MRSA Image via Wikipedia

FORBES.com, October 11, 2010, by Matthew Herper — The little girl had 30 sores on her chest caused by methicillin-resistant staphylococcus aureus bacteria, also know as MRSA.

Pediatrician Jennifer Shu put the child on powerful antibiotics and told the girl’s father to bathe her in diluted bleach and squeeze the pus from the sores. Shu, the medical editor of the American Academy of Pediatrics’ HealthyChildren.org web site, just felt lucky her patient avoided being hospitalized.

Drug resistant bacteria, once confined to hospital wards, are now commonplace in pediatrician’s offices. David Pollock, of the Children’s Hospital of Pennsylvania’s health network, says strains like MRSA have forced him to use potent drugs he would have avoided a decade ago because of their side effects. And what happens when those, too, stop working? “There hasn’t been a new antibiotic developed in kids for 10 years,” he says.

It’s no better for grown-ups. MRSA alone kills 18,650 Americans annually, more than HIV. Yet the field of antibiotic development has been at a standstill for two decades. Now executives, analysts, and researchers see a potential resurgence for bacteria-fighting drugs even as more germs evolve defenses to one or more antibiotics.

The shortage of new bacteria-killers is the result of a “vicious cycle,” says Pedro Lichtinger, a former Pfizer executive who since May has headed antibiotic developer Optimer Pharmaceuticals. The success of previous generations of antibiotics led companies to de-emphasize the drugs. Those firms that pursued germ killers ran into regulatory hurdles that further dissuaded new entrants.

“Resistance to antibiotics doesn’t emerge over a day, a week, or a month,” says Lichtinger. “New products are unattractive financially until the problem is so big. But if you don’t develop the medicines early, people are dying.”

A bacterial skin infection via Wikipedia

Optimer is one of a cadre of antibiotic developers whose drugs are either nearing FDA review or entering the last stages of clinical trials. Its lead drug, fidaxomicin, targets the Clostridium difficile bacteria, which causes 500,000 cases of diarrhea every year and is frequently resistant to first-line drugs. He boasts that 50% fewer patients get the diarrhea again when they are treated with fidaxomicin instead of the current standard, vancomycin. The product could hit the market next year; the investment bank Needham & Co. forecasts worldwide sales of $170 million in 2013.

Will these drugs hit a wall at the FDA, just as their predecessors did? Standards for new antibiotics were already tightening in 2007 when the use of Ketek, a much-hyped antibotic from Aventis, had to be restricted because the pill caused liver damage. Congressional hearings painted Aventis’ studies of Ketek as sloppy, and criticized FDA officials. In 2008, three antibiotics went before an FDA advisory panel, and only one made it. That drug, Vibativ from Theravance and Astellas, has been a commercial disappointment so far, partly because it was not approved for pneumonia, which most experts see as its most obvious niche. Johnson & Johnson abandoned its attempts to get antibiotics developed by partner Basilea. Pfizer stopped work on a drug it acquired as part of its $1.9 billion purchase of Vicuron in 2005.

Acinetobacter baumanii via Wikipedia

The standard-bearer to put an end to this trail of failure is ceftaroline, from Forest Laboratories. On Sept. 8 a panel of advisors voted unanimously that it should be marketed. Analysts at Credit Suisse forecast sales of $138 million in 2015.

“There’s no way that drug is not going to be approved,” says Jeffrey Stein, chief executive of a company called Trius Therapeutics, which is developing its own anti-MRSA drugs.

Another encouraging sign, Stein says, is new guidance from the FDA on how companies should conduct studies of new antibiotics aimed at skin and soft tissue infections, one of the biggest problems caused by MRSA. The last such document came 12 years ago.

FDA scientists delved into clinical trial designs going back to the first antibiotics in the 1930s and 1940s, a time before placebo controls were common, says Ed Cox, the director of the FDA’s division of anti-infective drugs. They found that the best data were not for whether or not drugs cured patients, but for whether they shrank the size of lesions on the skin and stopped fever.

