New Geography

Author: Greg Critser

  • A Pill For Los Angeles? Medicating the Megacities

    Los Angeles — and other modern megacities — conjure increasingly unique genetic profiles that point the way to a new medical industry: Call it urbo-pharmaceuticals. Investors are needed.

    Is there a pill that might inoculate us from smog?
    Is there a gene we can target that would make us resistant to resurgent infectious diseases?
    And is there a way to use genetic data to insulate new immigrants from some of the metabolic challenges of living in a new land of plenty?

    Welcome to the slowly emerging world of environmental medicine and its inevitable outgrowth, environmental pharmaceuticals: compounds specifically suited for mitigating the physiological challenges of mega-city life in the 21st century.

    The inchoate drive for such pills — disparate, proceeding in entrepreneurial fits and starts — is fueled by twin facts.

    First: Inflammation, the chronic-over-firing of the body’s immune system, now sits at the core of almost all scientific discussion of chronic diseases, diseases that persist despite thirty years of lifestyle advice, medication and surgical intervention.

    Second: Urban environments today are physiologically inflammatory beyond belief, their brew of fumes, crowding, germs and bad food wreaking all kinds of internal damage and prompting no end of lifelong medical problems. As Dr Marc Reidl, a specialist in respiratory disease at UCLA puts it, “Mega city life is an unprecedented insult to the immune system.”

    The consequent diseases — asthma and COPD, heart disease, diabetes, alcohol and drug addiction — are costly and life-sapping. They are accentuated by the huge inflows of young populations, many from poor rural environments, from Mexico to the Middle East. These new migrants bring their own unique pathogens, and their own unique vulnerabilities. Poverty fuels excess consumption of cheap fruits and sugars, pushes people into smog-proximate neighborhoods and pest-filled homes, and drives them to unhealthful behaviors. And certain genes — most notably the well-studied “hungry gene” — exacerbate the reaction. Consider:

    Asthma and COPD, considered among the world’s top medical concerns, seem to be activated by special sets of genes, some of which accentuate the impact of smog (along with tobacco smoke, the principle culprit in the industrialized world). Other genetic profiles seem to mitigate it. Researchers at the University of Southern California have identified both versions.

    In the Latino population, mutations in liver genes, particularly one well-known one named CYP450, seem not only to fuel alcohol abuse, but also to accentuate some of its gravest consequences: fatty liver disease and cirrhosis.

    Heart disease, as well as problem pregnancies, uncontrolled diabetes, and even sleep apnea, are increasingly driven not just by the traditional devils of unhealthy lifestyle and poverty, but by genes activated by uniquely urban pathogens and concentrated diesel and auto exhaust.

    Genes governing stress responses may be at the root of why traditional antibiotics do not work within the germy reality of big cities. For years, speaking the words “genes,” “immigrants,” and “public health” was the proverbial ticket to a social and political nether-land. It was almost as bad as talking about obesity. It is still a messy brew.

    Yet outside of “nannyism” (not necessarily such a bad thing), or trying to scare away any new migrants (which is), what can be done? One tack might be to take a cue from modern pharmacology’s attempt to develop a pill for Metabolic Syndrome, the debilitating mix of diabetes, high blood pressure and high cholesterol now prevalent in most developed nations. Can we design an urban poly-pill, one built specifically for the inflammatory storms of the mega-city? And can we point it at what might be called the big three: the impairment of respiration, metabolism and cardio vascular processes?

    UCLA’s Riedl, a specialist in respiratory disease, has zeroed in on oxidative stress — the damage caused by unstable, burned-up nutrient particles in the blood stream. He knew that anti-oxidant supplement regimes have been an overwhelming bust, most of them weak and not very good at targeting the body’s native anti-oxidant systems. Then came a number of insights made possible by genetics. Perhaps the most important was a molecule dubbed GSTM1. It is deeply implicated in fighting oxidative stress from smog and other pollutants. Riedl traced the pathway upstream and found that it was driven by another gene product called Nrf-2.

