Knowing Sin

One of the most famous quotations attributed to J. Robert Oppenheimer was made in a lecture he delivered at MIT in 1947, a little more than two years after the destruction caused by detonation of two atomic bombs in Japan to bring a decisive end to the second World War.  The more than 100,000 deaths that resulted from one of the best organized scientific projects in history still epitomize the potential that scientific activities have in providing tools for devastation.  Oppenheimer said:

Despite the vision and farseeing wisdom of our wartime heads of state, the physicists have felt the peculiarly intimate responsibility for suggesting, for supporting, and in the end, in large measure, for achieving the realization of atomic weapons.  Nor can we forget that these weapons as they were in fact used dramatized so mercilessly the inhumanity and evil of modern war.  In some sort of crude sense which no vulgarity, no humor, no overstatement can quite extinguish, the physicists have known sin; and this is a knowledge which they cannot lose.

J. Robert Oppenheimer

I was reminded of Oppenheimer earlier this month when the U.S. National Science Advisory Board for Biosecurity (“NSABB”) made the decision to interfere with publication of scientific research in the name of security.  The NSABB is an advisory committee whose origins are found in the Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology, convened by the National Academies in 2002 when the widespread fear precipitated by the anthrax attacks of 2001 was still fresh in people’s minds.  The so-called “Fink Report,” eponymously named after the chair of the Committee, included a number of recommendations intended to “ensure responsible oversight for biotechnology research with potential bioterrorism applications,” one of which was the creation of the NSABB.  A copy of the report can be found here.  The primary focus of the NSABB is oversight of “dual-use research,” i.e. biotechnology research that may have both legitimate scientific purposes and that may be misused to cause threats to public health.  In many ways, the comparison with nuclear research is apt because of the potential for nuclear research to find beneficial applications in power generation and medical imaging as well as its infamous destructive applications.

The action taken this month by the NSABB represents its first intrusion into the independent publication practices of scientific journals.  The issue is research on H5N1 bird-flu mutations by Dutch scientists that would allow considerably easier human transmission of the virus — which has mortality rates in the neighborhood of 60%.  While there is a fear of potential terrorist uses, there is no question that the research also has important public-health and viral-research implications.  In its press release, the Board noted that it had asked editors of Science and Nature, as well as the authors involved, to suppress what is, by any measure, information long viewed as essential to the need in scientific research to reproduce the results of others:  “[T]he NSABB recommended that the general conclusions highlighting the novel outcome be published, but that the transcripts not include the methodological and other details that could enable replication of the experiments by those who would seek to do harm.”  A copy of the full press statement issued by the Board can be found here.

The whole notion of limiting access of details only to those who would not “seek to do harm” is, of course, problematic.  One need only recall the anthrax attacks of 2001, which in many ways provided the original impetus for formation of the NSABB itself.  During investigations of those attacks, the two individuals most prominently identified as the subjects of interest by federal prosecutors were U.S. biodefense researchers who had access to classified information.  Restriction on publication of information by journals like Science and Nature would have had no effect in preventing those attacks, but would still remove valid scientific information from the public archive.

Many viral scientists have objected to the move by the NSABB, characterizing it as a form of censorship, which it indeed is.  I admit to considerable sympathy with the views of those critics, and again turn to Oppenheimer, whose words capture the sentiment that most scientists share:

There must be no barriers to freedom of inquiry….  There is no place for dogma in science.  The scientist is free, and must be free to ask any question, to doubt any assertion, to seek for any evidence, to correct any errors.  Our political life is also predicated on openness.  We know that the only way to avoid error is to detect it and that the only way to detect it is to be free to inquire.  And we know that as long as men are free to ask what they must, free to say what they think, free to think what they will, freedom can never be lost, and science never regress.

Is this a hopelessly naïve and unrealistic view?  While I desperately wish it were not, and while I normally argue as passionately as I am able that science is better for its openness, I also have sober moments when I pause uncertainly.  I encourage those who wish to understand both sides of this particular issue to read the blog post by virologist Vincent Racaniello here, particularly the comment added by NSABB member Mike Imperiale.