Clostridium difficile via Wikipedia

Cox and his staff swam against the medical mainstream, which in other diseases is pushing for harder measures like cure rates or survival. These will still count, Cox says, but they risk missing subtle differences between drugs. This is especially important because antibiotics must be tested in non-inferiority trials, which aim only to prove that the new drug is as good as old options, not that it’s better. Tiny differences matter.

For Stein the guidance is good news because it matches up well with studies Trius has already started on its lead medicine. Trius’ drug, torezolid, is in the same class as Pfizer’s Zyvox, the last antibiotic to reach $1 billion in annual sales, but with better potency and dosing.

Pseudomonas via Wikipedia

But are draft guidelines really a step forward? The new guidance “goes partway toward solving some problems,” says Alan Carr, the financial analyst who covers antibiotics for Needham. But he cautions thath there are “still gaps” and that the agency often fine-tunes its draft guidance substantially. In other areas, like pneumonia, he sees concern that he guidance will call for clinical trials that will cost as much as hundreds of millions of dollars – matching the peak sales of most antibiotics. That would certainly put a damper on antibiotic development. The FDA’s Cox says he is very concerned that studies not become too expensive.

The FDA is not alone in trying to work out a regulatory framework in which antibiotics can be approved. The Foundation for the National Institutes of Health has been holding meetings to try and help drive consensus of how new antibiotics should be tested, helping to drive the FDA’s decisions.

Finding a way forward is critical, says Ramanan Laxminarayan, senior fellow at Extending the Cure, has spent years pushing for doctors to pay more attention to not overusing the antibiotics we already have. But new drugs are needed if we’re going to keep the bacteria at bay. “If there’s another approach that will deal with these bugs,” says Laxminarayan, “I haven’t heard of it.”

Antibiotic Army

These 13 companies are working on new ways to battle bacteria.

Company How it is fighting the germs
Achaogen This private company is still only in mid-stage trials, but is developing next-generation drugs for gram-negative bacteria, for which there are few treatments.
Advanced Life Sciences ALS is developing oral antibiotic Restanza to treat community acquired pneumonia and inhalation anthrax.
Basilea Spun-out Roche antibiotics division. Lead drug rejected because of problems with clinical trials, and partnership with Johnson & Johnson severed.
Cempra Privately held firm is developing sodium fusidate, which is already used outside the U.S., against MRSA and other bugs.
Cubist Pharmaceuticals Its Cubicin is approaching blockbuster status. Company hoping for next hit.
Durata Team from biotech Vicuron bought stalled antibiotic dalbavancin from Pfizer in hopes they could get it to market.
Forest Laboratories Its ceftaroline passed FDA advisory committee with flying colors in both pneumonia and skin infections
Optimer Pharmaceuticals Its fidaxomicin is targeted against the C. difficile bacteria that causes 500,000 cases of diarrhea in the U.S.
Paratek Pharmaceuticals Developing a new class of antibiotics derived from tetracyclines; partnered with Novartis.
Rib-x Is developing new drugs in the same classes as Cipro and Zyvox.
Tetraphase In the early stages of developing new antibiotics derived from tetracyclines.
Theravance Televancin is approved for skin infections, but not for pneumonia, where potential is greatest because it enters lung tissue.
Trius Therapeutics Searching for heirs to Pfizer’s Zyvox using natural products; in late-stage trials.

Portion-size Illusions

October 11, 2010  —  Be portion-size savvy: Pour a bowl of cereal. Dump into a measuring cup. Compare it to the serving size on the box. Repeat with other food

Most people are not very good at judging how much food is on their plate. We may think we’re eating a normal-size portion when, in reality, we’re putting back two to three times the recommended amount. Do you know how big your portion sizes are? Try this test. Pour yourself your usual serving of cereal. Now empty your bowl into a measuring cup to see how much you’ve got. How does it compare to the serving size on the box? “But cereal portions are tiny!” you’re thinking. If a single-cup serving of cereal won’t fill you up, add two tablespoons of ground flaxseed and half a cup of blueberries. The healthy fat in the flaxseed and the fiber of the blueberries will help fill you up. Plus, you’ll get far more nutrients than eating a bowl of cereal alone.

