Medicine: Blood Simple

The Economist: Oct 11th 2007

Because they lack an essential component, blood transfusions may be killing some of the people they are intended to save

IF THERE were any sure bets in medicine, you might think that “blood transfusions save lives” would be one of them. But there aren't. Even though deaths caused in the 1980s by accidental HIV infection mean that donated blood is now screened meticulously to keep it free of infectious agents, there is still a nagging feeling that something is wrong.

In 2004, for instance, Sunil Rao of Duke University Medical Centre, in North Carolina, carried out a study of people suffering from acute coronary syndrome (a specific type of heart attack). One conclusion that could be drawn from his research was that unnecessary blood transfusions might be causing tens of thousands of deaths in America alone. Dr Rao found that patients who had had a transfusion because of a low red blood-cell count had an 8% chance of dying within 30 days. Without a transfusion, only 3% died. Those numbers need to be treated with caution. As Dr Rao points out, the patients who underwent transfusion were, on average, sicker and older than those who did not. Nevertheless, his study is not the only indication of something amiss.

In recent years, research has suggested that transfusion is not necessarily a good thing for patients suffering from serious injuries, for those who have undergone surgery and even for those who are anaemic. And a study carried out earlier this year found that critically ill children whose red blood-cell counts had dropped by half fared no better after a transfusion than those who did not receive one.

As a result of all this, questions are being asked about whether something happens to blood when it is banked that causes it to stop working properly. What that might be has remained a mystery. But it may be one no longer. A group of Dr Rao's colleagues, led by Jonathan Stamler, think the answer is a gas called nitric oxide—or, rather, a lack of it.

Out of gas

The main reason for giving a patient blood is that it carries oxygen. It carries lots of other things, too, such as glucose. But it is a lack of oxygen that will kill you quickest. However, as Dr Stamler points out, what determines whether transfused blood works as a treatment is not merely how much oxygen it is carrying, but whether that oxygen can reach the tissues that need it. This is where nitric oxide comes in.

Nitric oxide increases the flow of blood to tissues by dilating the arteries that penetrate those tissues. The best known example is the erectile tissue of the penis (Viagra works by sustaining the signal that the gas gives). However, it is not just penile blood vessels that nitric oxide relaxes. When a red blood cell reaches any tissue in need of oxygen it releases nitric oxide in order to dilate the capillaries. Only then can it deliver its cargo. And that is doubly true of the cells in stored blood since red blood cells become less flexible with age, and thus less able to squish into capillaries. Dr Stamler thus wondered if a lack of nitric oxide was causing the problems associated with transfusions.

What he and his colleagues discovered, and published this week in the Proceedings of the National Academy of Sciences, was that the amount of nitric oxide in stored blood does indeed decrease—and does so rapidly. Within a day of storage, blood loses 70% of its nitric oxide. After a few days, up to 90% has been lost.

A second paper in the same journal, by Dr Stamler's colleague Timothy McMahon, confirmed this result (in fact, it showed that the initial drop of around 70% happens within three hours of collection) and showed that it was not caused by the way blood is processed, but merely by the passage of time. Dr McMahon also established that stored blood does indeed lose its ability to dilate blood vessels.

Dr Stamler is in little doubt about the significance of these findings. Furthermore, he warns that putting blood lacking nitric oxide into the body does not merely dilute what gas is already present in the bloodstream. Blood that is poor in nitric oxide will scavenge the gas from other tissues, causing the vessels in those tissues to constrict. If the tissue in question is heart muscle, the result will be a heart attack.

These papers, therefore, make a strong case that a lack of nitric oxide is creating the problems with transfusions—though as Michael Strong, the president of the American Association of Blood Banks, points out, they do not settle the issue once and for all. That would require a proper, randomised clinical trial.

And therein lies the rub. Because blood transfusion is such an old practice (it dates back to 1818) it has never been subjected to modern clinical standards. Nobody is questioning whether car-crash victims, say, should have transfusions after massive blood loss. Without it they would undoubtedly die. But for those not threatened with exsanguination it is far less clear whether a transfusion is a good idea. There are no rules about when to transfuse and who to do it to. These are matters of judgment, and knowledge is typically passed from doctor to doctor.

The good news from this study is that the problem should be easy to correct. If nitric oxide is what is needed, it can be added to banked blood just before transfusion. As part of the project, Dr Stamler tried this with dogs. He found that old blood replenished with nitric oxide is as good as fresh blood at relaxing blood vessels. And that, he thinks, points to a bigger possibility than merely returning blood to normal. Blood boosted with nitric oxide might be used as a therapy for people who have had heart attacks by providing extra oxygen in the crucial minutes after an attack, before the affected heart muscle has died. At that point, blood transfusions would no longer be part of the problem: they would be part of the cure.

