April 2006 Archives

Malaria Treatment, Bioengineering Progress

Humans are sometimes challenged by the tiniest things. Malaria for instance. We continue to fail to control the spread of malaria carried by Plasmodium falciparum, the parasite responsible for the most deadly malaria disease in humans. Although the actual numbers of people who fall ill or die from malaris are difficult to establish because so many cases go unreported, estimates are 515 million cases yearly, and one to two millions deaths. Disease, death, and significant economic repercussions because mosquitoes that weigh a measly 2.5 mg carry the protist in its sporozoite form until it reaches blood via a bite from the female insect. The parasite completes its lifecycle, invading the hepatocytes of the liver and the red blood cells and causing disease and/or death in its human host.

Acronym Required previously wrote about the challenge of malaria prevention and treatment in Malaria Prevention, Progress in Fits and Spurts. At the time, in 2005, Novartis had just announced that it was again unable to produce the quantities of the drug that it had agreed to in its "private-public partnership" with the World Health Organization. Novartis is the sole manufacturer of the drug Coartem, an artemisin based combination therapy that is the most effective treatment for malaria. In 2004 the company had also fallen short of its production goals, but had *promised* that 2005 would be different, that it was capable of meeting demand. Both years the company blamed their production failure on few initial orders and shortages of the plant quingtao, indigenous to China, from which arteminsin is derived. The shortages raised questions like, is there a better drug, one that isn't dependent on an over-harvested plant?

Recently a group of scientists at University of California, Berkeley bioengineered yeast, Saccharomyces cerevisiae, to produce a precursor to arteminisin. The process involves the enzyme amorphadiene synthase that catalyzes the production of amorphadiene from farnesyl diphosphate (FPP). Cytochrome P450 then facilitates the next step of producing artemisinic acid. From artemisinic acid, the final step to the arteminisin compound is arguably cheaper than full synthesis of arteminisin would be. The research team says that this represents significant progress towards producing a more affordable treatment for malaria, although subsequent optimization of the process in order to produce a drug is likely 5 or 10 years away.

The researchers previously engineered E.coli to produce amorphadiene, an isoprenoid precursor to artemisinic acid, in research that was published in 2003 in the journal Nature Biotechnology; "Engineering a mevalonate pathway in Escherichia coli for production of terpenoids" (published online June 1, 2003), described here on the Berkeley press release site. At the time, the principal investigator Jay Keasling noted: "By inserting these genes into bacteria, we've given them the ability to make artemisinin quickly, efficiently and cheaply, and in an environmentally friendly way. Although E.coli replicates faster than yeast and can churn out more of the desired compounds, this next step, transformation of amorphadiene to artemisinic acid, turned out to be accomplished by cytochrome P450, a cellular membrane enzyme that functions in yeast but not E.coli. Keasling commented on the fortuitous research environment that led to the latest research:

"We reached our goal early, thanks to a number of miracles: The first gene Dae-Kyun isolated was the right one, the gene was functional in yeast, the gene's enzyme did in one step what we thought took three enzymes, and the artemisinic acid it produced didn't interfere much with the cell".

The research advances progress towards lower cost arteminisin production, which would potentially lower the cost of arteminisin combination therapy. Hopefully, this method, and/or vaccine development, along with existing technologies like prevention and bednets, will eventually help abate malaria. As much as the spread of malaria is a scientific challenge, it is also a political and economic challenge, although arguably a more sure-fire scientific solution would ease the politics.The research is supported by multiple organizations, and UC Berkeley has issued a royalty-free license to both OneWorld Health and Amyris to develop the technology to treat malaria. Africa Malaria Day is April 25, 2006


In addition to the article on malaria treatment progress listed above, Acronym Required also wrote about malaria vaccination development via private-public funding schemes for malaria vaccine development in Vaccine Development for Infectious Diseases. One World Health and Jay Keasling were also mentioned in a short post on Codon Devices.

Nuclear Future's So Bright

About sixty years ago the first atomic test brought to fruition Roosevelt's nuclear program. Posthaste, a group of Manhattan Project scientists urged policies of non-proliferation. The scientists must have been jubilant about their technological success, so the turnaround to hand-waving caution, was remarkable. It was almost as thought they had thought ahead of time about the dangers of the science but were driven to do the experiments anyway. Needless to say, once unleashed, the nuclear technology thrived. Weapons and civilian applications of nuclear energy proliferated despite the scientists' caution.

