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2 0 - 0 3 - 2 0 0 6 Manhattan Nuclear Nightmare
What if New York City was dirty bombed? We'll pop some pills and see the "walking dead"
New Scientist In 2004, a US government-funded working group published an estimate of the number of radiation casualties that would follow a 10-kiloton detonation in a mid-sized city of 2 million, the size of Washington DC (Annals of Internal Medicine, vol 140, p 1037). The numbers make for sobering reading: 13,000 killed immediately; 45,000 facing certain death regardless of treatment; 255,000 at risk of dying without hospital treatment; and a further 140,000 in need of observation. It is the quarter of a million lives that could be saved that are exercising the minds of US policymakers. All of those casualties will be suffering from acute radiation syndrome, otherwise known as radiation sickness. All are potential survivors, but at present there would be little that doctors could do for them. Most of what is known about radiation sickness comes from animal studies and accidents, and from medical records from Hiroshima and Nagasaki. The syndrome is a collection of symptoms that get progressively worse with increasing exposures. The simplest measure of exposure is a unit called a gray - the number of joules of radiation energy absorbed per kilogram of tissue. Any exposure above 2 grays or so is deadly serious. People irradiated to this level or higher quickly get sick, then get better again. However, this "latent phase" is only temporary. Some time later, from a few days to a month, they fall ill again, and often die. Not surprisingly, the more radiation you absorb, the more organs are involved, the quicker the immediate symptoms come on and the shorter the latent phase. The body's most susceptible vital tissue is the bone marrow, specifically the stem cells within it that give rise to new blood cells. These are impaired at doses as low as half a gray and are usually wiped out completely and permanently above 5 grays. When the stem cells die, blood-cell counts - most critically those of neutrophils and platelets - start to drop, eventually plunging to zero after days or weeks. Without neutrophils, the first-responders of the immune system, radiation victims are at high risk of opportunistic infections. Losing platelets is also seriously bad news: without them blood cannot clot, leading to potentially fatal bleeding from even the smallest wound. Upwards of 5 grays, the gastrointestinal tract is also affected. Radiation kills any rapidly dividing cells, such as the ones lining the intestinal tract. The resulting damage can cause gut bacteria to leak into the bloodstream, where they overwhelm the already compromised immune system and cause septic shock. At exposures above 10 grays, the central nervous system is damaged too, and death is certain, with or without treatment. The standard treatment for radiation syndrome is "supportive care": blood and platelet transfusions, antimicrobials, fluids, anti-emetics and other "comfort measures". These treatments are better than nothing but are often not enough, and would be extremely difficult to deliver on a mass scale in the aftermath of a nuclear attack. Which means that despite receiving technically survivable doses of radiation, a large proportion of those 255,000 people will die. The US government is determined to shift the odds in their favour. "What we're aiming to do is to be able to treat every casualty," says Norm Coleman of the National Cancer Institute in Bethesda, Maryland, who has been helping the Department of Health and Human Services plan its response to a nuclear attack. The government is putting its money where its mouth is. In 2005 it awarded a total of $47 million to several groups of radiation researchers, including $29 million to the newly formed Centers for Medical Countermeasures against Radiation (CMCR). Their mission is to gain a better understanding of the biology of radiation damage, find faster ways of diagnosing radiation exposure levels, and discover better drugs. In July 2004 President Bush signed the Bioshield Act into law, committing $5.6 billion to counter nuclear, biological and chemical threats. And late last year, the government put out a call for companies to develop drugs that preserve and restore neutrophil counts in radiation syndrome, with secondary emphasis on platelets. So far no such drugs have been approved in the US, but there are candidates. One obvious option is G-CSF (granulocyte colony-stimulating factor), a cytokine that stimulates the bone marrow to pump out new blood cells. Sold by Amgen of Thousand Oaks, California, to treat neutrophil loss caused by cancer therapy, G-CSF works by preventing the death of the bone-marrow precursor cells destined to become neutrophils, and by boosting their rate of proliferation. Even so, there are serious doubts over G-CSF's suitability for mass administration in the event of a nuclear terror attack. The drug is expensive, up to $400 per dose, and a patient would typically need daily doses for at least two weeks. It can't be left unrefrigerated for more than 24 hours. Worse still, although it has been given to thousands of cancer patients, side effects are common and can be severe, says Waselenko. So the search is on for better drugs. An ideal radiation countermeasure would be effective, cheap, and easy to make and administer. It would have a long shelf life, minimal side effects if given to someone who turned out not to need it, and would still work even if administered days after exposure. One drug, a steroid called 5-androstenediol or 5-AED, seems to hit most of those targets.
5-AED is cheap, chemically stable and apparently very safe. Developed by Hollis-Eden Pharmaceuticals of La Jolla, California, as an adjunct to chemotherapy, 5-AED was identified as a radioprotectant by Mark Whitnall of the Armed Forces Radiobiology Research Institute (AFRRI) in Bethesda, Maryland, in 1996. It is now being jointly developed as a radiation sickness drug by AFRRI and Hollis-Eden. Last October, Hollis-Eden announced that in their clinical trial 5-AED significantly increased platelets and neutrophils, without adverse effects, in a group of non-irradiated human volunteers. And in a study led by haematologist Gerard Wagemaker of Erasmus University in Rotterdam, the Netherlands, reported at the annual meeting of the American Society for Hematology in Atlanta, Georgia, in December 2005, 5-AED significantly reduced symptoms in irradiated rhesus monkeys and accelerated the recovery of their neutrophils, platelets, red blood cells and all-important stem cells. "This steroid exactly mimics the actions of [the platelet-stimulating cytokine] TPO and G-CSF combined - so far, the most effective combination of cytokines for radiation damage to the bone marrow," says Wagemaker. Although 5-AED is AFRRI's most advanced and, to date, star performer, it's not perfect. Like G-CSF, you need to get it to people quickly: it has yet to be shown effective if used more than a couple of hours after exposure. The drive to develop radiation countermeasures could have some everyday pay-offs. For one thing, drugs such as 5-AED might allow us to go back to nuclear power with more confidence. And as Wagemaker points out, ageing populations will become increasingly vulnerable to blood disorders, just as the supply of donors will be dropping. "It is expected that the number of platelet infusions that are needed will at least double in 10 years' time," he warns. |
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[Definitie:] "An ergogenic aid is any substance or phenomenon that enhances performance."
(Wilmore and Costill) 
