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Thursday, October 4th, 2012

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    4:00a
    The mathematics of leaf decay
    The colorful leaves piling up in your backyard this fall can be thought of as natural stores of carbon. In the springtime, leaves soak up carbon dioxide from the atmosphere, converting the gas into organic carbon compounds. Come autumn, trees shed their leaves, leaving them to decompose in the soil as they are eaten by microbes.  Over time, decaying leaves release carbon back into the atmosphere as carbon dioxide.

    In fact, the natural decay of organic carbon contributes more than 90 percent of the yearly carbon dioxide released into Earth’s atmosphere and oceans. Understanding the rate at which leaves decay can help scientists predict this global flux of carbon dioxide, and develop better models for climate change. But this is a thorny problem: A single leaf may undergo different rates of decay depending on a number of variables: local climate, soil, microbes and a leaf’s composition. Differentiating the decay rates among various species, let alone forests, is a monumental task.

    Instead, MIT researchers have analyzed data from a variety of forests and ecosystems across North America, and discovered general trends in decay rates among all leaves. The scientists devised a mathematical procedure to transform observations of decay into distributions of rates. They found that the shape of the resulting curve is independent of climate, location and leaf composition. However, the details of that shape — the range of rates that it spans, and the mean rate — vary with climatic conditions and plant composition. In general, the scientists found that plant composition determines the range of rates, and that as temperatures increase, all plant matter decays faster.

    “There is a debate in the literature: If the climate warms, do all rates become faster by the same factor, or will some become much faster while some are not affected?” says Daniel Rothman, a co-founder of MIT’s Lorenz Center, and professor of geophysics in the Department of Earth, Atmospheric and Planetary Sciences. “The conclusion is that all rates scale uniformly as the temperature increases.”

    Rothman and co-author David Forney, a PhD graduate in the Department of Mechanical Engineering, have published the results of their study, based largely on Forney’s PhD thesis, in the Journal of the Royal Society Interface.

    Litter delivery

    The team obtained data from an independent 10-year analysis of North American forests called the Long-term Intersite Decomposition Experiment Team (LIDET) study. For this study, researchers collected leaf litter — including grass, roots, leaves and needles — from 27 locations throughout North and Central America, ranging from Alaskan tundra to Panamanian rainforests.

    The LIDET researchers separated and weighed each litter type, and identified litter composition and nutrient content. They then stored the samples in porous bags and buried the bags, each filled with a different litter type, in each of the 27 geographic locations; the samples were then dug up annually and reweighed. The data collected represented the mass of litter, of different composition, remaining over time in different environments.

    Forney and Rothman accessed the LIDET study’s publicly available data online, and analyzed each dataset: the litter originating at one location, subsequently divided and distributed at 27 different locations, and weighed over 10 years.

    The team developed a mathematical model to convert each dataset’s hundreds of mass measurements into rates of decay — a “numerically delicate” task, Rothman says. They then plotted the converted data points on a graph, yielding a surprising result: The distribution of decay rates for each dataset looked roughly the same, forming a bell curve when plotted as a function of the order of magnitude of the rates — a surprisingly tidy pattern, given the complexity of parameters affecting decay rates.

    “Not only are there different environments like grasslands and tundra and rainforest, there are different environments at the microscale too,” Forney says. “Each plant is made up of different tissues … and these all have different degradation pathways. So there’s heterogeneity at many different scales … and we’re trying to figure out if there’s some sort of commonality.”

    Common curves

    Going a step further, Forney and Rothman looked for parameters that affect leaf decay rates. While each dataset resembled a bell curve, there were slight variations among them. For example, some curves had higher peaks, while others were flatter; some curves shifted to the left of a graph, while others lay more to the right. The team looked for explanations for these slight variations, and discovered the two parameters that most affected the details of a dataset’s curve: climate and leaf composition.

    In general, the researchers observed, warmer climates tended to speed the decay of all plants, whereas colder climates slowed plant decay uniformly. The implication is that as temperatures increase, all plant matter, regardless of composition, will decay more quickly, with the same relative speedup in rate.

    The team also found that plant matter such as needles that contain more lignin — a sturdy building block — have a smaller range of decay rates than leafier plants that contain less lignin and more nutrients that attract microbes. “This is an interesting ecological finding,” Forney says. “Lignin tends to shield organic compounds, which may otherwise degrade at a faster rate.”

    Mark Harmon, principal investigator for the LIDET study and a professor of forest science at Oregon State University, says the team’s results add evidence to a long-held debate over rising temperature’s effect on organic decay: As temperatures rise, decomposition will likely speed up, releasing more carbon dioxide into the atmosphere, which in turn creates warmer temperatures, further speeding decay in a positive feedback loop.

    “There is a wide range of results on temperature response,” says Harmon, who was not involved in the study. “Some have proposed that materials that are hard to decompose will respond more to temperature increases, and others have proposed the opposite. The current study indicates they may be the same,” meaning the positive feedback from rising temperatures may not be as strong as others have predicted.

    Rothman adds that in the future, the team may use the model to predict the turnover times of various ecosystems — a finding that may improve climate change models, and help scientists understand the flux of carbon dioxide around the globe.