Then came Three Mile Island and Chernobyl.

Twenty years ago an explosion and fire at the Chernobyl power plant in the Soviet Union unnerved a world that had grown accustomed to relying on nuclear energy. Through the Cold War, people got used to living with the alarms of air raids, but the ultimate containment of nuclear weapons. The accident at Three Mile Island in Pennsylvania had given ample warning of the type of accident that could happen, but Chernobyl truly frightened the world. In May 19, 1986, Time magazine reported on the wide repercussions of the accident:

  • In Italy livestock that arrived from Eastern Europe were returned because radiation levels in the animals tested too high.
  • In Japan milk and water were found to be contaminated.
  • In Ottawa rain was found to have six time the amount of radiation than is safe for drinking water

In the US traces of radiation were found in ther Pacific Northwest and New York. People were concerned about drinking water. Donald Macdonald, Acting Assistant Secretary of health said, in what appears to be a more candid era: "I would drink it, and that's what the guidelines say, but I would prefer not to drink it."

A Financial Times reporter last week took a "holiday" in Chernobyl, where the tour business now apparently thrives. The author choice of vacation was paradoxical, perhaps a flurry of "publish and perish". He sallied forth:

"I paid $280 for a day with one personal guide and a second, official guide in the exclusion zone, which gave us freedom to roam pretty much where we wanted..." [and] "another $20 on what is locally known as "honey" - bottles of spirits and boxes of chocolates to ease the way through the several checkpoints on the way to the site."

The scene he describes is hardly inviting (and I am an adventurous traveler): "radioactive scrap yards where hundreds of vehicles [trucks, helicopters] that were used in the clean-up were parked in neat rows then abandoned". "Rust and corrosion [seeps]", from the hulking Reactor Four's "cracked and unstable" sarcophagus. Hundreds of workers still worker there for "two hours at a time", although the hundreds of so-called "bio-robots" who were hired to clean up after the initial disaster, have come and gone. Tour guides carry Geiger counters.

Nuclear energy has a wide array of supporters from business and science sectors. It's promoted as clean, cheap energy. The public is growing less wary of nuclear alternatives; with today's oil shortages, yesterday's nuclear catastrophes are easily forgotten.

In the decades since the last nuclear incident, the public has forgotten the terror of the accident. People are increasingly swayed by businesses that see opportunity in softening public opinion. To aid the perceptions of safety, some papers are reporting an abundance of wildlife inhabiting areas close to Chernobyl, as if the arrival of stray dogs and flower's in a radiation zone should stay our concerns about the renewed enthusiasm for all things nuclear.

The International Atomic Energy Agency (IAEA) issued a report last autumn, which said that deaths from Chernobyl would number about 4,000. However, Greenpeace writes in a recent report that that number is highly underestimated. The Greenpeace data places the actual numbers at 270,000 cancers and 93,000 fatal cancer cases directly caused by Chernobyl. On April 18, 2006: Greenpeace published "Chernobyl Catastrophe Consequences on Human Health". The report refutes the IAEA, and accuses it of "whitewashing" the data to promote nuclear energy. Among other things, Greenpeace faults the IAEA with deriving data from limited subsets of effected populations. One criticism is that IAEA notes that 212 of 72,000 clean-up personel died, but Greenpeace says that the more accurate number of "liquidators" or "bio-robots", was 600,000. Accurate data sets are essential for making public policy and if Greenpeace' contention is true, such data manipulation is unconscionable.

Nuclear technology continues to be propagated for political aims. The U.S. recently agreed with India to supply that country with enriched uranium for their domestic energy program. Congess has yet to debat the deal, but commentators expect it to go through. As nuclear energy is considered, so is nuclear war. Alarmingly, the U.S. is rumored to be eying Iran as a potential nuclear target, a report that the administration fervidly denies.Iran announced with fanfare yesterday that they produced enriched uranium which worries members or the U.S. Congress because India and Iran are embarking joint naval exercises in India.

