Forensic Toxicology in the Fore ... and Aft

From Forensic Magazine:

It could be the year 1850, or 1950, or 2008 … take your pick. It was a few days since the family dinner that the husband took ill. The nausea, vomiting, and diarrhea had been relentless. And that garlic taste in his mouth, it just wouldn’t go away. And finally, almost as a relief, he died. Whether as a relatively new bio-analytical science in 1850, or a discipline with remarkable, state-of-the-art equipment today, forensic toxicology has been asked to address concerns with such cases, to speak for the victimized husband, to tell the story of what caused his illness and death, and to provide the “smoking gun,” the identification of the arsenic that led to the wife’s conviction. Truth be told, however, things are never so clear.

Forensic toxicology is a scientific discipline with a split personality. While toxicology can be defined as the study of the adverse effects of chemicals on living things, the forensic component also mandates an analytical component.  Understanding the modern development of this duality sheds light on the impact of forensic toxicology on our criminal and civil justice systems and society.

Analytical Toxicology
The origin of modern analytical toxicology, and for that matter forensic toxicology, is often attributed to a Spanish physician named M.J.B. Orfila who actually practiced his vocation in France during the early to mid-1800s. Despite the establishment of laws against poisoning dating back to 81 B.C.E., it was his analysis of autopsy materials to identify poisons, and the subsequent accounting of such, that represented the first systematic approach to the identification of poisons. It was this approach that led to the first courtroom toxicological testimony by Orfila in 1840 during the trial of Marie Lafarge in France for poisoning her husband to death with arsenic.

If one focuses solely on arsenic, the evolution of bio-analytical forensic toxicology is easily made clear. Even prior to Orfila, a number of chemists worked on the identification of this widely used poison during that time period. Most of the developed tests surrounded the precipitation of arsenic through oxidative and reductive processes. Unfortunately, none of these tests proved sensitive enough for forensic toxicological purposes. However, in 1836, James Marsh, a British chemist, published an improved, sensitive method for the detection of arsenic. This method allowed for the physical presentation of the arsenic finding in a courtroom, and in fact, was the test used by Orfila in the Lafarge case. In 1842, Hugo Reinsch developed the namesake test that “plates” arsenic onto copper wire, turning it black. This was followed by Max Gutzheit’s semiquantitative test in 1879, again ultimately involving precipitation of arsenic. This latter test remained a hallmark in arsenic testing for almost 100 years. In the mid-1950s, Alan Walsh developed atomic absorption spectrometry. Within a decade or so after that, this instrumental technique was being readily used for a variety of elemental analyses, including arsenic. In the mid-1980s, ICP-MS (inductively coupled plasma-mass spectrometry) was made routinely available, a method recognized as the current standard in arsenic testing.

What the future holds for bio-analytical toxicology is anyone’s guess. If history holds true, and since mass spectrometric and other techniques are still maturing, it may be a little while before the next major fundamental analytical breakthroughs occur.

Toxicology
Toxicology is a biomedical science. The three main areas of toxicology – descriptive, mechanistic, and regulatory toxicology all advance our knowledge of basic biochemical and physiological processes, health and safety, and risk assessment. The descriptive branch of toxicology involves, as its name implies, the description of some phenomenon related to toxicology, whereas the mechanistic area attempts to determine what is at the root of the toxicological process, generally at the macro- and microlevels. The regulatory discipline applies the data from the descriptive and mechanistic arenas to develop various risk assessments for the sake of public safety. Forensic toxicology is considered a specialty field within toxicology.

Basic sub-disciplines within pharmacology and toxicology employed daily by the forensic toxicologist include pharmaco/toxicokinetics and pharmaco/toxicodynamics. Simply put, the former is what the body does to a drug or chemical, whereas the latter is what the drug or chemical does to the body.

