daniel Fox, president of the Milbank Memorial Fund, which works with decision makers to bring the best available evidence to bear on health care and public health policy. The report is “analytically tight,” says Fox, and suggests that the economic and social impact of heart disease in the next generation may dwarf that of communicable diseases.


Guidelines for Community Noise, the World Health Organization (WHO) declared, “Worldwide, noise-induced hearing impairment is the most prevalent irreversible occupational hazard, and it is estimated that 120 million people worldwide have disabling hearing difficulties.” Growing evidence also points to many other health effects of too much volume.It’s not difficult for a person to encounter sound at levels that can cause adverse health effects. During a single day, people living in a typical urban environment can experience a wide range of sounds in many locations, including shopping malls, schools, the workplace, recreational centers, and the home. Even once-quiet locales have become polluted with noise. In fact, it’s difficult today to escape sound completely. In its 1999 Noise Effects Handbook that more than 100 million people in the United States are exposed to noise sources from traffic near their homes.The growing noise pollution problem has many different causes. Booming population growth and the loss of rural land to urban sprawl both play a role. Other causes include the lack of adequate anti-noise regulations in many parts of the world; the electronic nature of our age, which encourages many noisy gadgets; the rising number of vehicles on the roads; and busier airports. The U.S. Environmental Protection Agency (EPA) has long identified transportation—passenger vehicles, trains, buses, motorcycles, medium and heavy trucks, and aircraft—as one of the most pervasive outdoor noise sources, estimating in its 1981 Some experts define noise simply as “unwanted sound,” but what can be unwanted for one person can be pleasant or even essential sound to to another—consider boom boxes, car stereos, drag races, and lawn mowers in this context. Sound intensity is measured in decibels (dB); the unit A-weighted dB (dBA) is used to indicate how humans hear a given sound. Zero dBA is considered the point at which a person begins to hear sound. A soft whisper at 3 feet equals 30 dBA, a busy freeway at 50 feet is around 80 dBA, and a chain saw can reach 110 dBA or more at operating distance. Brief exposure to sound levels exceeding 120 dBA without hearing protection may even cause physical pain.Mark Stephenson, a Cincinnati, Ohio–based senior research audiologist at the National Institute for Occupational Safety and Health (NIOSH), says his agency’s definition of hazardous noise is sound that exceeds the time-weighted average of 85 dBA, meaning the average noise exposure measured over a typical eight-hour work day. Other measures and definitions are used for other purposes. For example, “sound exposure level” accounts for variations in sound from moment to moment, while “equivalent sound level” determines the value of a steady sound with the same dBA sound energy as that contained in a time-varying sound.In the United States, about 30 million workers are exposed to hazardous sound levels on the job, according to NIOSH. Industries having a high number of workers exposed to loud sounds include construction, agriculture, mining, manufacturing, utilities, transportation, and the military.Noise in U.S. industry is an extremely difficult problem to monitor, acknowledges Craig Moulton, a senior industrial hygienist for the Occupational Safety and Health Administration (OSHA). “Still,” he says, “OSHA does require that any employer with workers overexposed to noise provide protection for those employees against the harmful effects of noise. Additionally, employers must implement a continuing, effective hearing conservation program as outlined in OSHA’s Noise Standard.”Meanwhile, there is no evidence to suggest things have gotten any quieter for residents since the EPA published its 1981 handbook. “For many people in the United States, noise has drastically affected the quality of their lives,” says Arline L. Bronzaft, chair of the Noise Committee of the New York City Council of the Environment and a psychologist who has done pioneering research on the effects of noise on children’s reading ability. “My daughter lives near La Guardia airport in New York City, and she can’t open a window or enjoy her backyard in the summer because of the airplane noise.”secondhand noise is increasingly used to describe noise that is experienced by people who did not produce it. Anti-noise activists say its effect on people is similar to that of secondhand smoke. “Secondhand noise is really a civil rights issue,” says Les Blomberg, executive director of the Noise Pollution Clearinghouse, an anti-noise advocacy group based in Montpelier, Vermont. “Like secondhand smoke, it’s put into the environment without people’s consent and then has effects on them that they don’t have any control over.”Indeed, the term Secondhand noise can also have a negative effect in the workplace. “Workers in the construction trades get exposure to noise not just from what they are doing but also from what is going on around them,” says Rick Neitzel, director of communications for the National Hearing Conservation Association. “Electricians, for example, have a reputation as being a member of a quiet trade, but if they work all day next to a laborer who is using a jackhammer, it’s going to have a harmful effect.”Even disregarding other people’s noise, there are any number of household tools and appliances that can produce harmful sound levels in the comfort of one’s own home. According to the fact sheet “Noise in the Home” produced by the League for the Hard of Hearing, dishwashers, vacuum cleaners, and hair dryers can all reach or exceed 90 dBA.Our modern industrialized society has spawned ubiquitous entertainment and sports industries with their boom boxes, “personal stereos” (Gap Kids now even offers a jacket with a built-in radio and speakers conveniently attached right in the hood), surround-sound movie theaters, loud TV commercials, and even louder commercials at sports stadiums crammed full of thousands of noisy fans. In drag racing, a growing international sport, a German team of audio engineers set an earsplitting record of 177 dB–sound pressure level in 2002. Popular “boom cars” equipped with powerful stereo systems that are usually played with the volume and bass turned up abnormally