Paul R. Ehrlich*

Stanford University, Stanford, California, United States of America

Dr. Paul R. Ehrlich

PLoS Biodiversity, The human predicament—climate disruption, loss of biodiversity and ecosystem services, toxification of the planet, the potential impacts of nuclear war, and social and economic inequities that impede solutions to escalating environmental problems—has been amply described [1]. Although the steps needed to solve the predicament are clear, few have been taken—even as the situation steadily declines. The trend in greenhouse gas emissions has continued rapidly upward. The extermination of biodiversity and loss of natural services has proceeded unabated. The number of hungry people has hit an all-time high, which means that so has the number of immune-compromised individuals. That, combined with continued rapid population growth, increases the probabilities of vast epidemics [2]. In Asia, melting of the Himalayan water tower [3] and rising temperatures threaten the food supply of 1.6 billion people [4] whose countries are armed with nuclear weapons [5]. There also have been increasing signs of great toxic peril for humanity and its life-support systems, with a growing threat from the release of hormone-disrupting chemicals that could even be shifting the human sex ratio [6] and reducing sperm counts.

Despite the clear warnings about the predicament almost two decades ago from the scientific community [7],[8], precious little has been done. That’s why a group of social and natural scientists and scholars in the humanities is starting the Millennium Assessment of Human Behavior (MAHB, pronounced “mob”). The admittedly ambitious aim is to change human behavior to avoid a collapse of global civilization.

The urgent need for this call to action is clear when you consider that efforts to address even the most publicized of environmental problems—climate disruption—have fallen far short. Fifteen international conferences have effected no significant change in the accumulation of greenhouse gases and no enforceable agreement yet to reverse the trend. How much failure is enough? Even if nations were to fulfill their recent pledges, catastrophic climate change might well be inevitable [9]. The climate challenge will persist over centuries or even millennia [10] and will require an urgent revision of humanity’s energy mobilizing systems and of deforestation and other greenhouse gas (GHG)-releasing land uses. It will also necessitate a continual reworking of water-handling infrastructure to adjust to changing precipitation patterns that are vital to agriculture, as well as massive adjustments of human settlements as sea levels rise, among many other adaptations.

Whereas at least climate disruption is on the political agenda, most of the other issues are not, and public understanding of what drives environmental deterioration or, indeed, of natural phenomena in general is minimal. Few non-scientists are familiar with the basic idea that environmental damage is a product of population size, per capita consumption, and the sorts of technologies and social and economic systems that supply the consumption. A vast “culture gap” has developed over the past century or so between what our society knows and what each individual knows—a gap that has proven especially troubling when elected officials and other leaders have almost no knowledge of science [11].

That’s one reason why the devastating environmental consequences of an ever-expanding human population have been largely ignored. Governments in many struggling poor countries fail to support family planning programs adequately, whereas those in the rich countries of Europe are irrationally encouraging higher fertility [12]. Few recognize that adding a billion people to the population in the future will cause more damage to humanity’s critical life-support systems than did the most recent increment of a billion, as ever more scarce and remote resources must be tapped to support the newcomers.

Overconsumption by the rich is central to the deterioration of human life-support systems, but is ignored because most business economists, corporate executives, and politicians view it as an unalloyed good. To lead decent lives, at least two billion people are in dire need of more consumption, but extending American consumption patterns to even today’s 6.8 billion people is not only unsustainable but likely a biophysical impossibility.