Some hard talk about towns

Cities and natural disasters
Some hard talk about towns

Oct 4th 2007

IT ISN'T just an urban myth: life in a city really is getting more dangerous, and the sources of peril are not just human ones like muggers and reckless motorists. A report by UN-Habitat, an agency responsible for human settlements, says the number of natural disasters affecting urban populations has risen four-fold since 1975.

Some of the reasons are obvious, others less so. As the world's population grows, people are crowding into mega-metropolises, where life's risks are horribly concentrated. The after-effects of a natural disaster can be especially dire in a vast, densely-packed area where sewers fail and disease spreads.

At a pace that no urban planner can control, slums spring up in disaster-prone areas—such as steep slopes, which are prone to floods, mudslides or particularly severe damage in an earthquake. Many of the world's cities are located on coasts or rivers where the effects of climate change and extreme weather events, from cyclones to heatwaves to droughts, are brutally and increasingly felt. Economic dislocation and human pain are also caused by events (like recent floods in the Indian city of Kolkata, see above) that are too small to grab global headlines.

But there is no reason for the sort of fatalism that regards disasters, and their disproportionate effects on the urban poor, as something that has “always been with us” and will inexorably get worse. (more...)

A barcode for every living thing

Name, rank and serial number
Biologists want to barcode half a million species in the next five years

Sep 20th 2007

THE tale of the unknown goby began in 1982 when Benjamin Victor, of the Ocean Science Foundation in Irvine, California, discovered an unusual fish in a reef in Panama. With only a single specimen he was hard pressed to prove it was a new species, so the fish remained, unnamed, on his desk for 25 years. Then, last year, he was sent an unusual fish larva. Using a new kind of DNA identification called barcoding he showed that it was a younger version of his mystery goby and that both specimens were, indeed, a new species. (more here)

This week an article about a huge project to barcode living species. According to one of those involved in the piece, Dr Baxter, several people have emailed saying I've over-egged things somewhat by describing Dr Hebert as having invented barcoding. This is, apparently, like "crediting Mr Kipling with inventing cakes: he didn't invent it but popularised it". That may be a fair criticism. But in my defense I would say Dr Hebert did identify a pretty neat gene to do the animal barcoding which has really led barcoding to take off.

Arresting evidence

State-of-the-art forensic technology is forcing us to face the reality that even our most applauded trade bans and moratoriums aren’t working. From ivory cell phones to shark fin soup, it’s all available—at a price.

By Natasha Loder. Conservation magazine.
July-September 2007 (Vol. 8, No. 3)

Inside a glitzy store in one of China’s port cities is a room that might shock you. Low lights, shiny glass, and mirrored cabinets: the room is a temple to ivory. It’s all available at a price, from tiny figurines to massive high-end carvings and even entire carved elephant tusks. A new report by the Environmental Investigation Agency (EIA) (1) in the U.K. says it’s a similar story all over China. Trade in ivory goods is flourishing, from key holders and chopsticks to pendants, bead earrings, and hankos. Given enough money, it is even possible to buy an ivory mobile phone. It all begs a simple but unsettling question: where does all this ivory come from 17 years after the international trade was halted? (Read more of this article here).

More reefer madness

Everyone warned me. I can't say I wasn't told. But motherhood is far more work than I'd imagined. So, in the last few months I've just produced two articles (and a beautiful bouncing boy).

The first was on cannabis research in the US, where scientists hoping to grow the weed for medical research have had to fight a long court case with the DEA. The latest news is that they've had an unexpected breakthrough, winning an important court case. The fight isn't over, by any means, and we shall have to wait and see if America's DEA agrees with court's decision that a professor of agronomy can be allowed to grow cannabis. At the moment the government maintains a monopoly in the growth of cannabis. This has restricted the supply of the weed to researchers.

Joint action

Mar 1st 2007
From The Economist print edition

A victory for American cannabis researchers

FOR almost six years Lyle Craker, a researcher who studies medicinal plants at the University of Massachusetts, has been trying to grow pot. Quite a long time, one might think, for a professor of agronomy—his students, presumably, have far less trouble. The difficulty for Dr Craker, though, is that he would like to grow marijuana legally, but the Drug Enforcement Administration (DEA) has so far refused to give him a licence. (More... subscription required)

The second piece was an article for a new journal called Ethos. The blurb describes it thus: "published three times a year and will be aimed at politicians, civil servants, think-tanks and other interest groups involved in delivering public services. Ethos will help lead and anticipate the public policy agenda, as well as stimulate debate on the future direction and challenges facing government and the wider public service arena." We will see. In any case, the commission, on the new Chinese eco-city of Dongtang was too interesting to pass up. The piece makes the point that even if this eco-city experiment is successful in builing a zero, or even low carbon city, it is just one of hundreds that China will be building in the near future. Depressingly, a project of such vision seems beyond any other country in the world. Dongtan is unique. The world needs thousands of these, not one. But as they say, a journey of a thousand miles...