    Then he decided to pharmaceuticalize one molecule derived from broccoli sprouts, sulphoraphane, crafting a concoction using concentrates of the vegetable mixed with daikon root essence. The result was a compound he could try out in various concentrations in humans, then measure whether its effect on Nrf-2 were, in the lexicon of pharmaceutical development, “dose dependent.” It was. The next step will be to test how well it works in people exposed to constant high levels of smog.

    Though the path to any therapy remains long and arduous, Riedl holds a picture in his mind of one possible future. “The Holy Grail for us is if we could identify the population sub group that is most likely to have the mutation that impairs Nrf-2, and who are environmentally vulnerable —say, people who live close to freeways — and essentially do targeted chemotherapy for environmental insults.”

    Among urban woes, metabolic disorders are particularly troublesome. The NIH has singled out type 2 diabetes and fatty liver disease as the two biggest factors driving hospitalization, amputations and prescription drug use. Their effect on health care expenditure is huge and growing. Treatment — let alone prevention — has proved vexing.

    Two promising compounds are under serious study. The first is the grape skin compound known as Resveratrol. Though mainly known for its claim to extend mammalian lifespan, its true value is quietly emerging in diabetes treatment, where early clinical trials showed promising results but, unfortunately, several safety issues.

    And Metformin, a diabetes drug originally synthesized from the French lilac plant, may have huge protective benefits for urbanites. Researchers at UCLA Riverside have used microchip arrays to discover that it activates liver genes that dampen high insulin levels and vascular inflammation.

    At USC, one of the world’s leading centers for studying diabetes and liver diseases, scholars have pinpointed a gene that, when activated, causes fatty liver disease, another potential urbo-drug target. As Michael Goran, the head of USC’s diabetes research, notes: “In Mexican Americans there is mutation in a gene called PNPLA1 which is related to an elevation in liver fat which could be related to increased diabetes risk and definitely [is] related to longer term increase in liver disease; this mutation is highly prevalent in Hispanics/Mexican Americans; moreover, in our own research we have just discovered that: a) the effect of this gene is manifested very early in life and b) the effect of this gene on increasing liver fat is promoted by high sugar intake.”

    What about the heart? UCLA heart researcher Alan Fogelman, the dean of modern HDL research, has two compounds in small clinical trials that would help the body restore its ability to make good cholesterol, a process increasingly undermined by the smog, virii and bad food of mega-cities. Both are peptides — short, protein-like molecules — that target specific gene products activated by chronic inflammation, which can include everything from the flu to sleep apnea to unchecked diabetes. The compounds are being developed by Bruin Pharma, a commercial venture in which Fogelman is a principal and an officer.

    What are his HDL peptide’s chances? “It is so early to try to tell something like that,” he says. “We have no idea where that effort will take us, or whether it will hit the target we hope. We have to wait for the trials.”

    Yet waiting, especially when it requires patience and foresightedness, is something we as a society seem incapable of, especially when dealing with complicated public health issues. But what if there were a faster, cheaper way? Urbo-pharmaceuticals might be one ticket. After all, we are patient and forgiving when it comes to pills and the time, cost and uncertainty that comes with their development.

    Chalk that up to the ease-seeking nature of humans, something for which there is no pill, but which, in itself, might drive us to invest in a poly pill for modern life.

    Greg Critser’s new book is Eternity Soup: Inside the Quest to End Aging (Random/Harmony 2010).

    Photo by ilmungo / Luigi Anzivino, Los Angeles from the top of Temescal Canyon Trail, “…taken not at sunset, but at 11AM… that pretty peach-colored layer in the sky is the famous LA smog.”

  • The Gero-Economy Revs Up

    Green jobs? Great. Gray jobs? Maybe an even better bet for the new jobs bill. If there is a single graphic that everyone concerned with the nation’s future should have tattooed on their eyeballs, my vote goes to the one on your left. Here is its central message:

    Forty years from now, one out of four Americans will be 65 or older.

    Twenty million will be over 85.

    One million will be over 100.

