THE WAR IN AFGHANISTAN | NEWSFOCUS

From soldier to subject. Researchers are collecting data from casualties like this one in Afghanistan. Downloaded from http://science.sciencemag.org/

personnel, they come with exhaustive data

relating to preinjury health and postinjury on October 16, 2017 War as a Laboratory outcome. Many of the insights gained from battlefi eld studies have found their way into For Trauma Research civilian emergency medicine. But war is also the most chaotic and stressful environment The military is sending scientists onto the battlefi eld to fi nd ways to improve imaginable for doing science. “Someone has emergency medicine, but the research faces a practical and ethical minefi eld to take down all this data,” Osborne says. “I saw this poor girl trying to turn this blood- KANDAHAR AIRFIELD, AFGHANISTAN— question.” What saved him was a series of smeared page, trying to get data off of it. … Easing back into a borrowed chair in a tiny extremely rapid interventions, including new That’s the reality. Until you’ve lived that, you trailer office here on the base, Cmdr. Lisa techniques for applying tourniquets, drugs, don’t realize how diffi cult it is.” Osborne should be enjoying a moment of and blood products. Those insights came Adding to the diffi culty, controversy has calm. But all she can talk about is work. “I saw from medical research conducted in Iraq and dogged JC2RT projects, including charges a guy show up here in trauma. You wouldn’t Afghanistan, orchestrated through a U.S. mili- by journalists that researchers rushed experi- believe the condition he was in,” she says, tary program called the Joint Combat Casu- mental treatments onto the battlefi eld without recalling the victim of an improvised explo- alty Research Team (JC2RT). As its deputy proper ethical review or suffi cient safety test- sive device (IED). The extent of the director, Osborne runs the show. ing, needlessly risking the lives of soldiers. was shocking, even to the hardened medics In many ways, war is the perfect labora- Science investigated these issues with the help working here in Afghanistan. “He was miss- tory for trauma medicine research. On any of two bioethicists and several sources from ing both legs and his whole backside. But he given day, dozens or even hundreds of casu- both civilian and military trauma medicine. was alive, breathing on his own.” alties arrive by helicopter to military hospi- For most people, a scene like that would tals across Afghanistan. IEDs are the num- Exploring the fill them with nothing but horror. But for ber one risk, often combining burns, deep From the moment a bullet or piece of shrap- Osborne, a U.S. Navy anesthesiologist and lacerations from shrapnel, and brain trauma nel hits the body, the clock is ticking. Trauma medical researcher, it was a reminder of from blast waves. Injuries like these are too medics call it the “golden hour,” the small hard-earned progress. “Years ago, that kind rare to study in peacetime. And because window of time in which the patient’s life

CREDIT: AP CREDIT: of patient would be dead,” she says. “No all the patients in these studies are military can be saved. Death can come in a mat-

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ter of minutes, hours, or days, but the most components—plasma containing platelets crucial interventions must be made imme- and clotting factors—added sparingly later. diately. War has been “an amazing learning “What we realized,” says Osborne, “is that environment,” says Osborne, with each con- if you wait on those clotting factors, then fl ict pushing trauma medicine forward. New you’re always behind. You can keep putting motorized ambulances in World War I saved in red blood cells and they just keep pouring wounded soldiers by getting them from the right out [of the wounds].” The transfusion front lines to the hospitals quickly. World protocol for severe injuries has now been War II saw the fi rst large-scale use of anti- revamped based on JC2RT research. For biotics. Medics in the Korean War pioneered injuries that require massive transfusions, repair and grafting techniques for vascular the equivalent of whole blood is now given surgery. In the Vietnam War, portable radi- immediately, including a full complement of ology equipment and ventilators were tested clotting factors. The researchers found that it in the fi eld. reduced mortality rates in these patients from With the wars in Afghanistan and Iraq, 65% to 17%. combat medicine has faced a new prob- Another dramatic change from JC2RT lem. “The diffi culty for the current genera- research is how “damage control” surgery is tion is getting approval for research,” says performed. “We found that it’s critical that we

Col. Martin Bricknell, a senior doctor in the Whole blood. These empty transfusion bags from not close some injuries when they come in Downloaded from U.K. Royal Army Medical Corps who hosted a single patient in Afghanistan show the 1-to-1 here,” Osborne says, “because the outcomes this reporter’s visit to military facilities in ratio of blood products now used. are massive infections and sepsis.” Instead, Kandahar (see p. 1256). “It is considerably blood vessels are tied off and the wound is left more rigorous than it used to be, and there- Once a research project passes this pre- open, sometimes for several days, vigorously fore the lag between good idea to outcomes is screening, it must be approved by an inde- cleaning it with saline. “We used to close that

