The Most Noble Ends

“I’ve noticed that everybody that is for abortion has already been born.”

                                                                                           Ronald Reagan, 1980


It is no secret that Ronald Reagan took positions that were strongly opposed to abortion, at least at the time of his Presidency.  After he won the 1980 election, the first thing he said at his first press conference was that he would “make abortion illegal,” and he maintained a strong anti-abortion stance during his years as President.  He consistently opposed not only efforts to maintain the legality of abortion procedures in the United States, but also implemented peripheral policies that sought to advance the objectives of the so-called “pro-life” movement:  school authorities were required to notify parents if their children sought contraceptives at school clinics and workers at family-planning clinics who received federal funds were forbidden to present abortion as a medical option to pregnant women.  And, of course, he was opposed to stem-cell research. 

It is thus a particular irony that since her husband’s death, the most poignant of Nancy Reagan’s few comments on policy have been to advocate support for stem-cell research.  It was in 2004, just months after Ronald Reagan’s death, that she publicly responded to President Bush’s decision to limit funding for such research, criticizing his decision and expressing her opinion that too much time had already been wasted discussing the issue.  In 2009, she publicly praised President Obama for his reversal of the Bush policy. 

But Obama’s decision to lift restrictions on federal funding for embryonic stem-cell research has not been without consequences.  I commented several months ago about the case of Sherley v. Sebelius here in which District Court Judge Royce Lamberth held that the Dickey-Wicker Amendment prohibited federal support of such research, a decision that would have had even more impact on the federal funding of stem-cell research than even the Bush restrictions.  In light of the report in Nature last week that induced pluripotent stem cells — which, unlike embryonic stem cells, can be created without the destruction of embryos — might be rejected by a patient’s own immune system, it seems valuable to review what has happened with Sherley since last August.  A copy of the Nature paper can be found here (subscription required). 

The Dickey-Wicker Amendment is one that no Congress or Administration —Democrat or Republican —can credibly criticize since it has been passed by all as part of the Labor, Health and Human Services, and Education appropriations acts every year since 1995.  It has been passed not only with the signature of Republican President Bush, but also with the signatures of Democrat Presidents Clinton and Obama, after being enacted by both Democrat- and Republican-controlled legislatures.  After the District Court found that funding of embryonic stem-cell research violated the Act and refused to issue a stay until the appellate court reviewed the decision, the Court of Appeals for the District of Columbia itself stayed the action pending its review.  On April 29, the appellate court issued its ruling, vacating the preliminary injunction and allowing federal funding of embryonic stem-cell research to continue. 

In my earlier post, I commented that as “much as I personally support investigations into the use of embryonic stem cells because of their tremendous potential in the treatment of disease, I have difficulty faulting the Court’s decision.”  I found the language of the Dickey-Wicker Amendment unambiguous and dismissed attempts to parse it differently as “contrived.”  Two of the three judges on the Court of Appeals disagreed. 

The Dickey-Wicker Amendment states that “[n]one of the funds made available in this Act may be used for … (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero ….”  The reasoning of the two-judge majority is one that had been rejected in the lower court, namely to parse what the statute means by “research.”  Essentially, investigations into embryonic stem cells require two phases:  a first phase in which embryos are destroyed and the stem cells are derived; and a second phase in which experiments are performed on the already derived stem cells.  The argument accepted by the appellate court is that federal funding of the first phase is prohibited but not federal funding of the second phase since only the first phase constitutes “research in which a human embryo [is] destroyed.” 

To reach this conclusion, the majority notes the use of the present tense in the statute (“are destroyed” instead of “were destroyed”) and consults some online dictionaries for definitions of the word “research.”  I am always wary of these kinds of analysis, which can give the impression of constructing a post-facto rationale for a decision improperly made for other reasons.  Such analysis is too much like relying on the exploitation of loopholes and technicalities instead of principled application of the law as it was written.  I therefore find myself sympathetic with the dissent’s criticism that the judges in the majority have performed “linguistic jujitsu” and “taken a straightforward case of statutory construction and produced a result that would make Rube Goldberg tip his hat.”  A copy of the full opinion and dissent can be read here

Researchers are generally pleased with the ruling, but in many ways that represents a short-sighted view.  The problem with the Dickey-Wicker Amendment is especially apparent when the procedural posture of Sherley as it now stands is considered.  So far, the only issue that has been resolved is whether experiments involving embryonic stem cells are “research in which a human embryo is destroyed.”  The case now returns to the District Court for consideration whether such experiments are “research in which a human embryo … is knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero,” a question that potentially raises a host of different arguments.  While it is possible to take other procedural actions at this point — request a rehearing en banc by the full Court of Appeals or petition the Supreme Court to hear the case — those other actions almost certainly represent too much risk to stem-cell researchers. 

As difficult as it may be to do politically, it strikes me as much easier to find a way to avoid the annual ritual of having the Dickey-Wicker Amendment added as a rider to funding bills.

What is the Army Doing with your Baby’s Blood?