    So far the Big Think on such numbers might be boiled down to a few reasonable conclusions: People will have to work longer and delay retirement. The government should underwrite serial job retraining and promote new kinds of annuity plans. These will boost tax revenue that would help pay the nation’s growing Social Security and Medicare tab. “[It] would constitute a kind of neo-welfare state—a new covenant—that promotes individual responsibility in alliance with the voluntary sector, the market, and government,” observes Robert Butler, the dean of modern gerontology. He calls his package “productive aging.”

    But there is a third rung: incentives to make aging an engine of economic growth. There’s gelt in that there gray! It’s the entire world that’s aging, after all, and that world’s in need of gero-tools, gero-think, gero-innovation. We’ve got it. Let’s sell it – to China, Europe, India.

    I spent some time recently with innovators in this realm. Perhaps the most exciting were those designing new-style senior housing—ranging from high end architects and builders to small time real estate entrepreneurs. They are pursuing ways for the elderly to live more comfortably and safely in their own homes and communities.

    In Palo Alto, one former real estate saleswoman, frustrated with the elder-scary housing stock in that uptown realm, took to providing what turned out to be a popular and profitable service: gero-fitting, or “prostheticizing,” those ultra-modern (and hard-edged) homes with senior-friendly accoutrements: hand bars everywhere in case of a fall, showers and water sources that adjust heat and flow automatically, wheel chair turns in halls and room-by-room phones and computer screens that activate by voice.

    Nursing homes – places where one normally sees neither – are also slowly emerging out from under decades of under-investment and institution-think. Architects and developers from Sweden (one of the fastest aging nations in the world), Japan (the fastest in Asia) and even Italy (one of the most unprepared gero-nations) have been retooling the unfulfilled promise of universal design to come up with new construction methods and new construction materials.

    Yet it’s American builders, with their vast experience and regional flexibility, who stand to be generational leaders in the most profitable arena: building new homes. Where are they?

    Then there is transportation. Cars–and our addiction to them–are perennially painted as villains in elder-world. Yet until they are in their early 80s, aged drivers far outperform their younger counterparts, with fewer injury accidents and fewer tickets. Nevertheless, finding ways to make driving safer and more comfortable suggests another major opportunity: prostheticizing the automobile and making highways less cognitively confusing.

    Here in Los Angeles, the original car capital, one company is using space program sensor technologies to make cars that warn drivers when they are tailgating, when they are weaving, when their off ramp is coming up. Roadways? Someone needs to use our state-of-the-art understanding of cognition to redesign everything from highway signs to lighting. A few farsighted firms are already trying to do so. We need more.

    The aging of the modern stomach could also drive food science to develop new staples that are less glycemic (high blood sugar being one of the biggest sources of chronic inflammation in the elderly) but still tasty and satisfying. And, instead of being peremptorily dismissed, the “anti-aging” medical movement could be scientifically (and systematically) plumbed for real medical advances, tested with gold standard clinical trials, and then sold to the rest of the arthritic world.

    Who, then, will lead? Who will become the Bill Gates of ElderWare, the Al Gore of GeroWarming, the Warren Buffett of AlterAssets?. Right now, we’re still waiting.

    “The boomers are going to have a rougher time in retirement than their parents,” says Robert Butler. “That can mean two things: they can complain about it, or they can retool it for their kids and take advantage of its promise.”

    Greg Critser’s new book is Eternity Soup: Inside the Quest to End Aging (Random/Harmony 2010).

  • City Planning and The Politics of Pollution

    Part Two. Yesterday, in Part One, Critser discussed scientific advances in understanding air pollution. Today, he addresses the social implications.

    The new science of air pollution, with its emphasis on dose-response mechanisms, may remake the traditional advocacy realm of social and environmental justice. In the past, that world has been focused on class, race and ethnicity, classic markers of inequality and vulnerability. Today, the focus is more “exposure driven.” “Dosage… may be something people who have ignored environmental justice can get their heads around,” one researcher at last month’s Environmental Epidemiology conference in Pasadena noted. “It may get people’s attention on something that affects us all.”