high and the car windows rolled down can hit 140–150 dBA. Listening to music at a level of 150 dBA would be like standing next to a Boeing 747 airplane with its engines at full throttle, according to statistics provided by Noise Free America, an anti-noise advocacy group.Even the countryside is not immune to the impact of noise pollution. According to the New York Center for Agricultural Medicine and Health in Cooperstown, a staggering 75% of farmworkers have some kind of hearing problem, largely the result of long-term exposure to loud equipment.The United States is not the only country where noise pollution is affecting the quality of life. In Japan, for instance, noise pollution caused by public loudspeaker messages and other forms of city noise have forced many Tokyo citizens to wear earplugs as they go about their daily lives. In Europe, about 65% of the population is exposed to ambient sound at levels above 55 dBA, while about 17% is exposed to levels above 65 dBA, according to the European Environment Agency.“The noisy problems associated with air travel are concentrated in communities around airports, whereas motorways or high-speed trains—traveling, for instance, from north to south Europe—have the potential to disturb thousands of people living along the route day after day,” says Ken Hume, a principal lecturer in human physiology at the Manchester Metropolitan University in England.Noise is indeed everywhere, and experts expect no decrease in noise levels, given the powerful impact of technology on modern life. “In the past three decades, we have built noisier and noisier devices that are not subject to any regulations,” Blomberg says. “Think about it. The car alarm is a seventies invention, as is the leaf blower. The stereo sound systems we have in our cars are much louder than the sound system the Beatles used for their concerts in the sixties. All they had back then were three-hundred-amp speakers.”Numerous scientific studies over the years have confirmed that exposure to certain levels of sound can damage hearing. Prolonged exposure can actually change the structure of the hair cells in the inner ear, resulting in hearing loss. It can also cause tinnitus, a ringing, roaring, buzzing, or clicking in the ears. The American Tinnitus Association estimates that 12 million Americans suffer from this condition, with at least 1 million experiencing it to the extent that it interferes with their daily activities.NIOSH studies from the mid to late 1990s show that 90% of coal miners have hearing impairment by age 52—compared to 9% of the general population—and 70% of male metal/nonmetal miners will experience hearing impairment by age 60 . Neitzel says nearly half of all construction workers have some degree of hearing loss. “NIOSH research also reveals that by age twenty-five, the average carpenter’s hearing is equivalent to an otherwise healthy fifty-year-old male who hasn’t been exposed to noise,” he says.“Noise has an insidious effect in that the more exposure a person has to noise, the more the hearing loss will continue to grow,” says Josara Wallber, disabilities services liaison for the National Technical Institute for the Deaf in Rochester, New York. “Hearing loss is irreversible. Once hearing is lost, it’s lost forever.”William Luxford, medical director of the House Ear Clinic of St. Vincent Medical Center in Los Angeles, points out one piece of good news: “It’s true that continuous noise exposure will lead to the continuation of hearing loss, but as soon as the exposure is stopped, the hearing loss stops. So a change in environment can improve a person’s hearing health.”For many young people, changing their environment and their behavior would be a wise and healthy move. That’s because audiologists are fitting more and more of them with hearing aids, says Rachel Cruz, a research associate at the House Ear Clinic. She says audiologists are blaming this disturbing development on youth’s penchant for listening to loud music, especially with the use of headphones.Pediatrics, researchers from the Centers for Disease Control and Prevention reported that, based on audiometric testing of 5,249 children as part of the Third National Health and Nutrition Examination Survey, an estimated 12.5% of American children have noise-induced hearing threshold shifts—or dulled hearing—in one or both ears. Most children with noise-induced hearing threshold shifts have only limited hearing damage, but continued exposure to excessive noise can lead to difficulties with high-frequency sound discrimination. The report listed stereos, music concerts, toys (such as toy telephones and certain rattles), lawn mowers, and fireworks as producing potentially harmful sounds.Research is catching up with this anecdotal evidence. In the July 2001 issue of For the baby boom generation, on the other hand, a change of environment may be too late. “Many baby boomers began losing their hearing when the amplification of popular music came into vogue in the nineteen sixties,” says Cruz. “We are starting to see that a lot of musicians and audio engineers who have been involved with popular music for a long time are having hearing problems.” Cruz is gathering data for a research study to examine how these professionals’ occupational sound exposures affect their hearing over a span of years.Guidelines for Community Noise, “these health effects, in turn, can lead to social handicap, reduced productivity, decreased performance in learning, absenteeism in the workplace and school, increased drug use, and accidents.”The effects of sound don’t stop with the ears. Nonauditory effects of noise exposure are those effects that don’t cause hearing loss but still can be measured, such as elevated blood pressure, loss of sleep, increased heart rate, cardiovascular constriction, labored breathing, and changes in brain chemistry. According to the WHO Journal of the Acoustical Society of America. The results showed that exposure to noise caused stomach contractions in healthy human beings. Reports on noise’s nonauditory effects published since that pioneering study have been both contradictory and controversial in some areas.The nonauditory effects of noise were noted as early as 1930 in a study published by E.L. Smith and D.L. Laird in volume 2 of the Archives of Environmental Health found no significant data suggesting an effect of noise on fetal development in pregnant women who lived near airports. But in the October 1997 issue of Pediatrics, the Committee on Environmental Health of the American Academy of