It would, sadly, take many decades for humane actions to produce significant changes in today’s population trajectory. Yet, we know that consumption patterns can change virtually overnight, as demonstrated by the mobilizations and demobilizations connected with World War II. Enormous changes in production and consumption occurred in the United States in 4–5 years, and, during those years, Americans accepted rationing of gasoline, sugar, and meat. Given appropriate incentives, economies can be transformed extremely rapidly.

Undertaking a World War II–type mobilization, possibly lasting several times longer, to reduce GHG emissions fast and deal with the rest of the predicament would take vast political courage. The urgent need now is clearly not for more natural science (although in many areas it would be helpful) but rather for better understanding of human behaviors and how they can be altered to direct Homo sapiens onto a course toward a sustainable society, to muster that courage before it’s too late. Indeed, the academic focus for solving the predicament needs to shift dramatically to the social sciences and the humanities. Understanding such things as how social norms are generated and how individual actions get translated into group behavior are, in my opinion, central to organizing a successful effort [13].

It is human behavior, toward one another and toward the planet that sustains us all, that requires rapid modification. The MAHB [14],[15] hopes to provide a basic mechanism to achieve this by (1) exposing society to the full range of “inconvenient truths” regarding population–environment–resource–ethics–power issues, (2) sponsoring a broad global discussion involving the greatest possible diversity of people, and (3) trying to close crucial parts of the culture gap.

We must humanely reduce the size of the global population, take steps to stop the growth of per-capita consumption among the rich (while increasing it among the poor), and face the need to gradually reduce the scale of the entire human physical economy. This will require developing mechanisms to force big corporations (including those in big agriculture and big pharma) to bear social responsibilities like the real individuals whose rights they legally want to assume [16]. Corporations are not an essential feature of capitalism, and, in any case, one of the most inconvenient truths is that if capitalism must depend on non-asymptotic perpetual growth of the physical economy, capitalism will disappear. Like it or not, the human enterprise simply must be constrained if it is to persist.

The MAHB intends to generate a global discussion of the human predicament, what people desire, and what goals are possible to achieve in a sustainable society. The MAHB also differs in seeking input from both the scholarly community and the general public on how to organize itself, and it will remain open to such input (see Box 1).

(click to read Box 1)

http://hubs.plos.org/web/biodiversity/article/10.1371/journal.pbio.1000330

I hope that as many readers of PLoS Biology as possible will get engaged in the MAHB, create discussion groups, and communicate with other discussion groups and the general public to jumpstart a global conversation and a mass movement. Those groups are already forming, one even at the middle-school level, and symposia and get-togethers focused on the MAHB are already scheduled for the annual meetings of the Ecological Society of America in Pittsburgh and the World Congress of Sociology in Sweden, both in the summer of 2010.

Within academia, I hope the MAHB can become the focus of badly needed new, coordinated efforts by social scientists and scholars in the humanities to help solve the human predicament. It will seek key points at which human behavior should be changed and evaluate the most humane ways to do it, finding new ones and working with old ones, ranging from Sabido soap operas (e.g., [17]) and proper “framing” of issues [18] to deliberative polling (e.g., [19]).

In relation to both outreach and research functions, the MAHB envisions establishing an “observatory” on behavior, gathering evidence from existing documents, established databases, and global stakeholders, and promoting new directions for outreach and new research projects. If funding can be found, the behavioral observatory would establish a MAHB-line (analogous to Medline), providing access to social science and humanities research relating to sustainability. It will have an interactive portal receiving and providing up-to-date information about particular environmental problems, human factors relating to these problems, and initiatives to deal with them.