    “It’s a really messy problem,” Rothman says. “It’s as messy as the pile of leaves in your backyard. You would think that each pile of leaves is different, depending on which tree it’s from, where the pile is in your backyard and what the climate is like. What we’re showing is that there’s a mathematical sense in which all of these piles of leaves behave in the same way.”
    4:00a
    How better financing could help create new cancer drugs
    The pharmaceuticals industry presents a quandary for potential investors: Major investments in drug development pay off handsomely in a relatively small number of cases, but many other projects deliver no returns at all. The evident difficulty of picking winners can deter investors from putting money into individual companies.

    But a novel way of financing the industry could help bring infusions of money into the drug-development pipelines of many firms, as scholars from the MIT Sloan School of Management outline in a paper appearing this week in Nature Biotechnology. The authors suggest that a large “megafund,” consisting in large part of long-term bonds issued by drug companies, would help fund languishing projects while providing a safer investment option for large institutional investors and money managers.

    “This kind of financing vehicle could actually be a great mechanism to spur the industry to fill those pipelines,” says co-author Andrew Lo, the Charles E. and Susan T. Harris Professor of Finance at MIT Sloan and director of the school’s Laboratory for Financial Engineering.

    Many biotech companies finance their research through venture capital funds when in the startup phase, or by going public and issuing stock as they get bigger. But a new financing arrangement incorporating bonds — also known colloquially as securitized debt — would help mitigate the hit-or-miss nature of drug development for both companies and wary investors, Lo believes. For biotech firms, he says, “using debt financing on a relatively large scale” would bring in more funding, thus “enabling [firms] to support very risky kinds of research projects that currently [they] really can’t afford to take on.”

    From the investment side of things, Lo adds, the paper shows that debt financing produces “relatively reasonable probabilities of default such that the debt can be rated and that you can make a credible case that you could market these instruments to institutional investors.”

    Beyond the valley of death

    The MIT research uses cancer drug research and development between 1990 and 2011 as a model for the wider industry. After crunching numbers on biotech investments, revenues and production patterns for oncology drugs, Lo and his co-authors found that a megafund between $5 billion and $15 billion in size could yield average annual returns from roughly 9 to 11 percent for the equity portion of the fund, and 5 to 8 percent for the debt portion of the fund.   

    “We basically tried to put together a simulation that an investor might want to see in order to gauge the risk and reward for investing in these drugs,” Lo says.

    The key to those returns, the paper emphasizes, is that a megafund would constitute a long-term investment in biotech, in contrast to stockholders who may expect increasing quarterly earnings. The funding vehicle would be aimed at riding out the ups and down of particular firms and drugs, and producing solid returns over many years.

    On the industry side, the megafund concept helps address the problem people in many industrial sectors call the “valley of death” — that is, the challenge of taking promising lab research and developing it into viable products. In 2010, the authors note, the biotech industry spent about $48 billion on basic research, and $127 billion on clinical development, but only about $6 billion to $7 billion on so-called “translational” efforts to transform lab research into drugs that enter clinical trials.

    “There’s plenty of money for basic research, there’s plenty of money for Phase III clinical trials,” Lo says. “There’s not a lot of money for the process in between, and that’s what we’re hoping to support.”

    In addition to Lo, the authors of the paper are Jose-Maria Fernandez, a researcher at MIT Sloan’s Laboratory for Financial Engineering, and Roger Stein, a research affiliate at MIT Sloan and managing director for research and academic relations at Moody’s Corp.

    Evolving finance for an evolving industry

    The impetus for the paper, Lo says, came in part from recent personal experience: His mother died of cancer last year, and Charles Harris, who funded his professorship, died of cancer two years ago. Working on new ways of financing is, in part, Lo’s “way of coping” with the fact that “you feel helpless when your friends and family are stricken with cancer.”

    The megafund idea, as the authors note, faces several hurdles that would need to be addressed, from effective management of the funds to “proper controls” in the regulatory arena, especially surrounding the sale of prospective biotech securities. Still, the paper has received a positive reaction from executives in the biotech industry.

    “I’m excited about it,” says Monique Mansoura, a biotechnology executive and former planning officer at the National Institutes of Health, who has read the paper. (Mansoura was also a part of the MIT Sloan Fellows Program in Innovation and Global Leadership last year.)

    In the paper, the researchers test their financing concept against both the “blockbuster” model of drug production in the industry — in which a small number of products succeed, generating giant returns — and a nonblockbuster version in which more drugs pay off, but are tailored to reach smaller populations of consumers.   

    Mansoura says she found the scenario in which the industry moves away from the blockbuster model to be more compelling. “The idea of a blockbuster [industry] is evolving,” Mansoura says, adding that “the science is pointing toward more stratified, personalized medicine” in the future.

    For his part, Lo says that input of that nature, from industry experts, is essential to help make the megafund concept viable.

    “We’re not experts in oncology or biomedical research,” he acknowledges. “We’re hoping this is going to be the beginning of a much longer and deeper conversation between financial experts and biomedical researchers.”

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