The Other Side of Despair

Queen Victoria was not at all amused:  “We do not believe that anyone could be insane who wanted to murder a Conservative Prime Minister.”  The target of a number of assassination attempts herself, she was upset enough upon hearing the verdict in the trial of Daniel M’Naghten that she complained to the Prime Minister, prompting the House of Lords to revive an ancient right to intervene by directing the Supreme Court of Judicature to respond to five questions about the case. 

M’Naghten was a Scottish woodcutter who acted on delusions that he was being persecuted by the Conservatives by attempting to murder tory Prime Minister Robert Peel:  “The Tories have … compelled me to do this.  They follow, persecute me wherever I go, and have entirely destroyed my peace of mind ….” 

Setting aside the queen’s implication about the political affiliation of the victim, the facts are well known.  M’Naghten had exhibited symptoms of mental illness for at least a couple of years, his landlady reporting that he believed there were devils in human form seeking to kill him.  Those devils evidently enjoyed the form of conservative politicians because some time later, he applied to the London Police for protection from the Tory persecutors who sought his life.  On January 20, 1843, a few days after being seen loitering suspiciously near Whitehall, he mistook Edward Drummond for Peel, walked up to him in broad daylight, drew his gun, and shot him in the back.  When brought for trial and asked for his plea, he asserted that he was “driven to desperation by persecution” and that he was “guilty of firing.”  After testimony by a number of witnesses, including physicians who testified that M’Naghten’s delusions deprived him of control over his actions, he was found not guilty on the ground of insanity. 

For many years, the M’Naghten test defined the circumstances under which a defendant could succeed in using insanity as a defense to a crime.  The test developed in response to the five questions put to the Court of Judicature by the House of Lords:  a person is not guilty if, at the time of the person’s actions, he either did not know the nature or quality of his actions or did not know what he was doing was wrong.  In modern parlance, there are two tests, either of which may be sufficient for an insanity defense to succeed:  the “cognitive capacity” test and the “moral capacity” test.  But it is the response to the fifth question in particular that interests me today, in which the Court noted the impracticality of deciding the legal question of insanity with science alone; instead, “each of those questions involves the determination of the truth of the facts deposed to, which it is for the jury to decide, and the questions are not mere questions upon a matter of science.”  The record of the case can be found here.  

As Jared Loughner entered a plea of not guilty on Monday after opening fire in Tucson earlier this month, killing a federal judge and seriously injuring a member of Congress, many have questioned to what extent an insanity defense might apply.  The parallels with the M’Naghten case are difficult to avoid:  Loughner appears to have been suffering from a number of delusions, and irrationally focuses responsibility for his ills on the U.S. government.  What is perhaps most surprising, though, is how little the view about the role of psychiatric science in bearing on the question of insanity has changed in 150 years.  After all, the last few years have seen tremendous advances in understanding the structure of the human brain and the physiological relationship with many mental illnesses:  the technique of functional MRI allows specific brain structures to be associated with different activities, different thoughts, different senses, etc. 

Coincidentally, it was the State of Arizona’s insanity test that was the subject of the U.S. Supreme Court’s most recent ruling on the defense, the same state where Loughner went on his rampage.  While Arizona had historically codified the full  M’Naghten test, with both the cognitive-capacity and moral-capacity prongs, it dropped the cognitive-capacity test in 1993 so that a defendant must lack moral capacity for an insanity argument to succeed.  There is a great deal of discussion of different issues related to insanity in the Court’s opinion in Clark v. Arizona (which can be read here), but of particular interest is its general distrust of evidence related to mental disease — and acceptance of Arizona’s restrictions on considering such evidence — even as recently as 2006: 

[T]he diagnosis may mask vigorous debate within the profession….  [T]his professional ferment is a general caution in treating psychological classifications as predicates for excusing otherwise criminal behavior….      [T]here is the potential of mental-disease evidence to mislead jurors … through the power of this kind of evidence to suggest that a defendant suffering from a recognized mental disease lacks cognitive, moral, volitional, or other capacity, when that may not be a sound conclusion at all….  These dangers arise because of the imperfect fit between the questions of ultimate concern to law and the information contained in a clinical diagnosis.

 The Court’s conclusion that a psychiatrist has no more particularly relevant knowledge on the legal and moral issues related to an insanity defense than does a layman has, unsurprisingly, been subject to significant criticism in psychiatric circles.  The American Psychiatric Association and the American Psychological Association have both taken the position, seemingly reasonable, that those who study the human brain are in a position to offer expert evidence about how the functioning of the brain can lead individuals to take actions that we all consider horrific.  A copy of their joint amicus brief in Clark can be read here.  Indeed, it seems more that there is a widespread misunderstanding of mental disease that could be demystified through expert testimony rather than the Court’s view that such testimony may have the effect of clouding the issues and misleading jurors.  Disagreement among experts is nothing new:  juries are called upon all the time to evaluate disagreements, even among experts, so they can reach decisions in cases that are in some sense “fair.” 