Pediatrics published a policy statement based on a review of research on the potential health effects of noise on the fetus and the newborn. The committee concluded that excessive noise exposure in utero may result in high-frequency hearing loss in newborns and further that excessive sound levels in neonatal intensive care units may disrupt the natural growth and development of premature infants. It recommended that noise-induced health effects on fetuses and newborns are clinical and public health concerns that merit further study.Data pertaining to whether noise can increase the risk of damage to the fetus is a case in point. A study published by L.D. Edmonds, P.M. Layde, and J.D. Erickson in the July–August 1979 issue of the Environment and Behavior, Cornell University environmental psychologists Gary Evans and Lorraine Maxwell reported that the constant roar of jet aircraft could cause higher blood pressure, boosted stress levels, and other effects with potential life-long ramifications among children living in areas under the flight paths of airport.Studies have revealed that as children grow they are exposed to sounds that can threaten their health and cause learning problems. For instance, in the September 1997 issue of Archives of Environmental Health, a team of government and university researchers concluded that exposure to sound “acts as a stressor—activating physiological mechanisms that over time can produce adverse health effects. Although all the effects and mechanisms are not elucidated, noise may elevate systolic blood pressure, diastolic blood pressure, and heart rate, thus producing both acute and chronic health effects.”Other human and animal studies also have linked noise exposure to chronic changes in blood pressure and heart rate. For example, in the July–August 2002 issue of the Environment and Behavior, were that students on the quieter side performed better on reading tests, and by sixth grade they were a full grade point ahead of the students in the noisier classrooms.Noise has also been shown to affect learning ability. In 1975 Bronzaft collaborated on a study of children in a school near an elevated train track that showed how exposure to noise can affect children’s reading ability. Half of the students in the study were in classrooms facing the train track and the other half were in classrooms in the school’s quieter back section. The findings, published in the December 1975 issue of Journal of Environmental Psychology found that children’s reading scores improved after these interventions were put in place. “After we did the study, more than twenty-five other studies were done examining the effect of noise on children’s learning ability,” Bronzaft says. “They have all found the same thing to be true: noise can affect children’s learning.”Bronzaft and the school principal persuaded the school board to have acoustical tile installed in the classrooms adjacent to the tracks. The Transit Authority also treated the tracks near the school to make them less noisy. A follow-up study published in the September 1981 issue of the Noise Effects Handbook that surveys taken in communities significantly affected by noise indicated that interruption of sleep was the underlying cause of many people’s complaints. Research has shown that unwanted sound is most annoying at the times when people expect to rest or sleep, that it can interrupt or delay sleep, and that it can have subtle effects on sleep, such as causing shifts from deeper to lighter sleep stages. “The research is pretty solid that noise can prevent people from getting a good night’s sleep,” Hume says. “I believe that sleep deprivation can have negative health effects when it becomes a chronic problem.”The EPA reported in the Worldwide, airports have become a flash point for community frustration over noise pollution. In September 2002, officials at the Frankfurt am Main Airport in Germany received 56,330 noise-related complaints, a 30% increase over the same month in 2001. The same year, residents living near a rural airport outside London, England, were submitting 100 petitions daily, objecting to proposals for three new runways at the site.In March 2003, representatives from eight neighborhoods in Portland, Oregon, showed up for a city council hearing convened to discuss dozens of expansion projects for Portland International Airport. The airport was already a busy one: in 2002 it handled 12.2 million passengers and about 29,000 containers of air cargo. “The impacts are tremendous on the neighborhoods under the flight paths,” testified one neighborhood representative, Jean Ridings. “People move in and move [right back] out. It’s becoming a disaster.” In response, the airport has initiated a multiyear, multimillion-dollar effort to study the sound impact of the airport, which locals hope will lead to a plan to reduce airport noise.Noise Free America is seeking to file a class-action lawsuit against the makers of boom car equipment. Ted Rueter, Noise Free America’s director and an assistant professor of political science at DePauw University in Greencastle, Indiana, says one group member has written a legal brief on the topic and has approached several public-interest law firms seeking representation, with no takers so far. Rueter says Noise Free America will continue to pursue the suit.A lot of money is being made from disturbing the peace, charges Mark Huber, communications director for Noise Free America. “By using paid lobbyists in Washington, D.C., and in state legislatures, the automobile and entertainment industries are quietly removing obstacles protecting the public against noise,” Huber says. “Try to get a noise control law passed through a state legislature and see what happens. We tried to get a boom car law enacted in the Virginia General Legislature, but right here in Richmond there are at least fifty car clubs, all of which are politically active. So our legislation disappeared.”Stephen McDonald, vice president of government affairs for the Washington, D.C.