A Critique of Brain Wound Research, Part 1
Christopher D. Smith, M.D.
December 17, 1988
Comments on 'The effect of an experimental missile wound to the brain on brain electrolytes, regional cerebral blood flow, and blood brain barrier permeability" (Contract # DAD17-83-C-3145) and "Experimental studies on a brain missile wound: ascertaining pathophysiology and evaluating treatments to lower mortality and morbidity" (0MB #3090-0116) by Michael E. Carey, M.D.
The first document is a declassified "annual report" issued by Dr. Carey, summarizing research from 1983 to 1985. The second is an astonishing proposal which asks the federal government to fund $1,777,999.00 for the study of experimental brain injury in cats. I believe that public monies are grossly misspent in this research. I have several basic objections to Dr. Carey's project:
1. The Study is Based on Fundamental Misconceptions
The study assumes that the damage done by a projectile is proportional to its kinetic energy. This simplistic assumption (which I refer to as the "Field and Stream" theory, after the type of magazine which popularized it) has been convincingly refuted.1
According to the Field and Stream theory, a 500 gram egg and a 500 gram brick, having the same kinetic energy, should produce exactly the same damage when dropped off a building onto the human head. In fact, the damage produced by a projectile is almost exclusively determined (in the context of modern warfare) by the design and construction of the projectile, not its kinetic energy. This is the reason, for example, that the Soviet AK 47 was such a superior weapon in Viet Nam. "It cannot be overemphasized that dogmatically basing treatment recommendations on velocity or energy level of the bullet is inappropriate. Too many factors influence the bullet-tissue interaction for any formula to be able to predict the severity of injury."2 Thus, Dr. Carey's research is based on a simplistic and incorrect model of projectile brain injury.
2. Brain Injury in Cats does not Duplicate Brain Injury in Humans
Even if the Field and Stream theory applied to projectile brain damage, Dr. Carey self-destructs his own study by using a projectile which is "8-16 times too heavy" compared to the average battlefield missile (p.85 of the grant proposal).
Dr. Carey believes that there is a "scaling factor" between the 1300 gram human brain and the 25 gram cat brain. In order to model human brain injury in cats, he believes that the projectile should be 25/1300 lighter than the average 0.1-0.2 gram Viet Nam projectile. Due to technical limitations, the smallest sphere that can be practically fired weighs 0.03 grams. The experimental projectile is thus 8-16 times heavier than the average projectile striking a soldier in battle. This is scarcely an accurate model.
Dr. Carey's "scaling factor" is itself a fundamental error. While it is true the cat brain is smaller than the human brain, the cells making up the cat brain are the same size as the cells making up the human brain. The human brain weighs more because it contains more cells. The research proposed by Dr. Carey concerns the effects of cellular disruption in the living brain. However, the missiles he fires into cat brains are 3-7 times lighter than the average Viet Nam projectile. Consequently, depending on one's point of view, the projectiles used in Dr. Carey's research are either 8-16 times too heavy or 3-7 times too light to be an accurate model of human brain injury in the battlefield.
There are a number of other problems with using cats to model human brain injury. The anatomy of the cat brain is, of course, significantly different from the human. Results are limited by these species differences, making direct application to humans impossible. Dr. Carey himself thinks that the use of cats is "a compromise between animal size, brain size and configuration, and missile size" (p 85 of the proposal). The problem with this "compromise" is that it invalidates any direct application to humans.
Moreover, Dr. Carey commits another methodological error by immobilizing his cats in stereotaxic frames prior to shooting them. It is generally accepted that rotational or shear forces are major determinants of brain injury in human head trauma. By immobilizing his cats, Dr. Carey creates an artificial situation which has no counterpart in real life.
3. The Study Ignores Existing Research
During the Civil War, military surgeons fired bullets into cadavers in order to investigate the effects of various projectile designs. Incredibly (and I say this as a taxpayer), little progress has been made since then. One would think that the military establishment, having access to virtually unlimited funds and clinical material, would have made some progress in the study and treatment of missile wounds.
Although Dr. Carey has not published a single paper on the subject, he expects to make huge contributions to brain wound knowledge. He claims that his research will, "within a few years, bring the level of understanding of brain missile wounds up to that of cerebrovascular accidents or closed head injuries which have been intensively studied for decades" (p. 5 of the proposal).