Contrary to widespread conception, insanity defenses are only rarely raised and even more rarely succeed.  By all accounts, it appears that Loughner did indeed possess moral capacity when he opened fire, even if he was suffering from certain delusions:  his statements on his Myspace page and his quick statement to “plead the Fifth” when he was arrested demonstrate a knowledge that he well understood what he did was wrong.  I suspect that an insanity defense, if raised, will fail.  But at the same time, as someone who generally believes that we make better decisions when we have more information rather than less, I’m uncomfortable with limiting the evidence of mental illness that a jury can consider when evaluating that defense.

Its Truth Only Partially Known

It was while Samuel Hahnemann was translating a book by William Cullen in 1789 that he encountered a description of how Peruvian bark could be used in treating malaria.  In his book, Cullen attributed the effectiveness of the bark to its bitter and astringent properties.  Only 24 years old at the time, Hahnemann impetuously added a footnote to the translation disagreeing with the explanation and noting that there were other substances even more bitter and astringent that Peruvian bark that were were ineffective against malaria.  Instead, Hahnemann drew from his own experience taking toxic doses of the herb, conscious of how his body responded with fever and chills that he found similar to the symptoms of malaria. 

It was thus that Hahnemann developed the “law of similars” that is embraced by homeopaths, the word “homeopathy” being a combination of the Greek words “homoios” (“similar”) and “pathos” (“suffering”).  The idea was that disease could be prevented by using a substance to cause the body to react in a way that was similar to its reaction to disease.  While homeopathy is not accepted by modern medical science, the idea was not particularly outlandish considering the state of medical understanding at the time.  It was, after all, around the same time that Edward Jenner discovered that smallpox could be prevented by deliberating infecting people with small doses of cowpox to produce symptoms similar to those of smallpox.  I described some of the history of that development of vaccination here

Because the substances used to induce certain conditions were toxic and potentially dangerous, Hahnemann proposed to use extreme dilutions, so much so that none of the original substance would remain.  He proposed dilutions of 30C, meaning that the substances were to be diluted by a factor of 100, with the dilution repeated 30 times.  His proposed dilution is accordingly 10-60, a dilution so severe that it would be necessary to consume a liquid remedy that is roughly 10 billion times the volume of the Earth in order to consume a single molecule of the substance.  The dilution is so great that the effectiveness of homeopathic remedies is often attributed to the placebo effect. 

While homeopathic medicine had a considerable following through much of the 19th century, it was ultimately displaced by the development of modern medicine around the beginning of the 20th century.  Prompted primarily by concerns about the potential toxicity and side effects of now-conventional medicines, homeopathy began a resurgence sometime in the late 1970’s or early 1980’s.  There are virtually no adverse side effects with homeopathic treatments because the active ingredients have been so diluted as not even to be present, and this is one of its main attractions.

But some companies have wished to have their cake and to eat it to.  The cold remedy Zicam, taken as a nasal spray, is a notable case in point.  Marketed as a homeopathic remedy, it is prepared with highly diluted galphimia glauca, histamine dihydrochloride, luffa operculata, and sulfur.  It also includes only modestly diluted zinc acetate at a dilution of 2X, i.e. 1/100th dilution, and zinc gluconate at a dilution of 1X, i.e. 1/10th dilution.  These zinc compounds are at a level where they may still be biologically active, suggesting that the remedy is intentionally prepared so that it may be marketed as a safe homeopathic remedy while also including a biologically effective solution of 10% zinc gluconate. 

In 1999, a small number of physicians began noting that some of their patients developed anosmia — loss of the sense of smell — after consuming Zicam.  Familiar with studies dating from at least the 1930’s associating intranasal application of zinc sulfate with anosmia, those physicians questioned whether there was sufficient zinc compound in the remedy to be causing anosmia in patients.  There have been a number of reports suggesting an association, but the numbers are small — small enough that the manufacturer maintains they are not statistically significant while noting that there are many causes for anosmia.  It is fair to say that it remains unclear whether the zinc compounds in Zicam are responsible. 

Last week, the Supreme Court of the United States heard oral arguments in the case of Matrixx Initiatives v. Siracusano.  At issue is whether Matrixx, the manufacturer of Zicam, had a duty to report the concerns over a causal relationship between Zicam use and anosmia to investors.  Even if public response is based on an unsubstantiated link, there is still an impact on sales of the product and on the value of an investment in the company. 