–based Specialty Equipment Market Association (SEMA), denies that any powerful lobby exists and is working against the best interests of society. SEMA represents manufacturers, distributors, retailers, and installers of specialty automotive equipment, including boom car equipment. “Our prime focus is representing the interests of businesses that sell exhaust systems,” McDonald says. “But that doesn’t mean we want the products to increase noise to a level where it becomes objectionable. We do need to strike a balance, though, between what is acceptable for a neighborhood and what’s fair to people who want to customize their cars.”Anti-noise activists say that Europe and several countries in Asia are more advanced than the United States in terms of combating noise. “Population pressure has prompted Europe to move more quickly on the noise issue than the United States has,” Hume says. In the European Union, countries with cities of at least 250,000 people are creating noise maps of those cities to help leaders determine noise pollution policies. Paris has already prepared its first noise maps. The map data, which must be finished by 2007, will be fed into computer models that will help test the sound impact of street designs or new buildings before construction begins.In the United States, the Noise Control Act of 1972 empowered the EPA to determine noise limits to protect the public health and welfare, and to establish a noise control office. Congress did establish the Office of Noise Abatement and Control (ONAC), as well as federal standards for business, industries, and communities, and it did begin researching the effects of sound exposures. In 1982, however, the Reagan administration defunded the office. “We are no longer doing research on noise,” says Kenneth Feith, an EPA senior scientist and policy advisor. “We just don’t have the money or staff to do it.”Activists believe that closing the ONAC has had a tremendous negative effect at the state and local level. “The U.S. has long since given up its lead in regulating noise, and because of that there has been no consistency in implementing local noise regulations,” Huber says. The Noise Control Act, though still on the books, is essentially toothless.In the mid-1990s, people in the borough of Queens, New York, who lived under the flight paths of La Guardia Airport, took their concerns about noise to Representative Nina Lowey (D–NY). “I could see that noise is a serious public health issue, and so I decided to do something about it,” Lowey says. In 1997 the congresswoman introduced legislation that’s become known as the Quiet Communities Act (HR 536), which provided for the refunding of the ONAC and for $21 million to be spent annually on noise reduction. Among other measures, the money would be used to carry out a national noise assessment program to identify trends in noise exposure and response, develop and disseminate information and public education materials on the health effects of noise, and establish regional technical assistance centers, which would use the resources of universities and private organizations to assist state and local noise control programs.“More and more communities are being affected by airports, trains, and railways,” Lowey says. “We need a national office to coordinate policy. That’s common sense to me. The federal government has to play a larger role on the noise issue. Otherwise, we will continue to lag behind other parts of the world in combating noise.” While Lowey remains optimistic that the legislation will eventually pass, other sources doubt that it will happen, noting that the proposed legislation has been introduced and rejected several times.Activists in other countries say they too want the United States to play a more leading role on the noise issue. “Re-establishing the ONAC would be a huge move in the right direction,” says Hans Schmid, the Vancouver, Canada–based president of the Right to Quiet Society. “That will show that the United States is serious about the noise issue. If the United States leads, other countries, especially Canada, will follow.”But as in other areas of environmental health, merely having a more powerful government agency in place that can set more regulations is not the ultimate answer, according to other experts. Regulations provide an important foundation, Stephenson says, but better education of workers, consumers, businesses, and citizens is critical. “We’ve found that in some factories as many as one-third of the workers who have significant hearing loss don’t wear hearing protectors, even though the factory has a comprehensive hearing conservation program in place,” he says.Bronzaft stresses that governments worldwide need to increase funding for noise research and do a better job coordinating their noise pollution efforts so they can establish health and environmental policies based on solid scientific research. “Governments have a responsibility to protect their citizens by curbing noise pollution,” she says.Feith agrees. “The EPA had a successful educational program in the nineteen seventies in which we went to schools and educated students about noise,” he says. “When students took the message home, they helped increase the sensitivity to the noise issue. We need more programs like that to educate the public about noise.”American Journal of Nursing showed that peak noise levels during the clinic’s morning shift change rivaled the excruciating sound of a jackhammer. The study further showed that a few simple changes—for example, holding staff reports at shift change in an enclosed room (rather than at the nurses’ station) and replacing roll-type paper towel dispensers with quieter models—reduced peak noise levels at shift change by 80%.In the meantime, some facilities are doing what they can to help themselves to a quieter environment. Although peace and quiet are essential prerequisites for a healing environment, a Mayo Clinic study published in the February 2004 issue of the Similarly, the din of overhead pagers, which can reach 80 dBA, inspired the developers of the Woodwinds Health Campus in Woodbury, Minnesota, to build the facility with a staff location sensor and badge system, among other sound-friendly features. Staff can be located in just about any area of the Woodwinds campus without being paged. “We have developed an innovative approach to reducing noise in our hospital while fostering a healing environment,” says Cindy Bultena, executive lead of healing and clinical coordination for Woodwinds. “Our change sounds simple enough, but it’s a very radical one for hospitals.”By delivering their patients and staff from decibel hell, facilities like Woodwinds and the Mayo Clinic have scored one small victory in the ongoing battle against noise pollution. Their initiative, moreover, shows that given the pervasiveness and harmful effects of noise, governments, communities, and organizations worldwide will need to be creative and aggressive in addressing what will certainly continue to be one of the 21st century’s most important environmental health issues.