Impending arrivals

Natasha Loder is on maternity leave.

Rocket renaissance

ALMOST two years ago, SpaceShipOne became the first privately-built vehicle to travel into space. Although the X-15 did something similar four decades earlier, the simple, safe design and low cost of SpaceShipOne was significant—for the first time the cost of a spacecraft fell within the price range of companies and wealthy individuals, rather than just governments. That’s one reason why today at least half a dozen private spaceships at various stages of design and construction. Today, rocketry is going through a renaissance.

Stalking through the corridors of the International Space Development Conference (ISDC) in Los Angeles this year, are the men who are going to build a new generation of spaceships. While promises about cheap space travel for the masses have been made before, this time things seem different. Besides the birth of SpaceShipOne, there has been a recent shift in US legislation to encourage personal spaceflight by simplifying government licensing requirements, straightening uncertainties over liability issues and allowing paying customers to fly at their own risk in novel craft that might be dangerous.

Most importantly, though, there is money. Lots of it. More than $1 billion has been committed on ships and infrastructure. The state of New Mexico, for example, has recently started work on a purpose-built $225m spaceport, of which the state has committed $135m to funding, even though it has nothing yet to fly. The spaceport is intended to provide a launch pad for commercial operations of the second-generation suborbital vehicle SpaceShipTwo—currently being designed in Mojave, California and which may start test flights as early as next year. The commercial development of this vehicle, in itself, is costing its financial backers, Virgin Galactic based in London, $240m. One study suggests that after five years of operation, New Mexico spaceports will have led to $1 billion of spending within the state.

Meanwhile, in Dubai, another new spaceport costing $265m was recently announced by space tourism company Space Adventures, based in Arlington, Virginia. Of this sum, $30m has been committed. (Space Adventures itself, in the last five years, has made $120m in orbital spaceflight sales—taking wealthy businessmen such as Dennis Tito, to the International Space Station with the help of the Russians.) Many other spaceports, too, are being planned around the world for an anticipated new generation of tourist vehicles, some of which are still on the drawing board or have only recently come off it. But overall, the signs lead many to suspect that a lot of money is being spent on rocketry and infrastructure that has not yet been revealed.

All this enthusiasm is being generated by plans by individuals and private companies to build a variety of suborbital spaceships--craft that travel just to the edge of space and back again. Which one, though, is best and who will succeed? This is the topic of a two-page article in this week's Economist. There is also a useful chart comparing all of the main designs.

I've been researching this piece for some time and a large array of overmatter has accumulated. I'd like to thank Charles Lurio, a space consultant, and Roger Launius, a curator at the Smithsonian Air and Space Museum, for their help as their comments were left on the cutting room floor. Charles is particularly knowledgeable about hybrids and solids. He also reckons that the Space Adventures vehicle, still in design, is a solid-based rocket.


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Rocket renaissance
The Economist
May 11th 2006 | LOS ANGELES
The era of private spaceflight is about to dawn

TWO years ago next month space travel underwent its Wright-brothers moment with the first flight of SpaceShipOne. The roles of Orville and Wilbur were played by Burt Rutan, who designed the craft, and Mike Melvill, who flew it—although they were ably assisted by Paul Allen, one of the founders of Microsoft, who paid for it. Of course, history never repeats itself exactly. Unlike the brothers Wright, who were heirs to a series of heroic failures when it came to powered heavier-than-air flight, Messrs Rutan and Melvill knew that manned spaceflight was possible. What they showed was that it is not just a game for governments. Private individuals can play, too. (more...)

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Overmatter:

XCOR on why it chose an air-launched suborbital
Jeff Greason, president of XCOR Aerospace, a small aerospace company based in Mojave, California, is developing a two-person, ground-launched suborbital rocketplane. Ground launch, he says, is technically more difficult but has significantly lower unit operating costs. “We are doing it this way because our engineering tradeoffs lead us to believe it is optimum for us for our market, resources, for the skills we have. Does that mean everybody else’s idea is bad? Of course not.” The XCOR vehicle, which will be a derivative of a previous design called the Xerus. As of last October, the company has money from private investors to start work.