    Other new observations are recasting ancient (and highly suspect) urban-suburban dichotomies as well. If one parses the science of small, regional temperature increases—the kind we may see more of in the future—and how those spikes “activate” ultrafine particles, one discovers a disturbing phenomenon: The combination of heat and UFPs makes airborne plant pollens more inflammatory. Such was the finding of Italian researchers studying how traffic emissions and high temperatures in Naples fortify the toxicity of urtica, the common allergen known as the nettle plant. One wonders how the same combination remakes the lovely sage and chaparral environment surrounding Southern California suburbs, even when the region isn’t burning. It is a disturbing prospect for those who believe they have escaped inflammation by exchanging big cities for exurban greenlands.

    What, besides moving to Iceland, can be done? Few have thought more about that, at the practical level, than Andrea Hricko, an associate professor of clinical preventive medicine at USC, where she is trying to translate epidemiological data about pollution into practical public health policy. For years, Hricko’s focus was the Port of Los Angeles and the neighborhoods and schools surrounding that diesel-saturated realm. What she found were huge spikes in childhood chronic diseases, especially asthma, as well as other heart and lung problems. She and others succeeded in getting one school relocated—pushed back from the most truck-intensive route near the Alameda Corridor—but even that victory was a lesson in the unintended consequences of regulation.

    “Come over here, you have to see this,” she said to a visitor one day in her crammed office on the medical school campus. On her computer appeared a picture of a group of kids playing soccer. In the immediate background loomed trucks belching the substances that eventually make the port air so heinously foggy. “See, this is where the school was. This was supposed to be the buffer zone, but… being that it is also rare, unoccupied space, and LA schools have so little recreational area, it is now a defacto playground. So you have kids better protected inside, but doing their deepest breathing part of their day right on top of the trucks.” It’s a perfect public health storm, she notes, because “getting kids outside and exercising more is a huge priority in the obesity-diabetes crisis.”

    Hricko’s focus on the ports, arguably the octopus of contemporary industrial Los Angeles, has taught her some hard lessons. You can always get a regulation that says, for example, don’t build a school within X distance of a freeway, but you can rarely switch the scenario around, say, with a ruling that says don’t widen a freeway when it is within X distance of a school. The same is true of building a new rail yard, as is the case just north of the port today. For years, area residents waged war with the railroad and the port to simply locate the new yard closer to the water, which would have drastically reduced the number of short, emission-intensive trips by trucks, and thus hopefully cut down the high rate of respiratory disease in the area. The solution, instead, was to go ahead and build the yard right by the homes, with a promise by state regulatory agencies to install new, high efficiency filters in all area homes. While that protects the children while they’re inside—and, it would seem, suggests a possible boom enterprise for the filter industry—it’s far from an ideal solution. “They’re still spending most of their time outside, and we still need to get them to exercise more while they’re out there. It’s a frustrating exercise.”

    Hricko has also wondered if the same impasse won’t obtain in the arena of the low-income housing juggernaut led by Los Angeles Mayor Antonio Villaraigosa. One recent hearing concerned an affordable housing complex proposed alongside the 5 freeway near East Los Angeles. As Hricko tells it, that project would be sandwiched between one of the most emissions-choked portions of the freeway and the mass transit Gold Line, which would run just behind it. “There was all kinds of talk about filtering, etcetera, but the real question was never brought to the fore: Perhaps this shouldn’t be considered for housing in the first place.” She notes that a member of the LA County Public Health staff made precisely this point… privately.

    One can understand why. Affordable housing is an important, unmet need in Los Angeles, one with a substantial political establishment behind it and a charismatic mayor in front of it. There is, as a result, an understandable reluctance to get in the way of the parade, especially after years of political impasse. The mayor recently upped the ante and proclaimed a new $5 billion housing initiative, much of which would center on building new housing near mass transit stations. The essence of this transit pod strategy has a fairly sustainable logic: If you can get people to live near mass transit, you’ll dramatically reduce one of the biggest single factors in urban pollution: the numerous short, one-to-five mile trips that people make every day, whether to work or to the store or to pick up the kids at school. You’ll also reduce traffic jams.