The issue is not an easy one, but it is easy to see both sides of the argument.  On the one hand, a company should not need to respond to every unsubstantiated allegation, rushing to inform investors that it has irrationally been accused of something.  But conversely, this is a case where the concerns — even if perhaps not well nailed down statistically — are being raised by legitimate physicians on the basis of past, relevant research.  A transcript of the entire oral argument can be read here.

How the Court will ultimately decide the case is unclear because the facts are not clear-cut.  But the principles it will use are well-defined.  Companies are liable if they fail to disclose information that is considered “material” in that it will affect the value of the product and if they have failed to disclose that information with an intent to mislead.  Regardless whether the value that many consumers find in homeopathic remedies is substantiated, they deserve, as always, to have accurate information about what they are consuming.

To the End of Reckoning

It is not a shining moment for science or for law. 

Indeed, the story reads more like a gripping thriller — one that the reader finally sets down by the side of the bed at 3 AM thinking that it was an exciting enough tale to forgo sleep even if it was totally unbelievable.  Imagine the plot summary.  A physician, receiving handsome payments from an attorney who wants to bring a class-action suit against a vaccine manufacturer, invents a fictional disorder and fabricates data to establish a fraudulent link with the vaccine.  The stuff of Ian Fleming or John Le Carre. 

In 1998, Andrew Wakefield and twelve other others published a paper in Lancet, a prestigious medical journal, implying a link between the measles, mumps, and rubella (“MMR”) vaccine and a new syndrome of autism and bowel disease.  Many scientists were skeptical, pointing to any number of scientific weaknesses in what was reported.  But large segments of the public relied on the paper when its findings were reported in the general press.  Vaccination rates plummeted as parents determined that the risk of autism in their children was too great.  The inoculation rate dropped most dramatically in Britain, from about 92% to below 80%, but many children in other parts of the world also failed to receive the MMR vaccine as a direct consequence of the Wakefield paper.  From having been declared “under control” in the mid 1990’s in Britain, measles was declared “endemic” in Britain only ten years after publication.  The U.S. Centers for Disease Control notes that more cases of measles were reported in the United States in 2008 than in any year since before publication, with more that 90% of those having not been vaccinated (or having a vaccination status that was unknown). 

A series of articles being published in the British Medical Journal  began last week, exposing a fraud surrounding the paper that author Brian Deer likens to the Piltdown Man scandal, an elaborate hoax that disrupted the natural course of paleontology research and that took decades to uncover.  I briefly discussed Piltdown man some months ago here.   Deer describes how Wakefield was retained by attorney Richard Barr two years before the paper was published, and paid more than £435,000, six times his annual salary as a physician.  The children in the “study” that he conducted on MMR were targeted and preselected to have desired symptoms, he reinterpreted clinical records to suit his contrived syndrome, and “chiseled” histories to reach unsupported clinical diagnoses.  While admonishing many who failed to exercise sufficient diligence — coauthors, fellow scientists, hospital managers, journal editors — Deer reports that the evidence shows it was Wakefield alone who perpetrated the scandal and that not even the attorney who paid him knew what he was doing. 

When Deer first reported on irregularities surrounding the study in 2004, ten of Wakefield’s coauthors retracted the interpretation.  In January 2010, a five-member tribunal of the British General Medical Council found dozens of allegations of misconduct proved, including four counts of dishonesty and twelve involving the abuse of developmentally challenged children.  A copy of the results of the Fitness to Practise Hearing, which was the longest ever conducted by the Council, can be found here.  

The consequences of the misconduct are truly staggering.  Epidemiological studies were conducted at great public expense, unable to confirm any link between autism and the MMR vaccine.  Research funds and personnel were diverted from more legitimate avenues to understand the actual causes of autism and to help those affected by it.  Many children who might otherwise have been vaccinated suffered an illness that we have the technology to prevent and may be among the small number who died as a result of having contracted measles.  At the moment, the effect on mumps contraction remains unclear because its peak prevalence is in older adolescents. 

In its editorial, the British Medical Journal pulls no punches.  It asks whether it is possible that Wakefield was wrong but not dishonest.  After all, scientists are allowed to be wrong.  Indeed, it is a strength of the scientific method that all honest ideas should be considered so that they can be scrutinized and dismissed if they are incorrect. 

The answer it gives is a simple one:  “No.” 

Not a single one of the case studies was reported accurately.  The pattern of the misreporting shows an intent to mislead.  Already actions are being taken to examine Wakefield’s other publications, mindful of the experience that misconduct is rarely an isolated event. 