Space Adventures on its vehicle plans
Of the six most prominent vehicles being developed (see chart), two are launched from the air. SpaceShipTwo will launch on a purpose-built high altitude aircraft known as Eve, built by aviation designer Burt Rutan. And although plans for the Explorer have not been fully disclosed, Eric Anderson, president and CEO of Space Adventures, says it will launch from the top of a high-altitude Russian research plane the M-55X. The project, he says, will be fully funded by a venture capital group belonging to wealthy, space-enthusiast and entrepreneurial Ansari family. The Myasishchev Design Bureau, an experienced Russian aerospace organization based near Moscow, with oversight from the Russian Space agency, will build it.

Rocketplane on the stability of its XP
At first sight, the notion of converting a Learjet to a suborbital vehicle fills some with horror. However, as Charles Lauer explains, there is actually very little left of it except the fuselage. “Starting with the existing Lear gave us a frame of reference to be able to build from and saved us a year in terms of schedule,” he says. It has a new delta wing, a new v-tail, and wind tunnel studies show it has “natural stability” on re-entering the atmosphere says Mr Lauer. SpaceShipOne solved the problem of stability on re-entry with a revolutionary technique of flipping its wings in half—something called the feather. Mr Lauer says the XP has this but “without having to reconfigure our airplane twice in the course of a flight profile and that’s a more sensible way to fly”.

George Whittinghill, chief technologist for Virgin Galactic, responds, "SpaceShipTwo can re-enter in any attitude, even upside down. The feather acts like a shuttlecock, and will right the ship as soon as it hits air, without any action from the pilot. I seriously doubt that the Rocketplane can re-enter in any attitude, hands-off, righting itself. Its attitude control jets will have to position the ship just right, or it will get into trouble later on during the entry.

Dennis Tito on liquid fuels
Dennis Tito, an entrepreneur and the world’s first space tourist, says ultimately liquid fuel will make a suborbital more reusable because it is possible to “gas and go”. In other words, operations can be more aeroplane-like and this will lower costs. XCOR’s ship seems quite likely to be the smallest, and cheapest, of all the new suborbital ships. Although no timeline has been announced, one potential customer reckons that they could fly within a year and a half. The ship is also intended to fly four flights per day.

Charles Lurio on rocket design
With their premixed fuel and oxidizer, solid propellant systems have always raised safety questions. They’re tricky systems to master, as evidenced by the literally explosive difficulties that the then-Soviets had in developing them for ICBMs. As a result the USSR retained primarily liquid fueled missiles long after they were minimal parts of the US arsenal. NASA, driven by the desire to get the Space Shuttle program funded, convinced itself that solid boosters (with a lower upfront development price) were acceptable despite long-standing anxiety about the safety of putting people atop them. Of course, ‘turning off’ a solid in an abort condition - let alone restarting it in flight - is essentially impossible. Hybrids do appear to have a higher safety potential, not merely by separating fuel from oxidizer but because they can be shut off by cutting off the flow of oxidizer. As with solids, however, they have much larger combustion chambers than do liquid motors. That volume effectively ‘stores’ combustion energy, which, as one person dryly put it, “can go somewhere inappropriate in a failure [condition].” But the greatest unease that I and others have with the hybrid results from the relatively miniscule amount of existing experience in building and operating them compared to either solids or liquids. As I’ve noted, Brian Binnie had to cope with significant accelerations and vibrations while SpaceShipOne’s motor was firing (see page 60 of the February 6th Aviation Week). There are design and flight adjustments that likely would ameliorate those effects for commercial passengers. By contrast, while a solid’s acceleration can also be moderated (though not in real-time) it essentially unavoidably produces what’s not-so-fondly referred to as the ‘paint shaker effect.’ Of course, reentry forces (Mr. Binnie experienced 5.5g’s) are not directly dependent on the ascent propulsion system, and are malleable with aerodynamic design and chosen flight paths.Some of the initial passengers on the suborbital flights will want to primarily liquid fueled missiles long after they were minimal parts of the US arsenal. NASA, driven by the desire to get the Space Shuttle program funded, convinced itself that solid boosters (with a lower upfront development price) were acceptable despite long-standing anxiety about the safety of putting people atop them. Of course, ‘turning off’ a solid in an abort condition - let alone restarting it in flight - is essentially impossible.

Hybrids do appear to have a higher safety potential, not merely by separating fuel from oxidizer but because they can be shut off by cutting off the flow of oxidizer. As with solids, however, they have much larger combustion chambers than do liquid motors. That volume effectively ‘stores’ combustion energy, which, as one person dryly put it, “can go somewhere inappropriate in a failure.” But the greatest unease that I and others have with the hybrid results from the relatively miniscule amount of existing experience in building and operating them compared to either solids or liquids.