much greater.” JC2RT was created in 2006 to pendent U.S. Army institutional review board wound 7 years ago,” she says. http://science.sciencemag.org/ streamline that process. (IRB) based at Fort Detrick, Maryland. That Other problems have yet to be solved. “We’re a team of eight,” says Osborne, review process is identical to those at any One of the most urgent is compartment syn- a petite, blonde 42-year-old in the middle research institution, Osborne says, sourc- drome, the accumulation of fl uid between of her 6-month tour of duty in Afghanistan. ing outside experts as needed. Osborne and tissue layers that can result in When she is not at war, Osborne is the direc- her colleagues identify issues likely to cause or even death if the pressure cuts off blood tor of anesthesiology research at the Uni- problems with reviewers, giving researchers to organs. One JC2RT project is testing formed Services University of the Health a chance to address them early “so that when whether the pressure in an injured limb can Sciences in Bethesda, Maryland. “Most of [the proposal] goes to IRB it has a chance,” be diagnosed earlier by detecting a drop in us have Ph.D.s,” she says, “but we’re not data Osborne says. At least one of the investigators oxygen in the tissue. Another unsolved prob-

collectors.” Instead, JC2RT is a gatekeeper must be present to undertake the study in the lem explored by JC2RT projects is how to on October 16, 2017 and overseer. Ideas for projects are put for- fi eld. “Most of these folks, they’re only here diagnose brain trauma, for example, using ward by researchers from all branches of the for a short amount of time. If their stuff gets ultrasound to measure the blood pressure of U.S. military, often with university-based held up in IRB for 6 months, they miss the vessels within the eye. scientifi c partners. As the proposals roll in, boat. We try to prevent that from happening. Because of the streamlined process, Osborne says, “I’m the one who has to give But it does happen.” insights from those projects will move quickly people the bad news that their research proj- To date, about 100 projects have made it onto the battlefi eld. In medical research, says ect isn’t going to work.” through this gauntlet and into the fi eld, so far Osborne, “you normally have a 10-year pipe- A typical problem is feasibility. “The producing dozens of peer-reviewed research line” between the fi rst experiment and a new people who are writing these [proposals] papers (see table on p. 1263). All of them take treatment for patients. “For us, it can be half are just coming into theater,” Osborne says. advantage of data from the U.S. military’s a year,” she says. “They don’t realize that there’s no way they’re Joint Theater Trauma Registry (JTTR), a The speedy turnaround has doubtless going to be able to do it.” As an example, she continuously updated record of trauma cases saved lives. But at the same time, it has describes a project that would have required in Iraq and Afghanistan. JTTR currently con- invited intense scrutiny. infrared photography of injured soldiers’ tains the case histories of 40,000 patients, limbs. “You often have a whole sea of people including medical observations, treatments, Serious charges working on the patient. You can’t tell them, and outcomes in minute detail. Most of the Wartime medical research has a troubled his- ‘Okay, everybody step back. I’m going to research has yielded incremental improve- tory. The most notorious examples are the snap some photos.’ ” ments to existing treatments. But some have experiments performed on prisoners by Ger- Another fatal fl aw is the use of experi- overturned paradigms of trauma care, says man and Japanese doctors during World War mental medical devices. “It’s a deal-breaker,” Osborne. One example is blood transfusion. II. As a 2002 directive by the U.S. Department Osborne says, because of U.S. federal regu- Some battlefield injuries are so severe of Defense states, “The involvement of pris- lations. “If you use them, you must have that patients require massive transfusions, oners of war as human subjects of research is informed consent from the patient. Period.” sometimes as much as fi ve times the volume prohibited.” So even harmless experiments Most wounded soldiers plucked from the of blood in the body. The standard transfusion on detainees are forbidden by JC2RT, says battlefi eld are in no state to grant consent for a practice begins with concentrated red blood Osborne. Nonetheless, its research projects

new device, even if they are conscious. cells in a saline solution, with the other blood have attracted their share of controversy. CREDITS: ISAF

1262 11 MARCH 2011 VOL 331 SCIENCE www.sciencemag.org Published by AAAS THE WAR IN AFGHANISTAN | NEWSFOCUS

Trauma Research on the Battlefield But the criticism is not surprising. “There is scarcely a disease or treatment in the world Research topic Summary Example of output or project status without strong disagreement among knowl- Damage control Methods for resuscitating patients M. A. Borgman et al., The ratio of blood edgeable people about the best approach,” resuscitation with massive blood loss products transfused affects mortality in Fost says. As for the charge of lax ethical patients receiving massive transfusions at a combat support hospital. J Trauma review, Fost found the opposite to be true. 63, 805 (2007). “There was a continuous dedication to eval- uating practices in a way that many civil- Compartment syndrome Using oxygen concentration and other Ongoing ian medical centers would envy,” he says. markers to detect dangerous fluid buildup in injured limbs Beyond the standard IRB approval process, new treatments are evaluated in real time Prehospital lifesaving Assessing the performance of Ongoing with weekly “morbidity and mortality con- interventions immediate interventions in trauma care ferences” that include military physicians from around the world. They are part of a Vascular surgery Comparing the effectiveness of vascular S. M. Gifford et al., Effect of temporary treatment for wounded soldiers shunting on extremity vascular injury: an “serious quality-improvement program,” outcome analysis from the Global War Fost says, which is “beyond anything I’m on Terror vascular injury initiative. J Vasc Surg 50, 549 (2009). familiar with in civilian medicine.” Wikler agrees that there is no clear evi-