Nuclear technology has the potential to be useful as well as lethal. Although scientists like those on the Manhattan Project, as well as politicians are rarely chastised when they only remember to criticize the repercussions of their experiments after the fact, we should remember the lessons we all learned - us and them. We understand very clearly dangers inherent with this technology and we have time now, before the clean-up, to consider the best ways to employ our power.

Sea Change or Littoral Disaster

Believe That? I've An Island To Sell You...

Islands always seemed like the ultimate luxury item, toast your first business deal with lunch, celebrate your genius with champagne and dinner, and when you finally reach the pinnacle of success, buy an island. If not your own island then maybe an estate that you call a "the bungalow", with an exclusive beach to escape the hubbub of work, no deadlines, only the warm sun, gently lapping water, and soft sand to dig your toes into. Quintessential relaxation. You know the places -- with the private boat docks, dozens of bedrooms, turrets here and there, golf course-like lawns, and helicopter pads.

Perusing the news in this getaway state of mind on these chilly December-January-February-March-April days though, any advertisement for a beach vacation seems attractive. Even a gratuitous palm tree at the top of an online airline ad has me pining for warm sand and azure seas. Then there's the full page NYT ad for St. Regis resorts and residences in Florida. "Couture living" it brags, summoning the languor of luxury in a not so understated way: "Introducing unparalleled oceanfront residences...exquisite design...bespoke lifestyle...enviable address." It's the quiet escape that shouts you've arrived.

Alongside the come-hither text, a woman perambulates through the surf in a white evening dress, a take no prisoners expression on her face, a box suitcase in hand, and a white-gloved attendant trailing behind with the luggage. The photo seems inspired by Jack Vettriano's Oh, Happy Days. But the vignette nags uncomfortably, despite the cold of the day and the rain pounding against the window. There is a threatening amount of ocean in the photo, a montage of water up to the well-off vacationer's shins, tugging at her fancy clothes and fashionable clunky leather suitcases. Vettriano didn't do this to his subjects, he placed them safely on solid sand to dance. And as reports of glaciers melting and oceans rising pour in, wading through water in your evening wear, even with a lot of gumption, could be a not so happy harbinger of things to come.

I'm not the first to think that island properties and beach front resorts in Florida are worrisome, but I find especially discomfiting the insouciance of the ad's presentation, its inadvertent reflection of all too common attitudes about global warming. Of course people with business stakes in islands wave off my concern. My queries to online purveyors of island properties quickly yielded e-mail brochures informing me that business was just fine.

While I can understand the positions of realtors who have a livelihood to protect, I don't understand those who dismiss global warming without such businesses. It would be in their best interest to fight against global warming. In a letter to the editor of the Los Angeles Times June 22, 2005 regarding climate change, someone suggested that people interested in the "facts rather than liberal scare tactics", should read Crichton's "State of Fear." Someone could sell him an island. What's striking is that the cocksure writer hails from Surfside, California. While Surfside is not Florida or Louisiana, as you can see on the map it looks to be on a small peninsula between an ocean and a bay. A luxurious vacation home today, water gently rolling in tomorrow?

Willing the Unwilling to Change

It's tempting to hope that only a few lost sheep doubt climate change, that only White House and Senator Inohe have been bamboozled by Crichton's "State of Fear". But many people consider Crichton's book to be so well argued that it is suitable for non-fiction climate discussions. This, despite the fact that Crichton himself writes in his book contains 'real footnotes' but the story is fiction.

In a casual discussion about global climate change recently, more then a few of the dozen or so participants said that there was not enough evidence for climate change to support taking steps to lower carbon emissions. To bolster their arguments they of course quoted Crichton, and George Will, who rhetorically rolls his eyes, throws his hands in the air and complains that first the scientists thought it was global cooling, and now they say it's global warming. When scientists aren't being wishy-washy, he says, they don't have any data.

It takes a concerted effort to assert that there's no data. One must steadfastly ignore decades of evidence from all the corporations who acknowledge the evidence. When oil companies such as Shell, and British Petroleum (BP) admit to dangerous global climate problems (BP in 1977), how can citizens who don't own an oil companies deny it? And not only do they deny obvious evidence, they have a rebuttal for potential solutions too. Carbon reduction is too expensive they say, ignoring the cost of denying climate change.

They brush off the fact that businesses, insurers, and investors are busy adjusting their strategies to deal with the problem. Organizations like Ceres, and the Carbon Disclosure Project, which Acronym Required wrote about here monitor and lower carbon emissions. Insurers and investors know that any business not paying attention is a risky investment.