The MAHB aims to organize a world megaconference in 2011 or 2012 that would initiate a continuing process, making the MAHB a semi-permanent, autonomous transnational institution. I emphasize “transnational,” as it should focus on relationships of people around the world with one another and their environments, and not “international,” which shifts the focus to between nation states, clearly obsolescent institutional structures. The MAHB is now at a preliminary stage; its nascent website has just been opened to the public. The need for input from people accustomed to working in the social sciences and humanities, in the media, in the business community, and so on, is obvious. If you are willing to get involved, go to http://mahb.stanford.edu/. There, you can join the effort to get humanity to do what is obviously required but usually deemed impractical. A global consensus on the most crucial behavioral issues is unlikely to emerge promptly from the MAHB or any other transnational effort. But, since the MAHB is envisioned as an ongoing flexible effort, not all the goals would need to be reached immediately. If the scientific diagnosis of humanity’s approaching collision with the natural world is accurate (and I and my colleagues believe it is), what alternative is there to trying?

Acknowledgments

This work is dedicated to the memory of Ramon Margalef and based on the Margalef Prize address, Barcelona, November 4, 2009.

Footnotes

The author has declared that no competing interests exist.

References

1. Ehrlich P. R, Ehrlich A. H. The dominant animal: human evolution and the environment (second edition) Washington, DC: Island Press; 2009.

2. Daily G. C, Ehrlich P. R. Impacts of development and global change on the epidemiological environment. Environment and Development Economics. 1996;1:309–344.

3. Xu J, Grumbine R. E, Shrestha A, Eriksson M, Yang X, et al. The melting Himalayas: cascading effects of climate change on water, biodiversity, and livelihoods. Conserv Biol. 2009;23:520–530.

4. Lobell D. D, Field C. B. Global scale climate-crop yield relationships and the impacts of recent warming. Environ Res Lett. 2007;2:014002.

5. Toon O. B, Robock A, Turco R. P, Bardeen C, Oman L, et al. Consequences of regional-scale nuclear conflicts. Science. 2007;315:1224–1225.

6. Howden D. Toxic chemicals blamed for the disappearance of Arctic boys. 2007 September. The Independent. Available: http://www.independent.co.uk/environment/green-living/toxic-chemicals-blamed-for-the-disappearance-of-arctic-boys-402077.html. Accessed 26 February 2010.

7. Union of Concerned Scientists. World scientists’ warning to humanity. Cambridge, , MA: Union of Concerned Scientists; 1993.

8. National Academy of Sciences USA. Population Summit of the World’s Scientific Academies. New Delhi, India: National Academy Press; 1993. A joint statement by fifty-eight of the world’s scientific academies.

9. Eilperin J. New analysis brings dire forecast of 6.3-degree temperature increase. The Washington Post. 2009 September Available: http://www.washingtonpost.com/wp-dyn/content/article/2009/09/24/AR2009092402602.html. Accessed 26 February 2010.

10. Solomon S, Plattner G-K, Knutti R, Friedlingstein P. Irreversible climate change due to carbon dioxide emissions. Proc Natl Acad Sci U S A. 2009;106:1704–1709.

11. Mooney C. Unscientific America: how scientific illiteracy threatens our future. New York,, NY: Basic Books; 2009.

12. Ehrlich P. R, Ehrlich A. H. Enough already. New Sci. 2006;191:46–50.

13. Ehrlich P. R, Levin S. A. The evolution of norms. PLoS Biol. 2005;3(6):e194. doi: 10.1371/journal.pbio.0030194.

14. Ehrlich P. R, Ehrlich A. H. One with Nineveh: politics, consumption, and the human future. Washington, DC: Island Press; 2004. pp. 282–285.

15. Ehrlich P. R, Kennedy D. Millennium assessment of human behavior: a challenge to scientists. Science. 2005;309:562–563.

16. Gibson K. Fictitious persons and real responsibilities. J Bus Ethics. 1995;14:761–767.

17. Singhal A, Sharma D, Papa M. J, Witte K. Air cover and ground mobilization: integrating entertainment-education broadcasts with community listening and service delivery in India. In: Singhal A. , et al., editors. Entertainment-education and Social Change: History, Research, and Practice. Mahwah,, NJ: Lawrence Erlbaum Associates; 2004. pp. 351–376.