When I write about various issues on this blog, one of the things that I am reminded of repeatedly are the similar ethical requirements that attorneys and scientists are expected to adhere to.  Those ethical requirements exist because of the importance of the work that they do, and the trust that is necessarily placed in them by the public. 

Attorneys suffer a great deal from distrust by the public, and I have always thought that that is one of the prices to be paid for the system.  Attorneys deal with controversies between parties that have opposing interests and operate in a system that requires that the best arguments be put forward on behalf of their clients, most especially for those clients who seem unlikeable and potentially subject to victimization if the state or other opposing party is not held to the strictest standards of proof. 

Scientists have generally enjoyed a more favorable reputation by the public, but misconduct of this scale has repercussions that extend far beyond even vaccines and autism.  Such acts of misconduct erode public confidence in the legitimate conclusions of science, putting members of the public in a circumstance where they do not know who or what to believe.  They are inconsistent with the openness that is the very bedrock of science, which seeks to communicate not only what we do know but also what we don’t.  Because if people are to make decisions in their lives based on the results that science achieves, they deserve to know both.

The Labor of Bees

In October last year, an elderly man in Dougherty County, Georgia was operating a bulldozer when he accidentally disturbed a bee colony.  He died after being stung more than 100 times, and investigations into his death confirmed that africanized honey bees have now taken up residence in the state of Georgia.  At least two other hives of africanized bees have since been discovered within the state. 

The first that many heard of africanized bees was seeing The Swarm sometime in the 70’s, an overly sensationalist movie in a decade that saw far too many melodramatic disaster films.  But the underlying premise of the movie — that africanized bees are more aggressive than the strains of honeybees introduced into North America by Europeans in 1691— was essentially accurate.  It was in 1957 that 26 Tanzanian queen bees were accidentally released into Brazil by a beekeeper who was attempting to breed a strain of bees that would have greater honey production than local bees, while also being better adapted to a tropical climate than European bees.  The africanized honey bees that have steadily been expanding their territory into the southern United States are directly descended from those Tanzanian queens. 

The concern to humans and animals over the encroachment of africanized honey bees is surely overblown; since their initial colonization in Texas in 1990, they have been responsible for fewer than 20 human deaths.  The greater concern is with their displacement of the European bee population because of a fundamental difference in their behavior traits.  Africanized bees put greater effort into colony reproduction than do European bees, who instead spend more time on the collection and storage of food, resulting in their critical role of pollenizing roughly 35% of the food supply. 

It seems, though, that the africanized bee is not even the greatest concern facing the European bee population.  In 2006, large-scale losses of managed honeybee colonies were noted in the United States and in parts of Europe.  The impact is perhaps felt nowhere more sadly than West Virginia where, in 2002, the honeybee was named the state’s official state insect.

While similar bee declines have been documented since as early as 1869, the recent reduction was considerably more severe, leading to its characterization as “colony collapse disorder.”  While some speculative ideas have been put forward as possible explanations, including the effects of mobile-telephone radiation (one begins to wonder what cell-phone radiation is not blamed for these days), genetically modified crops, or the effects of global climate change, there is little if any evidence for these mechanisms having an impact on bee colonies.  The reality is likely much more prosaic, with insect diseases and pesticides being the two causes that have received the most study.  Indeed, in October, a paper was published suggesting that the disorder was due to a combination of a virus and fungus that were found in every killed colony that was studied, leading some to claim that the mystery had been “solved.”  Time will tell, but a copy of the paper can be found here.  

What is interesting about the disorder from a legal perspective are the Pollinator Protection Act and the Pollinator Habitat Protection Act, both of which were introduced in Congress in 2007 to provide mechanisms through the Farm Bill to fund a number of programs to research and develop potential solutions.  These programs include the surveillance of pests and pathogens that affect honeybees as well as research into the biology of honeybees so that causes of the disorder can be better understood. 

Last month, the second annual report — also mandated by the bills — was released and can be found here.  It is fair to say that the reported results so far remain inconclusive.  The best hypothesis appears to be that the disorder is a result of multiple factors that may at times act in combination, making the problem a difficult one to solve. 

There is no question about the importance of honeybees to pollination, but the lack of a clear understanding of the population decline has begun to increase interest in promoting alternative pollinators.  While the European honeybee is undoubtedly the most important, it is estimated that there are about 4000 species of bee native to the United States.  Changes in farming practices to promote the activities of these other bee species might help to accommodate the decline.  But one is left with the obvious question:  If the mechanism that is affecting honeybees remains poorly understood, what is the chance that it will eventually spread to other bee species?