Dr. Carey's proposal promises to address an incredibly broad range of topics. He will single-handedly study:
-- Morbidity and mortality on the battlefield
-- The acute physiological consequences of brain injury
-- Gross and microscopic anatomy in brain-injured subjects
-- The long-term pathophysiological consequences of brain damage
-- The pathophysiology of hemorrhagic shock
-- The effects of cerebral trauma on regional cerebral energy metabolism, blood and brain metabolites and serum osmolality
-- Neurotransmitter systems and prostaglandins
-- The interactions between focal brain damage and brainstem function
-- The effects of trauma on regional cerebral blood flow and the blood-brain barrier
-- The effects of arterial oxygen saturation and pCO2
-- Physiological and neurochemical parameters in animals kept alive after experimental brain damage
-- Behavioral consequences, both short-term and long-term, in brain-damaged animals
-- EEG consequences of brain damage, including the effects of drugs on neural function
-- Biomedical imaging systems
-- The effects of various treatments, including twelve different drugs, on morbidity and mortality, including "pretreatment" of subjects who are about to be brain damaged
-- Adjunctive medical therapy to sustain and improve brain function following a missile wound
All of this will be done in a 30 X 45 foot laboratory at LSU Medical Center. Dr Carey assures us that his studies "should quickly lead to sound physiologic and pharmacologic methods to ameliorate brain damage caused by missiles" (p. 3 of the proposal). Although researchers in major medical centers throughout the world are already working on these problems, Dr. Carey confidently announces that he will find all the answers.
In summary, I am appalled by this "research" at taxpayers expense. It is poorly conceived and medically unsound. This grandiose and self-serving proposal would be a most inefficient use of public funds.
1. Fackler, M.L.: Wound Ballistics: A Review of Common Misconceptions. JAMA 1988;259:2730-2736.
2. Culp, J.S.: JAMA 1988;260:3279.
A Critique of Brain Wound Research, Part 2
March 10, 1989
Comments on "An experimental brain missile wound: Ascertaining pathophysiology and evaluating treatments to lower mortality and morbidity. Annual report 14 April 1986 through 13 April 1987"
This report summarizes research conducted at a cost to the taxpayer of approximately $1,800,000.00 in which 23 cats were killed in what is purported to be a laboratory simulation of battlefield missile wounds to the brain. I have argued previously that this model is conceptually and methodologically flawed, and therefore is unlikely to generate data which could be used to guide treatment in humans.
The experiment represents a considerable scaling-back of the original 1985 proposal which promised "within a few years" to bring our understanding of missile wounds up to the level of "cerebrovascular accidents or closed head injuries which have been studied intensively for decades." So far, the research program has brought our understanding up to the year 1868, when Harlow published the case of Phineas Gage, a foreman who survived an injury in which a crowbar was driven by a dynamite explosion through his frontal lobes. Gage survived with no neurologic deficit except personality changes.
A more recent example from my own practice was an 18 year old male who presented to the emergency department complaining of a scalp laceration. He said he had been playing in the kitchen with his friends, one of whom had accidentally pushed him, causing him to fall backwards and hit his head on the kitchen sink. X-rays of this young man, who was completely intact on neurologic examination, showed a penetrating gunshot wound to the brain, with bullet and bone fragments scattered along a track extending from the occipital to the frontal pole of the cranial vault. Confronted with the X-ray, the patient admitted that he and his friends had been playing with a .25 caliber revolver, which had accidentally discharged.
The point is that it is possible (although certainly not common) to sustain penetrating brain injury without global neurologic damage or even transient neurologic deficit. This in turn implies that cerebral blood flow is not necessarily disrupted in regions of the brain distant to a penetrating missile track.
One hundred and nineteen years after Harlow's report, the wound research lab at Louisiana State University has confirmed this fact in cats, at a cost to the taxpayer approaching two million dollars. I consider it extremely unlikely that the experiments at LSU will generate information which will be of any use in the treatment of penetrating missile wounds in humans.
First, the experimental set-up is non-physiologic: cats are immobilized in stereotactic frames; the anterior wall of the right frontal sinus is removed prior to injury; spherical missiles (which, as I pointed out previously, are not similar to real bullets, and are either too light or too heavy, depending on one's point of view, to accurately model human bullet wounds) are fired on predetermined trajectories (preselecting a part of the brain which is known to be relatively resistant to missile damage); cats are anesthetized and paralyzed with drugs which have effects on cerebral metabolism. Secondly, the experimental method is flawed: the experimenters shoot cats, perform measurements on cerebral blood flow, and then arbitrarily select the best 14 out of 23 sets of data for further analysis. This methodology is unacceptable. You either have a reproducible model of missile brain damage or you don't. The experimenters do not have a reproducible model.
In my opinion, the LSU experiments should be terminated immediately. The research is nonproductive (the group has yet to produce a single scientific paper) and ridiculously expensive. Moreover, the conceptual and methodological basis of these experiments is seriously flawed. Government funding of such research represents a waste of the taxpayer's money.