If the unlikely becomes likely: Medical response to nuclear accidents

What does exposure to high-dose radiation do?

Exposure to short-term high-dose radiation has profound adverse effects in humans. People exposed to more than 1 to 2 gray of radiation typically require immediate medical intervention (American College of Radiology, 2006; Gale, 1987; Mettler and Upton, 2008). This amount of radiation is equivalent to about 200,000 chest X-rays. The Chernobyl victims whom we treated had received doses of 1 to 2 to about 15 gray—or the equivalent of 2,000,000 chest X-rays. It should be noted that doses less than 2 gray also produce important biological effects, such as gastrointestinal symptoms and decreases in blood cell levels, but these are modest and typically do not require immediate medical intervention. Also, any doses that exceed background radiation, which is the radiation that is found in one’s natural environment, will increase a person’s lifetime risk of developing cancer.

In considering these direct, dose-dependent adverse consequences of radiation exposure, it is important to note that unintended radiological exposures often occur in the context of other injuries, like explosions and fires (Gale, 1987). Concussive and thermal injuries confound the consequences of radiation-induced damage to humans. For example, many of the Chernobyl victims had severe thermal burns in addition to skin damage from radiation. In some instances the extent of thermal injuries—rather than radiation effects—determines survival. In the case of an improvised nuclear device (a “dirty bomb”), concussive or projectile injuries will likely account for far greater morbidity and mortality than radiological effects. However, the political and psychological effects of the radiological component of an improvised nuclear device are likely to be of far greater consequence because of the deficit in governmental and public understanding of radiation effects.

Physicians generally distinguish three high-dose acute radiation syndromes: gastrointestinal, bone marrow, and central nervous system (reviewed in American College of Radiology, 2006; Centers for Disease Control and Prevention, 2008; Wolbarst et al., 2010). From a medical intervention perspective, bone marrow effects are the most important because this is where prompt, effective actions can save lives. People with gastrointestinal acute radiation syndrome will usually recover, whereas those with central nervous system effects will usually die.

Medical intervention

The medical approach to radiation-induced bone marrow failure is determined by the severity and the estimate of how long the blood cell production will decrease, including red blood cells (needed for oxygen transport), white blood cells (needed to prevent infections), and platelets (needed to prevent bleeding). Red blood cells are relatively easily replaced by transfusions. In fact, the United States has a sufficiently large inventory of red blood cell units to respond to a moderate-size event like Chernobyl. Preparedness obviously goes out the window when we consider a catastrophic event like the intentional detonation of a nuclear weapon over a populated area. To respond to deficient bone marrow production of red blood cells—and to ultimately stimulate the production of these cells—cloned hormones can be used.

In terms of radiation, it is more difficult to correct a reduced production of white blood cells, specifically granulocytes (needed to prevent bacterial and fungal infections). Antibiotics and anti-fungal drugs are typically given to prevent or treat infections. Ionizing radiation also can activate latent infections of DNA-viruses, especially herpes viruses and cytomegalovirus; anti-viral drugs, or sometimes antibodies, can be administered in such cases. Unlike transfusing red blood cells from normal donors, transfusing granulocytes is technically demanding and of unproved benefit. The key recent progress here is the molecular cloning of hematopoietic growth factors to stimulate the production of granulocytes (a type of white blood cell) (reviewed in MacVittie et al., 2005). We used this approach successfully in Goiania, Brazil, where, in 1987, two men stole a cesium radiation therapy unit to sell for scrap metal—not knowing, of course, it was radioactive; they transported this throughout a city of about one million people near the capital city of Brasilia (Butturini et al., 1988). The effects were similar to what could be expected after detonation of a medium-size improvised nuclear device.

But there is a caveat to using cloned hematopoietic growth factors: This approach can only succeed if sufficient numbers of immature bone marrow cells survive radiation damage. This survival might be possible after low radiation doses, but not after very high doses. When few or no target cells survive, the medical approach shifts to bone marrow replacement—and this was the case for some victims of the Chernobyl accident.