Edited by David Naguib Pellow and Robert J. BrulleCambridge, MA:MIT Press, 2005. 339 pp. ISBN: 0-262-16233-4, $25Over the past 18 years, hundreds of books have been published on the environmental justice movement (EJM); however, this is one of the first books to initiate a comprehensive dialogue that critiques strategies, tactics, and discursive frames; examine issues of organizational structure, governance, and resource base; assess goals and outcomes; and pose questions challenging academics and activists to consider where the movement has been and where it may go.The EJM—which emerged in the late 1980s from struggles within communities of color and low-income communities that have been disproportionately affected by pollution—is characterized by editors Pellow, an activist–scholar who has published widely on EJ, and Brulle, an associate professor of environmental policy, as “a political response to the deterioration of the conditions of everyday life as society reinforces existing social inequities while exceeding the limits to growth. Thus the EJM laid a foundation for environmental and social justice politics in the twenty-first century.”The heart and strength of these essays by academics, EJ practitioners, and advocates is the challenge to engage foundational concepts of the EJM that most serious observers and activists have been loath publicly to address. Yet 15 years since the historic first People of Color Environmental Leadership Summit, one reads this assessment and analysis and wonders why it has taken so long to begin this important inquiry.The editors’ opening chapter succinctly summarizes literature on inequality, social justice movements, and environmental degradation, and presents provocative conclusions. Although Pellow and Brulle note that the EJM has affected the direction of environmental policy, research, and activism and that the EJM has had its “clearest victories” leading local community struggles, they question whether the EJM has achieved its goals and conclude that the “outlook is not positive.” They issue a challenge, echoed by the authors, to the EJM to “complement its well-honed acumen for opposition to unsustainable projects to a concrete vision and plan of action for construction and protection of sustainable communities”—a challenge that is being met by many EJ organizations.The collection, targeted to scholars, theorists, practitioners, and activists, has three sections. In the first, “Environmental Quality and Justice: Progress or Retreat?” Bryant and Hockman compare the Civil Rights and EJ movements. Some chapters break the chain of synergy and some authors’ conclusions contradict others, but Benford’s “Half-Life of the Environmental Justice Frame: Innovation, Diffusion, and Stagnation” complements other authors in this book with his provocative argument that the “EJ frame suffers from stagnation as a result of its diffuse conceptualization, the many issues it seeks to address, the subordination of environmentalism to human justice, and its failure to embrace and articulate revolutionary solutions.” His argument needs more research and documentation to bolster his conclusion that the EJM’s “power lies in its capacity to disrupt the system rather than to reform it.”Section 2, “New Strategies for Achieving Environmental Justice,” focuses on energy activism, sustainable and just food systems, case studies of collaborative problem solving, and research findings that the governance structure of EJ groups does not reflect its democracy frame. Brown offers lay-driven efforts to reframe social conceptions of health through the asthma/air quality paradigm, and Targ argues for a state-level comprehensive approach to EJ to address issues and approaches across agency jurisdictions. Pena urges that the EJM advance “exploration of autonomy”—self-governance of environmental management in local places—versus the struggle against “toxic racism and its rampant inequalities of place and power.”The third section, “Environmental Justice and the Challenge of Globalization,” highlights South African perspectives, global activism initiatives, and the contrast between the goal of environmental sustainability, management of natural resources, and that of the EJM, human justice, wherein the natural environment is important only “inasmuch as it can be seen in terms of human justice.”Brulle and Pellow conclude by advising EJ scholars to balance documentation of problems with a solution orientation, provide a stronger class analysis, and heed more of the links between EJ research and the literature on social movements. They warn EJ activists that forging a national agenda could deprioritize grassroots base building and that the divide between mainstream environmental groups and the EJM must be addressed more productively. They advise EJ groups to build a greater indigenous base of financial support and to appeal to a broader base of the population by addressing its race-based focus to be more inclusive of class, gender, working-class whites, and nation inequalities.This book asks serious questions that have been raised by the EJM itself and continue to challenge its activists. Although this collection can be fascinating, there are some facile recommendations and observations made without sound basis. Nevertheless, this book is a vital addition to the literature, and it catalyzes a critical dialogue on our environmental future.