    The problem, of course, is human nature, and the naughty desire by poor people, especially in Los Angeles, to be like the rich people, driving whenever and to wherever they want. Compounding this, for the scheme to work, we still must get from the station to work and people will use a car to do that. “For Antonio’s plan to work, you’d basically have to make it a condition of ownership that you don’t have a car. Or, that if you are going to buy this housing, you have to work somewhere on the trainline,” Hricko said with a knowing smile. “Because if you don’t, you still have people driving. You’re defeating your purpose before you ever get started.”

    That’s one realm where a leader like Villaraigosa, with his celebrity status and megawatt smile, could lead by example. But that hasn’t happened so far. Mike Woo, who describes himself as a supporter of the mayor, says “I want to say that I think the mayor’s people are on top of this. I wish I could say that. I really wish I could say that.” Woo notes that there is a slightly bigger time window for solving the housing crunch than is popularly acknowledged. The Planning Commission’s most recent staff report holds that meeting the need for housing in most transit corridors for the next 8-10 years does not require raising the density of housing.

    That’s a rare breather, Woo says. Let’s make the most of it.

    Greg Critser is the author of Fat Land: How Americans Became the Fattest People in the World (Houghton Mifflin 2003), Generation Rx: How Prescription Drugs Are Altering American Lives, Minds, and Bodies (Houghton 2005), and Eternity Soup: Inside the Quest to End Aging (Random/Harmony 2009).

  • Will The New Air Pollution Science Choke City Planners?

    Part One of A Two-Part Series

    Not long ago, Michael Woo, a former Los Angeles city councilman and current member of the Los Angeles City Planning Commission, took up a case pending approval by that body: a mixed housing-retail development near the intersection of Cahuenga Boulevard and Riverside Drive. Like many of the remaining buildable sites in the city, the property is right next to a roaring motorway; the windows of some apartments would look right out onto the 134 Freeway. To Angelinos, who have grown up in a car culture, it was hardly a remarkable proposal. But Woo, perhaps one of the brainier members of the city’s political elite—after losing a mayoral race to Richard Riordan in the early 1990s he became a professor of public policy at University of Southern California—had a problem with it, and he couldn’t quite let it go.

    Just a few weeks before, the Commission had witnessed a lengthy presentation by a scientist who’d been studying how living within 500 yards of high traffic corridors—freeways and some particularly busy streets—substantially raises the risk for a number of chronic diseases. “We were all sort of sitting there, looking at this proposal and discussing it through the conventional lens we normally use, when I said, `Wait a minute. Didn’t we just hear a pretty compelling argument about this the other day? Can we talk about that for a minute?’ It struck me that it was impossible to read those studies and then continue approving housing that sits that close to freeways.”

    The Commission then asked for the developer’s point of view on the issue. “As I recall, the only real mitigation that they brought up was almost comic,” Woo says. “Their idea was, you know, we’ve got that covered: We’re going to make sure that residents can’t open the windows that face the freeway.” The project was approved.

    Woo doesn’t particularly fault anyone in the exchange, because the implications of the new science of air pollution—much of it driven by pioneering work at USC, the University of California at Los Angeles, and California Institute of Technology—are utterly mind boggling. No one has quite calculated exactly how much buildable land would be excised from use for housing and schools if this growing body of work were to take hold in the policy realm, but, as Woo said, “We can’t hide from this issue anymore. The hard science on the subject is compelling. It makes you fundamentally rethink some pretty key parts of how, where and why we’re building housing in such locations.”

    For decades, pretty much everyone “knew” that smog—usually measured as ozone, the gas that forms from sunlight’s ionizing effect on air particles—caused all kinds of health problems, principally those associated with the lungs, like asthma. But the truth of the matter is that, until ten years or so ago, no one knew how that happened; they didn’t know the “mechanism of action,” the intricate physiological processes that lead to chronic airway inflammation. Epidemiological data was confounding, because some high ozone communities showed lower rates of asthma than low ozone communities. Also, smog levels—measured as ozone—were going down, while asthma rates were going though the roof.