When platelet production is reduced, platelet transfusions and cloned hematopoietic growth factors, which stimulate platelet production, can be used. Platelet transfusions are not as available as red blood cell transfusions. The United States could cope with a modest-size radiological event, like an improvised explosive device, for example, requiring platelet transfusions, but it could not respond to a moderate-size event, like a tactical nuclear weapon, and certainly not with a catastrophic event, such as a nuclear attack. Hormones that stimulate platelet production are less effective than those that stimulate granulocyte production and have not been extensively evaluated in human radiation victims. Several other cloned hematopoietic growth factors that stimulate bone marrow cells are available. It is uncertain, however, whether this approach will be useful in a radiation accident.

Replacing the bone marrow

No dose of radiation a human can otherwise survive (less than about 12 to 15 gray) kills all bone marrow cells (Baranov et al., 1994). However, because sometimes so few bone marrow cells survive radiation exposure, the time needed for recovery to occur without intervention may be impossibly long: two or more months. In this instance, bone marrow replacement would need to be considered. But who should be the donor? Ideally, the victim would have a genetically identical twin or someone with the same genes that control the acceptance and rejection of transplants, so that a transplant would not be rejected; this system is known as the human leukocyte antigen system, or HLA, which is a genetic system consisting of proteins that are typically shared among siblings or other family members (these proteins discern their own cells from foreign cells). Unfortunately, HLA matches occur in less than 10 percent of the cases in which a donor is needed.

There are several alternatives to replacing radiation-damaged bone marrow. One is to transplant bone marrow or blood cells from volunteers whose HLA-type has been determined and stored in global databases. Globally, there are now more than 14.8 million donors (http://www.bmdw.org/). The downside to this approach is that it can be time-consuming to locate the potential donor and to perform additional genetic testing. The volunteer may no longer be willing to donate or may have been exposed to radiation. Another alternative is to use HLA-typed blood cells obtained from umbilical cords. About 650,000 of these units are frozen and stored in several sites worldwide with data on their types kept in a central computerized database. This approach can be quicker than searching for a volunteer, but there are fewer potential units and there is no guarantee that they will not be irradiated when a radiological event occurs. People with bone marrow diseases, like leukemia, have had comparable or slightly inferior outcomes with alternative donor sources to those who have had transplants from HLA-matched sibling donors (Arora et al., 2009). These alternative donors have not been used for radiation accident victims, so their effectiveness is unknown.

In contrast to immediate responses (antibiotics, transfusions, cloned hematopoietic growth factors, etc.), which may or may not be beneficial but are unlikely to be harmful, a strategy to replace the radiation victim’s bone marrow may worsen the person’s condition and even decrease the likelihood of survival. Reasons for this are complex. For example, the victim may have received a sufficiently high dose of radiation to allow a medical team to predict a substantial risk of death from bone marrow failure, but not enough radiation to prevent the person from rejecting a bone marrow transplant from a donor other than a genetically identical twin. Doctors are left with the paradox of having to give the victim more radiation or immune-suppressive drugs (or both) to prevent rejection of the transplant. These drugs can have adverse effects on tissues, especially those already damaged by radiation or collateral injuries like thermal or concussive damage, as was mentioned. There are also political and psychological barriers to potentially adverse interventions of this nature in an accident setting. For example, some governments will find the notion of iatrogenic deaths unacceptable even if the net effect is to save more lives.

Another paradox is that even if there is success in overcoming graft-rejection, a different complication could potentially be caused: graft-versus-host disease, in which immune competent cells in the transplant attack tissues and organs of the radiation victim. Thus, in attempting to prevent death from bone marrow failure, doctors may injure or kill the victim by causing graft-versus-host disease. The calculus for determining whether and when to replace the bone marrow in a radiation victim is complex and controversial. Various, sometimes contradictory, guidelines are proposed by experts to identify persons most likely to benefit from a transplant (Fliedner et al., 2008; US Department of Health and Human Services, 2008). Fundamentally, this is a benefit-risk calculation that needs to be made on the basis of an individual, rather than on a population. After reviewing data from Chernobyl and other accidents, we think that only a small proportion of a cohort of radiation victims, probably less than 5 percent, even qualify for a detailed consideration of whether a transplant is appropriate. Typically these will be persons exposed to a dose of more than 8 to 10 gray.

There is, unfortunately, little to say regarding victims exposed to more than 12 to 15 gray of ionizing radiation. These people are likely to die, and medical resources need to be focused on victims with a reasonable likelihood of survival.