If we agree that complex life evolved ultimately from single-celled organisms, how do we explain the origins of the cell itself? A physicist, a chemist, and a mathematician are stranded on a desert isle, when a can of food washes up on the beach. The three starving scientists suggest, in turn, how to open the can and ease their hunger. The physicist suggests they hurl it upon the rocks to split it open, but this fails. The chemist proposes they soak it in the sea and let the salt water eat away at the metal; again, no luck. They turn in desperation to the mathematician, who begins, “Assume we have a can opener….”When discussing the evolution of life, biologists can often sound a bit like that mathematician. Beginning with a single cell, Darwinian evolution provides a simple, robust, and powerful algorithm for deriving all the astonishing richness of life, from bacteria to brains. Natural selection and other evolutionary forces, acting on surplus populations of replicating cells and multicellular organisms, lead inevitably to evolution and adaptation. Give biologists a cell, and they'll give you the world. But beyond assuming the first cell must have somehow come into existence, how do biologists explain its emergence from the prebiotic world four billion years ago?The short answer is that they can't, yet. But this question may be a little closer to being answered as new money enters the field, and two new discoveries provide support for two competing models of prebiotic evolution.While the past half century has seen an explosion of knowledge about the evolution of life after it began, there has been relatively little progress in the past half century on how it began—the so-called origin question. In part, the problem is financial: research money has flooded many other areas in biology, but remains in short supply in this one. “The funding is a big part of it,” says Jack Szostak, a Howard Hughes investigator and Professor of Genetics at Harvard Medical School. As a result, there is a shortage of researchers willing to commit their professional careers to finding out how life began. “This is a risky field to be involved with. The problems are hard. You can train students, but there may not be jobs waiting for them afterwards.” To that end, Harvard University recently announced a plan to fund origin-of-life research to the tune of one million dollars per year, which Szostak says is a good start.Beyond assuming the first cell must have somehow come into existence, how do biologists explain its emergence from the prebiotic world four billion years ago?But finding the answer to the origin question will require not only money but also progress in understanding how the most basic of biological molecules were put together before life began, how they became organized and self-sustaining, and how they developed into the membrane-bound cells that are our ancestors. Scientists have come a long way from the early days of supposing that all this would inevitably arise in the “prebiotic soup” of the ancient oceans; indeed, evidence eventually argued against such a soup, and the concept was largely discarded as the field progressed. But significant problems persist with each of the two competing models that have arisen—usually called “genes first” and “metabolism first”—and neither has emerged as a robust and obvious favorite. Now, two papers published in mid-2005 offer each camp some encouragement.Some 50 years ago, Stanley Miller, then a graduate student at the University of Chicago and now in the Department of Chemistry at University of California at San Diego, got the field of origins research started with a bang—literally. He passed high-voltage electric sparks—a stand-in for lightning—through a gaseous mixture of water, methane, hydrogen, and ammonia, thought to be the major constituents of the ancient atmosphere. The liquid in the reaction flask eventually became a bouillon-like mix of amino acids and other small organic molecules. Miller's results predicted that, over time, the early oceans would have become a rich prebiotic soup, replete with amino acids, nucleic acids, and sugars. His results implied it was only a matter of time before these building blocks combined to form complex polymers and ultimately a replicating cell.In the beginning, according to the so-called genes-first camp, was a single RNA molecule, both code and catalyst. Such a “replicase” would have catalyzed its own replication, and also provided the template on which the copy was made.“The initial Miller experiment was earth-shaking,” says Harold Morowitz, Professor of Biology at George Mason University, and a long-time theorist and researcher in this area. The suggestion that random chemistry could produce the molecules of life “held the field for a long time.” But later calculations appeared to show that the early atmosphere contained much more carbon dioxide and much less hydrogen than Miller's model required, and correcting these concentrations cast doubt on the likelihood that complex molecules would form in abundance Where, then, might organic precursors have come from? There is some, albeit scant, evidence for their arrival on comets colliding with the earth, but there is little enthusiasm for this as a solution. Finally, there is no geologic evidence, in either sediments or metamorphic rocks, that such a soup ever existed.In the early 1980s, just as Miller-type chemistry was falling out of favor, RNA emerged as the rising star of origin-of-life research, based on a startling discovery. Up to this point, evolution appeared to have a severe chicken-and-egg problem: information-bearing DNA codes for protein, but catalytic proteins are essential to make DNA. That the two could have arisen independently but still work in concert seemed highly unlikely. But RNA, which was well-known in its role as temporary information carrier, also turned out to be catalytic. Indeed, a host of functions in modern cells that were once thought to be the province of proteins are instead supervised by catalytic RNA. It is only a small intellectual leap from here back to an “RNA world,” in which RNA, not DNA, is the molecule of heredity, and RNA, not protein, is the catalytic engine of the cell. In the beginning, according to the so-called genes-first camp, was a single RNA molecule, both code and catalyst. Such a “replicase” would have catalyzed its own replication, and also provided the template on which the copy was made.Work by Jack Szostak of Harvard University has lent support to this elegant model. He has shown that certain catalytic RNAs can, indeed, join smaller RNA sequences together, hinting at the potential for self-replication. Given the right starting conditions, such a self-replicating RNA might increase its number at the expense of the “lifeless” ones surrounding it. Successive rounds of copying, with minor mutations, could lead the original replicator to acquire new abilities. Life, Szostak speculates, “starts simple, beginning with one gene, probably a