    One suspect was what researchers called fresh emissions, comprised of ultrafine particles, or UFPs, which are so small that they can penetrate the furthest reaches of the lung’s bronchial branches and set off the systemic inflammation that causes respiratory disease. Thus, it was possible to have lower ozone levels and still have increased levels of inflammation, or as USC Professor Robert McConnell notes, “You could have cleaner horizons but still have increasing inflammation to people who live closer to where the particles are being produced.” McConnell has been leading the federally funded Children’s Health Study in Los Angeles for over a decade. “I tell people that I’m studying how pollution causes asthma, and people look at me and say, `I thought we already knew that,’” says McConnell. “The fact is that we assume risks that aren’t there, and we’re ignorant of risks that are there.”

    What caused the sea change in pollution epidemiology—the ability to link exposure to tail pipe emissions and chronic diseases—is as much a story of ingenuity at the lab bench as it is one of persistence against conveniently indolent regulations. At USC, engineers over the past 20 years have invented ways to concentrate particles from the freeway, assess their specific toxicity in human doses, and then test various theses with lab animals genetically engineered to physiologically respond like humans. They have also developed ways to track real-time daily human exposures to ultrafine particles. On any given day in Los Angeles there are mobile smog units measuring how pollution ebbs and flows on a neighborhood-by-neighborhood basis. There are people wearing “personal ambient pollution” backpacks to track how individuals experience different loads of smog throughout their day, part of which may be spent in a low-pollution environment, part in a high. Through modern genomics, we also now know that several highly prevalent gene mutations make some people more susceptible to pollution, and that others make them less susceptible.

    At all three universities, engineers in the aerosol sciences developed machines that could accurately measure not just ozone—a rather crude measure of air toxicity—but also specific toxins, known as ultrafine particulate matter, or UFPs, of less than 2.5 microns. It is stuff so small that it can reach the bottom of the airways; there, it can over-stimulate the so-called inflammatory cascade of the body’s native defense system and turn it into a disease called asthma. At UCLA, cell biologists, toxicologists and lung and heart specialists have even been able to image what happens to the human cell when it’s exposed to high levels of ultrafine particles. It is the kind of image that can make one utterly despairing, but one that also might clue modern physicians, medical researchers and environmental scientists on how to better focus on the issue and perhaps mitigate it.

    A few examples of new directions within the science:

    Ultrafine Particles, Diesel Exhaust And Asthma: A growing consensus holds that, infants, young children, and expectant women experience substantial elevations in risk for deficits in lung function growth when living near high volume motorways. There is less consensus on the recommended buffer zone, ranging from 75 meters to 500 meters.

    Ultrafine Particles And Heart Disease: A growing body of laboratory experiments and human observational work links heart disease, especially the process leading to atherosclerosis and heart attack, to air pollution. Recent work at UCLA and USC on lab mice parked next to the 110 Freeway has suggested an alarming thesis of causality: That chronic exposure to high levels of ultrafine particles may make us more likely to get heart disease because it makes HDL—the so-called “good,” form of cholesterol that “cleans up” the bad form—dysfunctional.

    Diesel, Ultrafine Particles And Alzheimer’s: Work coming out of Mexico City, increasingly LA’s sister city in the environmental sciences, documents how amyloid plaque, one of two suspect brain proteins associated with Alzheimer’s, increases with exposure to air particles, especially in children and young adults.

    Diabetes, High Blood Pressure And Obesity: A small but growing body of research shows that being fat and breathing smog is really bad for you. Worse, high exposures may accentuate existing diabetes and metabolic syndrome, the perfect storm of high cholesterol, high blood sugar, and high blood pressure.

    Air Pollution, Expectant Mothers, And Infants: UCLA researchers have repeatedly demonstrated a consistent, dose-dependent relationship between expectant mothers living in high traffic-emission-adjacent housing and premature births, low birth weights, birth defects and respiratory diseases. In a recent report, the UCLA Institute of the Environment concluded that the problems were of such magnitude as to “require drastic changes to motor vehicle and transportation systems” over the next decades.

    In Part Two, Critser explores the politics of pollution.

    Greg Critser is the author of Fat Land: How Americans Became the Fattest People in the World (Houghton Mifflin 2003), Generation Rx: How Prescription Drugs Are Altering American Lives, Minds, and Bodies (Houghton 2005), and Eternity Soup: Inside the Quest to End Aging (Random/Harmony 2009).

  • Greg Critser