Traumatic brain injury Biomarkers and quantitative EEG for Ongoing dence of wrongdoing but adds that the extra Downloaded from detecting brain injury and scrutiny is justifi ed. “There is a long tradition characterizing immunodeficiency of using soldiers as guinea pigs for research,” Critical Care Air Transport Analysis of resuscitation and early M. D. Goodman et al., Traumatic brain he says. “And trauma medicine research in Team (CCATT) clinical outcomes as a function of injury and aeromedical evacuation: general has the problem of a lack of consent aeromedical platform when is the brain fit to fly? J Surg Res 164, 286 (2010). from unconscious patients,” which raises the

bar on what types of experiments are permis- http://science.sciencemag.org/ Combat medicine training Assessing the effectiveness of J. A. Tyler et al., Current US military sible. JC2RT research “falls into this dou- medical training in the context of operations and implications for military ble shadow,” Wikler says. “But that doesn’t Iraq and Afghanistan surgical training. J Am Coll Surg 211, 658 (2010). mean it was wrong.” “The moral of this story is that continu- Tourniquets Optimizing the use of tourniquets J. F. Kragh Jr. et al., Survival with ous research is not only desirable but ought for improving survival and reducing emergency tourniquet use to stop to be seen as obligatory, barring insuper- in major limb trauma. Annals of Surgery 249, 1 (2009). able ethical barriers,” Wikler says. “All of us hope that if we are injured in a traffi c Soft tissue injury Assessing the effectiveness of the R. Fang et al., Feasibility of negative accident and are brought to a hospital, the vacuum assisted device and other pressure wound therapy during

innovative treatments for soft tissue intercontinental aeromedical evacuation ER docs won’t be using primitive medical on October 16, 2017 69 damage of combat casualties. J Trauma , S140 techniques because research on banged-up (2010). patients was forbidden.” Explosive mass casualty Developing guidelines for intensive B. W. Propper et al., Surgical response to This is also the view of Peggy Knud- care for multiple casualties caused multiple casualty incidents following son, a trauma surgeon and researcher at the by explosions single explosive events. Annals of Surgery 250, 311 (2009). University of California, San Francisco, who has trained U.S. military doctors in Iraq and has advised the military on JC2RT research. A 2009 investigative report by The Balti- consin, Madison, to assess the issues raised Knudson says some of the treatments tested more Sun, which has been widely circulated by the article and, more generally, JC2RT’s in Iraq and Afghanistan are already being among civilian and military doctors, alleged procedures for ensuring that battlefield applied in civilian hospitals in the United that researchers sidestepped standard ethi- research is carried out ethically. Fost, who is States. “I copied the military burn proto- cal practices in Iraq and Afghanistan. “The the architect of the current standard ethical col and brought it back to my [hospital],” military exposed hundreds of soldiers and procedures for trauma medicine research, she says. She was also impressed by the Marines to the risks of unproven treatments pulled in several other experts. “I talked at new methods for applying tourniquets and that were unlikely to do much good,” the length with four experienced surgeons, three temporarily shunting blood vessels. “I use report claims. U.S. Air Force Lt. Col. Todd of whom specialize in trauma and have mili- them both.” She says that the military’s mas- Rasmussen, deputy commander of the U.S. tary experience, two of whom have served sive blood-transfusion protocol is being Army Institute of Surgical Research in multiple tours in Iraq and/or Afghanistan,” tested at 11 civilian trauma centers across San Antonio, Texas, who oversees JC2RT, he says. He also reviewed numerous articles the United States. declined to comment, saying only that the in peer-reviewed journals and U.S. Food Here in Afghanistan, Osborne has to get article refl ected “vigorous but appropriate and Drug Administration documents. Both back to work supervising the research proj- academic deliberations” within the medical bioethicists posed questions about JC2RT ects. “I can’t wait for tomorrow,” she says. research community. research directly to Osborne through a series Once per week, she stops being a scientist Science asked two bioethicists, Daniel of e-mail exchanges. and becomes a doctor, waiting for the injured Wikler of Harvard Medical School in Boston Fost’s conclusion: None of the examples to arrive from all directions.

SOURCE: JC2RT and Norman Fost of the University of Wis- of unethical research held up under scrutiny. –JOHN BOHANNON

www.sciencemag.org SCIENCE VOL 331 11 MARCH 2011 1263 Published by AAAS War as a Laboratory For Trauma Research John Bohannon

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