Like many, I used to love watching The X-Files. The appeal of the show was not just the intricacy of the plot, which had seemingly endless layers of conspiracy, but was also because of the clever way in which factual information was interleaved with fiction, almost making me “want to believe.” One of the most memorable scenes occurs in the show’s third season in an episode titled “Paper Clip,” an obvious reference to the post- World War II “Operation Paper Clip” program by the Office of Strategic Services to sanitize the histories of Nazi scientists so that they could obtain security clearances in the United States. Mulder and Scully find themselves in an abandoned mine in West Virginia. The cavern is filled with filing cabinets, housing “lots and lots of files,” as Scully so artfully described it. Inside the cabinets are smallpox vaccination records and tissue samples collected as part of the Smallpox Eradication Program, creating a comprehensive genetic database for every man, woman, and child born since the 1950’s.

It was creepy. And it made me think about the scar I have on my left shoulder from my own smallpox vaccination.

It is hard not to be reminded of that X-Files episode when reading the complaint in the case of Jeffrey Higgins v. Texas Department of State Health Services. Filed at the end of 2010, the case relates not to smallpox vaccination but to newborn blood screening. In an effort to aid parents in the identification of genetic disease of their newborn child, every state in the United States operates a newborn screening program, and many other countries have similar programs. Such programs began in the late 1960’s and have been expanded over the decades so that virtually all of the 4,000,000 infants born in the United States each year have their heel pricked to collect a few drops of blood around the second or third day of life. Exceptions are rare.

The screening is valuable and provides parents with important medical information that may allow infants born with genetic conditions to have those conditions addressed right from the beginning of their lives. But it is not much of a stretch to understand why medical researchers might have a broader interest in the collection of these samples. Rather than being concerned with a single infant’s condition, the availability of a comprehensive database of newborn blood samples would allow a wide variety of studies to be conducted, looking at patterns of disease that could have profound implications for addressing public-health objectives.

Indeed, in a report published this week in the journal Pediatrics, a copy of which can be found here (subscription required), the authors note the increasing research interest in newborn blood samples. A contract awarded by the National Institutes of Health in 2009 was specifically to develop a “repository of dried bloodspots that is either virtual or physical and comprised of those stored by state newborn screening programs and other resources.” There are certainly positive objectives that could only be reached with access to such blood databases. But the problem is that, in the same way that I found Mulder and Scully’s discovery creepy, many people are uncomfortable having their children’s blood stored in a government database.

This discomfort is justified. There are currently few laws that limit the type of research that may be conducted and most states have no requirement to notify parents that the blood samples may be retained and used for other purposes than the screening of their newborn children. It’s probably fair to say that most never even considered what happened to the blood after collection.

The Higgins case has its origins in an earlier case filed in 2009 when five families sued the Texas Department of State Health Services for the unauthorized storage and use of newborn blood spots. A settlement was negotiated in which Texas agreed to destroy some 5,000,000 newborn blood samples that had been collected and retained since 2002. The Texas legislature also acted — not to limit retention of samples but to provide express government authorization for future samples to be retained. Higgins was filed when it was later revealed that about 8800 samples had been turned over to an Armed Forces laboratory as part of an effort to build a national mitochondrial DNA registry. The stated purpose of the database is forensic, namely to provide a tool by which missing persons may be identified and to aid in the resolution of other difficult cases.

The complaint in Higgins, a copy of which can be found here, alleges that Texas has acted deceptively: “Defendants have knowingly, deceptively, routinely, unlawfully and without the knowledge or consent of the infants’ parents, sold, traded, bartered, and distributed blood samples … to private research companies, government agencies, and other third parties.” A report published by The Texas Tribune that can be found here seems to confirm that records now released by the state “show an effort to limit the public’s knowledge of aspects of the newborn blood program, and to manage the debate around it.” The Tribune skeptically describes “oversights” in response to its requests for information, a pattern of suppressing disclosure about activities related to the blood program, and efforts to “plant” information with sympathetic lawmakers.

I have no doubt that blood databases such as are envisaged have the potential for enormous public good by allowing researchers access to a body of information that is nowhere else available. But the privacy concerns are obvious. Of course people weigh these countervailing issues differently, but the only way to settle the tension between them is by discussing them openly and candidly. One benefit of cases like the one in Texas (and a similar one that failed in Minnesota in 2009) is that public visibility over blood programs is increasing so that that discussion can take place.

Rule, Supremacy, and Sway

When the Oklahoma State Trooper came upon the scene on November 13, 1974, it seemed apparent enough that the 28-year-old woman had died in a sleeping-driver accident.  There were no other automobiles involved and the pattern of evidence was classic. 

But the facts surrounding the death of Karen Silkwood were suspicious.  Her blood contained 0.35 mg / mL of methaqualone (Quaalude), roughly double the level needed to induce drowsiness.  While it might have been possible to dismiss the accident as resulting from a young woman in the 1970’s ingesting too much of a common-enough recreational drug, there were too many other contextual factors over the preceding week for such a conclusion to be readily accepted. 