Public policy implications of medical data

There are several possible scenarios that policy makers, the public, and medical specialists need to consider when preparing a response strategy to a nuclear event. These include:

1. A state’s accidental detonation of a nuclear weapon, or a “rogue” state’s intentional use of a nuclear weapon for strategic or tactical purposes.

Although non-state actors might secure a nuclear weapon by covert means, it is unlikely they would have a meaningful delivery capability. Prevention is the optimal medical strategy to the intentional detonation of a nuclear weapon. In nuclear disaster scenarios developed by the US military and consultants like the RAND Corporation, medical teams would respond to a 1 megaton nuclear weapon detonated over 1 kilometer of a densely populated area; the medical resources needed for even a minimal response in such a scenario are unachievable. The expert consensus is that there is no effective or strategic response to reduce causalities and deaths.

2. Improvised nuclear devices, whereby a conventional explosive device is contaminated with one or more radionuclides, pose a different problem.

It is unlikely that immediate medical intervention would be required for radiation victims from such a device. There may be a risk of unacceptable long-term radiation exposure, but this can be mitigated by decontamination, shielding, and, if needed, short- or long-term evacuation (National Council on Radiation Protection and Measurements, 2008). Such devices are employed by terrorists for predominately political and psychological purposes. Although few people will be harmed health-wise, there is likely to be widespread confusion and hysteria, which will lead to inappropriate and possibly dangerous reactions.

It is vital that policy makers and the public be educated on what radiation from an improvised nuclear device can and cannot do—and the conditions under which relevant effects occur. For example, under almost all scenarios, it is better not to evacuate—that is, people should stay in the building where they find themselves at the time of attack. Evacuation, by decreasing shielding, usually increases exposure of the population at risk.

Also necessary in such an event is a solid, well-informed command and control structure and a panel of credible, independent medical experts that can work together to provide instructions and information to the public in the case that government credibility is compromised (consider the Soviet government and Chernobyl). These conclusions also apply to an improvised radiological device.

3. Accidental or intentional, terrorist-orchestrated public exposure to a conventional radiation source (such as a radiation therapy unit, which could be purchased, stolen, or abandoned and then recovered).

The radiation-induced heath effects are likely to be small, but the political, psychological, and economic damages may be great (National Council on Radiation Protection and Measurements, 2001). As in the dirty-bomb scenario already mentioned, educating policy makers and the public is vital. The approach should not be in the form of a nationwide government-sponsored ad campaign, but a carefully conceived, long-term plan within the public education system to provide lessons on radiation. Because radiation biology is absent from the medical curriculum, health-care givers, including physicians, also should be required to take an informational course, similar in nature to what several US states require for response to child abuse, breast cancer therapy options, and management of Alzheimer disease.

4. Accident at a nuclear power station.

In terms of nuclear power stations, Chernobyl was, of course, an exceptional event. Most serious accidents at nuclear plants involve a small number of workers. There are extensive guidelines for dealing with these incidents that work reasonably well. There are also well-established command and control procedures and knowledgeable and experienced personnel who rehearse these potential incidents. Unfortunately, the high standards, at least on paper, in most developed countries may not apply to all stations, especially in developing countries, where many nuclear plants are planned or are currently being developed. Because an accident anywhere is an accident everywhere, developed countries should offer expert medical and accident planning advice to their neighbors. This is being done to some extent by the International Atomic Energy Agency (IAEA), but there is no substitute for the one-on-one interaction of responsible medical personnel before an accident. As always, prevention of accidents at nuclear power stations is preferred to medical interventions.

Again, the major issue with an event at a nuclear plant is political, psychological, and economic—not medical. Terrorists can take over a plant, cut off its connection to the external grid, interfere with internal structure to cause a critical accident, or breach the containment by flying into a reactor. Security is a major concern. Are there adequate numbers of trained armed personnel at nuclear power plants, especially those in politically unstable regions? Some people seem concerned about the prospect of a commercial aircraft crashing into the containment dome of a nuclear power plant. This is unlikely in the United States, considering design specifications that typically plan for such events, as well as earthquakes of a reasonable magnitude. In earthquakes of extraordinary magnitude, the widespread destruction, fires, and loss of life makes the potential effects of a radiation release less worrisome.

Conclusion

There is increasing public concern regarding the medical consequences of exposure to ionizing radiations. And dealing effectively with these concerns requires diverse strategies, including policy decisions, public education, and, as a last resort, medical preparedness.