replicase, and accretes additional functionality over time.”It is a highly appealing concept, and has driven a great deal of good research. But how would the original replicase arise? James Ferris, Professor of Chemistry at Rensselaer Polytechnic Institute, has discovered that on the surface of montmorillonite, a common clay, activated RNA nucleotides—the monomeric building blocks of the RNA polymer—will spontaneously link together to form longer chains. While the sequences of these products are entirely random, Szostak has shown that within such a random pool of RNAs, some are likely to be catalytic. Szostak has also recently shown that replicating RNAs inside a lipid membrane vesicle cause the vesicle to grow, mimicking behavior of actual cells.To date, none of the models have proposed a solution to one of the more vexing origin problems: chirality. Three-dimensional molecules such as sugars and amino acids can exist in two mirror-image forms, like left and right hands (chiros is Greek for hand). Any nonbiological synthesis of such molecules, as would have occurred before life arose, produces equal amounts of each type. Nonetheless, modern cells use exclusively left-handed amino acids and right-handed ribose sugars, and interference from the wrong kind shuts down biological reactions. How could chiral life arise in the presence of so much interference?“It's a serious problem,” Orgel admits, “but not an overwhelmingly serious one.” Orgel suggests that one of several possible solutions may be chance, a “frozen accident” that brought together, and kept together, molecules of the right chirality. Such an accident is perhaps not so unlikely, says Martin, who calculates that a mixture of every possible left- and right-handed combination of a 25–amino acid peptide (amino acid chain) would weigh 25 kilograms. “Any smaller sample is imperfect,” he says.Martin also points out the problem may be a bit easier than it seems, since the chirality of a molecule such as a sugar is usually maintained as that molecule wends its way through a metabolic pathway. An enzyme at the head of that pathway could act as a “filter,” allowing only those molecules of the correct chirality to enter, thus fixing chirality for that pathway and others that branch off of it. Exactly this feature is seen in the central metabolic pathway for sugar formation found in all cells.But working back even further, where do the nucleotides come from to form these chains? Here we come up against the “can opener” problem on the molecular level. “The biggest concern about the RNA world is that there has been no convincing prebiotic creation of the activated monomers” in any plausible prebiotic world, says Ferris. Despite years of experiments with dozens of different strategies, no one has figured out how to make this most essential of starting ingredients for an RNA world. “There is a growing realization that we may need to look beyond RNA,” Szostak says, to molecules whose chemistry is a bit more tractable, such as a peptide nucleic acid (PNA), a synthetic amino acid–nucleotide hybrid. These original replicators might then have given way to RNA, says Leslie Orgel, senior fellow and research professor at the Salk Institute of Biological Studies.The case for PNA is weak, though. While modern cells still bear traces of a catalytic RNA world within them, “there is absolutely nothing that I know of to suggest there is evidence for PNA or other such molecules in present cells,” says Orgel. If they ever contributed to the development of life, all traces of their existence appear to have been wiped clean.Whether the original replicator was RNA or PNA or some other molecule, any genes-first model relies on an abundance of building blocks in the environment, a requirement that seems to depend on the discounted idea of Miller's prebiotic soup. But in June of 2005, the prebiotic soup got a new lease on life. New calculations appear to show that there was considerably more hydrogen in the early atmosphere than once thought. “This could resurrect Miller's chemistry,” says Orgel. Nonetheless, “there is still an enormous way to go” to get the full set of RNA precursor molecules.In 1988, even while the RNA world was enjoying its intellectual honeymoon, a German biochemist and patent attorney, Günther Wächtershäuser, proposed a radical alternative theory of the origin of life based on, of all things, fool's gold. Iron disulfide—pyrite or fool's gold—can catalyze a variety of crucial biochemical reactions. There are iron sulfide or iron–nickel sulfide clusters at the heart of several ancient and vital enzymes in use in all cells today. Wächtershäuser proposed that the earliest living system was not a nucleotide-based replicator but a mineral-based metabolizer, converting simple and abundant inorganic compounds—carbon dioxide, hydrogen sulfide—into more complex organic ones on the surface of a pyrite crystal, probably at deep-sea hydrothermal vents.This metabolism-first model has a strong champion in Harold Morowitz, who paints the two major models for life's origin as “heaven and hell.” Miller-type scenarios, including the genes-first model, rely on a wealth of precursors raining down from above. The standard model of the RNA world, he says, “requires an environment that is impossibly improbable.” The alternative is a much smaller set of molecules, at much higher concentrations, bubbling up from below. “I really like theories that go from simplicity to complexity,” Morowitz says.The possibility that metabolism first began at hydrothermal vents has been advanced most recently by Michael Russell, Research Professor of Geology at the Scottish Universities Environmental Research Centre in Glasgow, and William Martin, Professor at the University of Düsseldorf. Russell and Martin propose that life's metabolism developed not on a two-dimensional pyrite surface but within tiny cavities lined with iron monosulfide, through which percolated an energy-rich mix of hydrogen and carbon dioxide dissolved in seawater.The standard model of the RNA world...