When she died, Silkwood had been returning from a meeting of the Oil, Chemical, and Atomic Workers’ Union, and was on her way to meet a journalist.  It is believed that she had been gathering evidence on behalf of her union to support a claim that her employer — the Kerr-McGee plutonium fuels production plant — was engaging in negligent safety practices.  She was by then known as somewhat of a troublemaker.  Already earlier that summer, she had testified about improper safety practices at the company to the Atomic Energy Commission. 

On three distinct occasions during the week before her accident, Silkwood found herself contaminated by plutonium.  The incidents required not only that she undergo decontamination procedures but that her apartment and roommate also be subjected to them.  Many of her belongings needed to be destroyed during the course of the decontamination procedures.  The source of the plutonium contamination remains unclear.  Many believe that Silkwood was a victim of retaliation for her whistle-blowing efforts, while others claimed that she had deliberately contaminated herself as part of an orchestrated effort to generate negative publicity for the company. 

After her death, Silkwood’s father brought an action against the plutonium plant, during which a jury that considered the detailed facts rejected the theory that she had deliberately contaminated herself.  Indeed, the jury awarded $505,000 in compensatory damages and $10 million in punitive damages under Oklahoma state law.  But that decision was not to be the end of the case.  There was an important conflict between federal and state law that ultimately needed to be resolved by the Supreme Court of the United States. 

Under the federal system of the United States, the Supremacy Clause of the U.S. Constitution requires that “the laws of the United States … shall be the supreme law of the land … anything in the constitutions or laws of any State to the contrary notwithstanding.”  Such preemption means that when there is a conflict between federal and state law, the federal law prevails.  And in the Silkwood case, there was a relevant provision in the Atomic Energy Act, which had been passed by Congress in 1954.  In that act, Congress granted the Nuclear Regulatory Commission (then the Atomic Energy Commission) exclusive authority to set safety standards in the nuclear industry.  Barring some minor lapses, Kerr-McGee had generally complied with those federal regulations. 

When the Court of Appeals for the Tenth Circuit heard the case, it reduced the total award to a mere $5000 (the amount of the property damage when Silkwood’s belongings were destroyed), finding that Oklahoma state tort law had been preempted by the federal Atomic Energy Act. 

The case illustrates the dramatic consequences that can result from the act of federal preemption in specific areas — a difference in result between $5000 and one well in excess of $10 million.  Last week, the Supreme Court of the United States considered another case that turned very much on the issue of federal preemption, but this time in the context of the so-called “Vaccine Court.”  A few months ago, I commented on the case here, just before oral arguments were to be heard. 

Created in 1986 by passage of the National Childhood Vaccine Injury Act, the Vaccine Court has a very limited and specific role:  it applies a form of “no fault” system to the adjudication of injuries that result from the administration of vaccines.  The court was created in response to vaccine-related tort actions, most particularly in response to use of the diphtheria, tetanus, and pertussis (“DTP”) vaccine, which was being blamed for an increased incidence of certain developmental disorders in children.  There was a real concern that the potential tort liability for vaccines was driving vaccine manufacturers from the market, and that this was at odds with the government’s public-health objectives. 

The creation of the Vaccine Court and a no-fault system of adjudication gave vaccine manufacturers a concession by limiting their liability in a highly predictable way.  While the structure of the system was successful in stabilizing the vaccination market, the clear downside is that the no-fault nature of the program may provide insufficient safety incentives to vaccine manufacturers and that some of those who are injured by vaccines are significantly limited in their legal recovery, often limited to recovering awards that are significantly less than their actual damages.  Those who suffer the greatest harms would very much like to have access to state tort laws as an avenue for recovering their full damages and it is difficult not to be sympathetic to those innocent children who had reactions to vaccines that significantly impair the quality of their lives. 

There is an important similarity between regulations of safety practices in the nuclear industry and the administration of the Vaccine Court — in both cases, Congress’s decision to preempt a portion of state tort law potentially has the effect of barring people who suffer from very real injuries from recovering their full damages.  In passing this kind of legislation, Congress presumably believes that a broader purpose is served by excluding legal options that would otherwise exist.  The task of the Supreme Court when confronted with such cases is, though, to decide the precise scope of what Congress has preempted and whether it is constitutionally permitted to do so. 

The Supreme Court did ultimately consider the Silkwood case, and reversed the appellate court to reinstate the large damages award.  A copy of the court’s decision in Silkwood can be read here.  But in the case decided last week, the Court upheld the framework of the Vaccine Court, holding that all design-defect claims against vaccine manufacturers are preempted.  A copy of that decision can be read here.  Why the difference? 

The answer is simple— the decisions hinged critically on the statutory language chosen by Congress, with the Court determining that it was Congress’s intention to exclude all avenues of recovery for faulty designs of vaccines except through the Vaccine Court.  The question remains, though:  Given what we know about the safety issues that exist with vaccines, the effect on public health of having them administered, and the impact on manufacturer behavior resulting from its insulation from state tort liability, is Congress’s choice a wise one or a foolish one?

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.