Included in pharmaco/toxicokinetics is what is monikered, ADME, aka, Absorption, Distribution, Metabolism, and Elimination. These actions represent what the body can do to a drug or chemical once exposure has taken place. Pharmco/toxicodynamics describes drug or chemical actions that occur in the body once exposure takes place, and such actions range from no observable effect to death, and everything in-between.

In particular respect to forensic toxicology, the crux of the matter is always, “What do a set of analytical toxicological findings mean?” The answer to this, and other questions of forensic toxicological interest, cannot usually be based solely on analytical findings. It is the holistic nature of a case that allows for interpretation, with the accent on holistic. The more information that is available about a case or individual, the better the chance a forensic toxicologist can provide assistance. However, even when armed with knowledge about the case or individual, this does not guarantee forensic toxicological assistance in any given case. Today, the forensic toxicologist has to consider several ante- and postmortem phenomena, e.g., postmortem, or site-dependent, redistribution of substances after death, whereby drugs and chemicals can “move” from one site to another within the body after death; drug or chemical interactions, a phenomenon where one substance can interfere with the metabolism and elimination of another substance, thus leading to accumulation of the latter compound, and an increased risk of toxicity; pharmaco/toxicogenomics, where the same enzyme in the body responsible for metabolizing a particular compound may function too well or too poorly in any given person; etc. All of these, and other factors, sometimes make toxicological interpretation difficult, perilous, or impossible.

Undoubtedly, the future may provide greater and greater toxicological information, but it is not a certainty that this will add interpretive clarity for the forensic toxicologist. Pragmatically, since individual response, both kinetically and dynamically, will never be able to be fully accounted for, toxicological findings will always have some difference in interpretive value based on the practitioner.

SPECIFIC CHALLENGES IN FORENSIC TOXICOLOGY
First and foremost is being qualified to be a forensic toxicologist. The dual nature of the field make this particular challenge a long and arduous journey, certainly not meant for individuals seeking instant gratification. While there are many ways to become a practicing forensic toxicologist, there seems to be some basic commonality amongst such professionals. That is, basic educational requirements consisting of some combination of analytical chemistry and toxicology, often as separate educational endeavors, followed by mentoring and experience. Today, there are Board Certification programs for both the individual practitioner and the forensic toxicology laboratory. While offering no strict guarantees, appropriate certification generally demonstrates satisfactory compliance with the knowledge and principles necessary to function as both a forensic toxicologist and forensic toxicology laboratory.

As the challenges confronting the toxicological interpretation of findings have been previously discussed, a focus on the analytical challenges is also warranted. Forensic toxicologists don’t get a whole lot of say in the specimens they are asked to analyze, especially in the postmortem world. Specimens ranging from blood to urine to liver to brain to bone to hair all come with significant challenges based on the matrix composition. Add to that the state of the specimen, i.e., badly decomposed, covered with maggots, etc., and the challenges become even greater. While “tricks of the trade” are available to tackle such daunting specimens, sometimes such challenges cannot be overcome.

Further taxing the forensic toxicologist are the varied substances that may be of significance in any given case. Literally, forensic toxicologists must be able and capable to handle any of the forms of matter – solid, liquid, and gas. There are approximately 35 million or so chemical entities with registered names and probably multi-millions more in nature that have not been identified.

The last significant challenge for the forensic toxicologist, like all forensic scientists, is the courtroom. It is a world that, no matter how long one has practiced, remains foreign. Unlike many other forensic disciplines, the analytical findings are not the sine qua non of the testimony. Most commonly, it is the opinion of the forensic toxicologist that is sought, the very thing that elicits the best in the adversarial nature of attorneys.

Posted: 6/16/2008 10:18:00 AM

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Forensic toxicology is the use of toxicology and other disciplines such as analytical chemistry, pharmacology and clinical chemistry to aid medical or legal investigation of death, poisoning, and drug use. The primary concern for forensic toxicology is not the legal outcome of the toxicological investigation or the technology utilised, but rather the obtaining and interpreting of the results

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