Mr. Will and his ilk carry the proof of active intelligence, degrees from top schools and positions with bonuses and/or prestige. You want to trust that they're sincere and if they had just taken one more science class we could all band together in recognizing the urgency of the problem. But as the evidence spans decades and the tenor of the climate rhetoric remains relentlessly constant, it's obvious that this is a game of posturing, where roles are defined, for and against. This is a game with a structure defined to frame many decades of disagreement. It's not so much a path to resolution as a face-off like a couple of gangs of boys in a schoolyard with shoving and stare-downs. Climate change denialists aren't unlike those belligerent bullies daring the next geek to call them on their roughshod ways. Predictably, should one point to the fallacies in their argument of the day, they remain defiantly unconvinced. But they're not looking to be convinced.

Long ago, the media and some scientists cemented the idea that this was a simple split between those they characterized as oil company shills and those they characterized as environmentalists. We are conditioned to think that for every side there is an equal and opposite side. Our inclinations are exploited by the oil companies such as Exxon Mobil, who have paid "skeptics" to instill doubt in global warming.

Tuvalu Today, Gone Tomorrow?

Each side routinely calls the other the same names, so the incurious, or busy, or intellectually preoccupied don't have to miss a beat as they parrot back the accusations of the other side. Tuvalu, whose highest point is 5 meters above sea level, is called greedy (as many would accuse the oil companies of being) because it threatened to sue the U.S. and Australia for environmental negligence. One op-ed writer at conservative PR organization CEI accused Tuvalu of trying to exploit global warming with the "phony neck brace of 21st-century litigiousness". Oil company advocates accused a collective of states in the U.S. who legally demanded federal action to reduce emissions of trying to ruin the economy via "pseudo-tort intimidation suits".

Each headline that shows more evidence of warming is greeted with hope from those who believe that the naysayers really, really do need one more piece of evidence to convince them. Then the barrage of squawky letters to editors follows from the people who insist the science is all flawed. All sides are fiercely engaged in this disagreement, which is undoubtedly more pleasant then having to change, since everyone can stall together as they wait for another headline.

The back and forth is predictable. In 2002, when Tuvalu threatened to sue, their plight had been documented since at least the 1980's when the media began to report the rising seas and global warming with titles that are familiar today..."Tuvalu's...Sinking Feelings", appeared again and again.

Similarly, the demise of the coral reefs due to bleaching and other causes has been documented at least since the 1980's when large parts of the Caribbean reefs died off. And there is the always increasing, always alarming rate of glacial melting. We need no more evidence. We have decades of studies indicating that our lives will change, but its easier to wait for another headline and hope a miracle intervenes, or eventually government action.

Cognitive Dissonance

Even those who have the most immediate, perilous stake in global warming are sometimes reluctant to change, as Nature reports this week on Tuvalu. The Nature reporter noted that some Tuvalu islanders, as affected as they are by global warming "refuse even to talk about climate, or dismiss it with a weary wave of the hand.", and that "frequent workshops on climate and the dangers of accelerating sea-level rise fail to provoke a sense of urgency. (Samir S. Patel: Nature: 440, 734-736, 6 April 2006: "Climate science: A Sinking Feeling").

For Tuvaluans this must be the most difficult subject to face -- they will need to leave their homeland. But we cannot not feel too removed. We will face equally difficult life changes. As the vacationer at the St. Regis Resort wades through the surf in Florida, and as the Tuvaluan islanders "sink" up to their knees on the "main street", someday we will all notice that their fates are entwined with ours with global climate change.


Some related Acronym Required articles:

Business and Climate Change: "Carbon Emissions Disclosure Project"

Ice core research to study atmospheric conditions 650,000 years ago: "Holocene Days"

Politics and climate change: "Will Loose Lips - Or Global Warming - Sink Ships?".

Carbon emissions regulation after Katrina: "The Environment & Katrina-Slick Oil Fallout"

Drought in the "Amazon", and in "Australia".

Science research communication and climate change: "Research, Politics and Working Less", and "Science Communication".


June 20, 2006: The New York Times writes a piece on erosion and global warming titled Next Victim Of Warming: The Beaches"

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