18. Lakoff G. Don’t think of an elephant! Know your values and frame the debate. White River Junction,, Vermont: Chelsea Green; 2004.

19. Fishkin J. S. The televised deliberative poll: an experiment in democracy. Ann Am Acad Pol Soc Sci. 1996;546:132–140.


Articles from PLoS Biology are provided here courtesy of

Public Library of Science

About the Author.

Paul Ehrlich is a professor of population studies at Stanford University (http://www.stanford.edu/group/CCB/Staff/Ehrlich.html). The Millennium Assessment of Human Behavior is his latest initiative to educate the public about the threats that uncontrolled human activities pose to the environment. A pioneer in the field of coevolution known for his long-term studies of the structure, dynamics, and genetics of natural butterfly populations, Ehrlich first sounded the alarm about the environmental impacts of overpopulation and resource exploitation in his 1968 book The Population Bomb. He is the recipient of numerous scientific awards, including the 2009 Ramon Margalef Award in Ecology and Environmental Sciences, which honors exceptional lifetime achievements or discoveries.

Paris japonica

GoogleNews.com, October 11, 2010  –  LONDON — Researchers at London’s Kew Gardens say they’ve discovered the longest genome in the world – and that it belongs to a rather ordinary-looking white flower.

The scientists say the Paris japonica has a genetic code 50 times longer than that of a human being and edges out its nearest competitor, the marbled lungfish.

A genome is the full complement of an organism’s DNA, complex molecules that direct the formation and function of all living organisms. Scientist Ilia Leitch said Thursday that the code for Paris japonica is so long that if it were stretched out it would be taller than Big Ben.

Outside researchers caution that micro-organisms known as amoebas might have longer codes still, but say the find illustrates the staggering diversity of genome sizes.

Although not a difficult plant to grow Paris japonica has a behavior all its own and very distinct preferences. If you ignore these then you may get a dormant rhizome that does not die, but does not leaf up. Take some notice and you will be rewarded with a 30cm tall plant. Combine its preferences and you will get an 80cm specimen that will take your breath away! It is the attention to detail that produces those clumps that you see in photographs.

Firstly it is fully cold hardy and indeed likes to be grown cool, not hot. If anyone says otherwise, then I suggest that it is more to explain the loss of a plant, perhaps over winter, or perhaps missing in spring, rather than the first hand observation of a plant killed by cold – that just does not happen.

It likes full or part shade, and humidity, it dislikes dry air and direct sun. It prefers plenty of humus in the soil and an acid to neutral soil. It dislikes limey soils and will not thrive in clay over limestone. It likes water but it dislikes bad drainage or over-dry soils. That behavior all of its own that I mentioned? Well Paris, at the best of times, may not appear above ground in their first two or three years after planting. This is frustrating but it is normal behavior for the genus. In the case of Paris japonica two years is a short wait, three or even four might be normal, yes really. During this time the plant puts down its few, thick, brittle roots, and until it has roots to take up water, it will not make leaves or flowers to lose water!

During the settling in period each well-meaning poke, or lifting for examination, will break the roots or root initials, and set the plant back even further. Lifting it to check can only damage the plant, the roots and the new shoots. We call this ‘finger blight’ in the office and it is the main cause of problems.

Paris japonica is a plant for the very patient gardener, with faith. It is at the opposite end of the spectrum to bedding annuals, it is not instant, nor even quick, but very very slow. Put it in the ground, about 5-10cm deep. It may not have a well-developed shoot on receipt but if it does, and if this is long, keep the rhizome at the depth advised with the shoot showing above the soil surface. It is best in a damp, well-drained, humus-rich soil in light shade. Never, ever pot it, not even in its first season just to make sure (second only to finger blight in gardener-related problems) then leave it alone, don’t lift it to check and in time you will be rewarded with a gorgeous plant.

Bear in mind also that any, detailed, cultural advice makes a plant sound harder than it really is.