“requires an environment that is impossibly improbable.” The alternative is a much smaller set of molecules, at much higher concentrations, bubbling up from below.In the early 1980s, Russell discovered fossil fields of iron sulfide “chimneys,” formed on the ocean floor 350 million years ago  and 2. UAnd unlike the 400 °C water spewing out of a black smoker, the water flowing up through these vents was much cooler, not much more than 100 °C. Outside the chamber, the ocean would have been much cooler still, and more acidic and more oxidized than the solution within, creating a set of strong temperature and electrochemical gradients across the microscopically porous surface of the chamber. “Life loves to live at the gradients,” says Russell.The slow trickle of hydrogen and carbon dioxide through such chambers and across the iron sulfide catalyst promotes formation of acetate, according to Russell and Martin. Acetate is a key intermediate in virtually all biosynthetic pathways, and in modern cells, enters these reactions tethered to sulfur. In modern bacteria, the two enzymes that make acetate depend on a catalytic core of iron, nickel, and sulfur, arranged almost exactly as they are in the free mineral itself. “In other words,” Russell and Martin have written, these enzymatic metal clusters “are not inventions of the biological world, rather they are mimics of minerals that are indisputably older, and which themselves have catalytic activity in the absence of protein” .These chambers also suggest a radical solution to a heretofore stubborn problem, one with no other obvious resolution. Modern cells without nuclei are grouped into two domains, the Eubacteria and the Archaebacteria. These ancient lineages share the same energy metabolism and the same genetic code, presumably reflecting a single common ancestor. But they differ profoundly in how they synthesize the lipids in their membranes. One explanation, which Martin dismisses, is that the common ancestor had a membrane, probably similar to the eubacterial structure, and the archaebacterial ancestor “had to completely reinvent its cell wall chemistry.” Such proposals are “completely decoupled from microbial physiology,” he says. The alternative favored by Russell and Martin is that these lipid differences reflect a divergence in the two lines after the last common ancestor already had its carbon biochemistry and genetic code intact, but before the development of lipid membranes. The chambers served as the original cell compartment, and were only replaced by lipids after the eubacterial and archaebacterial lines split.This metabolism-first model is not an alternative to life based on RNA...But it does propose that geology at hydrothermal vents provided the structure in which life emergedRussell and Martin's model also provides a solution to another thorny issue in jump-starting life, that of concentration. An essential feature of all cells is their ability to maintain high concentrations of materials that are in short supply in the world around them. In the absence of a cell membrane, how did proto-life forms collect raw materials, and prevent products from dissipating into the vastness of the environment around them? Russell's chambers solve this problem in essentially the same way modern cells do, with an external boundary that is permeable to small reactant molecules, but much less so to larger product ones. In Russell's and Martin's scenario, then, the stable metabolism that developed within these chambers eventually gave rise to a genetic system, probably dependent on RNA, which encoded simple proteins, probably through direct accretion of RNA and amino acids on the surface of a mineral catalyst. Finally, these proto-organisms developed membranes, completing their evolution into recognizable cells.This metabolism-first model is not an alternative to life based on RNA. “We can't work without an RNA world either,” says Martin. But it does propose that geology at hydrothermal vents provided the structure in which life emerged, and suggests that understanding prebiotic organic chemistry at these vents may provide the key to understanding the emergence of life from nonlife.While not necessarily convinced of the details of this proposal, Morowitz applauds the focus on bacterial physiology as a guide to understanding early life. “Metabolism recapitulates biogenesis,” he proposes.Chemistry in August 2005, which indicates that single amino acids can catalyze the creation of sugars from simple starting materials with enzyme-like specificity.But for Morowitz, the most exciting development in the metabolism-first camp, “the really new idea,” is that small organic molecules, such as amino acids, can catalyze the formation of other small organic molecules, such as nucleic acids. “This has emerged only in the last two years,” he says. This view has found strong support from a new finding published in the journal “What has emerged is a very strong self-organizing principle,” says Morowitz. In this view, while iron sulfide may have been the original catalyst, it did not remain the only one for long. As products of the original reactions catalyzed new reactions, metabolic networks quickly arose. Feedback loops developed when two molecules regulated one another's synthesis. “The system can piggyback its way upward,” he says.While the study of such networks is still in its infancy, Morowitz suggests they hold the key to a host of knotty problems, including that of RNA synthesis. “It's not a problem in this network point of view. Very early on you get the precursor compounds,” while formation of the complete nucleotide arises later. “Even today this is the core network of biochemistry.”It is still unclear how, or whether, these competing models will fit together, and whether they will lead to a robust scenario for life's origin. Indeed, all may eventually prove wrong, and the real solution may lie hidden in some discovery yet to be made. Whatever the difficulties, says Morowitz, the allure of the field lies in its potential to answer the biggest question of them all. “You're not going to make drugs or better agriculture. You're going to make a philosophical impact.” Szostak agrees: “These are the big questions. Anybody who thinks has to be grabbed by these.”


EHP. The article includes the following caption (p. A 665):I am writing with regard to a misleading photograph and caption in the article “Children’s Centers Study Kids and Chemicals”  publisheMothers, babies, and chemicals. Researchers are studying whether variations in the enzymes that metabolize the phthalates found in some plastic bottles correlate with later birth and growth outcomes.Above the caption is a photograph of a mother-to-be holding a plastic water bottle. Contrary to both the photograph and caption, phthalates are not used in plastic beverage bottles, nor are they used in plastic food wrap, food containers, or any other type of plastic food packaging sold in the United States.The term “phthalates,” short for “orthophthalates,” refers to a class of additives that are used in some plastic products, specifically products made with a particular type of plastic—polyvinyl chloride (PVC or vinyl)—to make the material soft and flexible. Vinyl shower curtains, cable, wire, and flooring are examples of flexible PVC products that can contain phthalates.Plastic beverage bottles sold in the United States are made from a type of plastic known as polyethylene terephthalate (PET). Although polyethylene terephthalate (the plastic) and phthalate (the additive) may have similar names, the substances are chemically dissimilar. PET is not considered an orthophthalate, nor does PET require the use of phthalates or other softening additives.Another article in the same issue, “Are EDCs Blurring Issues of Gender?” , echoes EHP address the misinformation that appeared in these articles and which is available on the EHP website.The American Plastics Council respectfully requests that