As an attorney, I frequently find myself defending reports of jury decisions that strike much of the public as outlandish.  My usual response is that it is astonishingly presumptuous to suppose that spending five minutes reading a short news report of a verdict can in any way compare to the weeks of deliberation and examination of documents that caused twelve people to come to some agreement about the issue.  As I face my own initial distaste for suppression of legitimate scientific information, I think of the time that the members of NSABB presumably spent grappling with these issues and I am haunted by my own argument — they are far more knowledgeable about biology than I am and surely as sensitive to the need for science to operate in an atmosphere of openness.

Still, I expect that no matter how genuine their efforts to prevent it, it is merely matter of time until biologists know sin in the way physicists of the 1940’s did.

Crime and Punishment

In the year 2000, a Virginia woman received some of the worst news possible when her young daughter approached her to discuss some  things that had been making her uncomfortable.  The daughter recounted recent episodes of her 40-year-old stepfather (the woman’s husband) making subtle sexual advances towards her over the last several weeks.  Subsequent investigation by the wife uncovered her husband’s expanding cache of magazines devoted to child pornography, the collection of which had been accompanied by increasingly frequent visits to Internet pornography sites and the solicitation of prostitutes at local massage parlors.

It is easy to understand her reaction, particularly since her husband worked as a schoolteacher:  The result was his legal removal from their home, a conviction for child molestation, treatment with the chemical-castration drug medroxyprogesterone, and a requirement that he attend a rehabilitative twelve-step program for sexual addiction.  The program was unsuccessful — he persistently solicited sexual favors from both the staff and clients at the rehabilitation center.  He was accordingly sentenced to a prison term.

The case was a fascinating one because the specific cause of his pedophilia was identified by neuroscientists who treated him when he presented himself at the University of Virginia Hospital on the eve of beginning his prison sentence, complaining of a headache.  MRI scans identified an approximately egg-sized brain tumor located in the right lobe of his orbitofrontal cortex, an area of the brain known to be correlated with social integration, judgment, and the acquisition of a moral sense.  Damage to that area had previously been identified in certain sociopaths.  Removal of the tumor resulted in a reestablishment of his previous sense of morality, and he returned to his home.  When he began to complain of headaches in October 2001 and had resumed his secret collection of child pornography, a further MRI scan revealed regrowth of the tumor.  His pedophiliac behavior again disappeared after removal of the second tumor.

This case serves as a striking example for the emerging field of “neurolaw,” and I have chosen it for two reasons:  first, it presents one of the most clear illustrations of a link between a specific neurology and criminal behavior; second, it involves a crime that is so offensive that many — perhaps most — would agree that it should be punished even as we agree that it was not the man’s “fault” that he developed a brain tumor.  The example is one that figures in the report released by The Royal Society in the UK this month entitled “Neuroscience and the Law.”  A copy of the report can be found here and the original report by neuroscientists about the patient described above can be found here.  Other aspects of the interaction of neuroscience and law are also of interest, and I may discuss them in future posts, but today I want to limit the focus.  What should the role of criminal punishment be as neuroscience allows us greater insight into the mechanism by which some individuals commit crimes?

Legal philosophy generally identifies four justifications for criminal punishment, although there is sometimes blurring in how they are  categorized by different thinkers:  incapacitation (the criminal must be rendered unable to continue committing the offense); deterrence (punishment must be visible so that others who might be inclined to commit the offense will be deterred from doing so); retribution (the criminal must suffer in some proportion to the suffering he caused in his victims); and rehabilitation (the punishment should operate so that the criminal will understand and accept the wrongness of his actions in a way that will change his future behavior).  Different people place a different level of importance on each of these justifications depending on their own personal philosophies, but virtually everyone recognizes the legitimacy of at least some of them.

In thinking about pedophilia — even pedophilia induced by a brain tumor — it is impossible not to continue to accept incapacitation as a justification for punishment.  Removing the ability to commit the crime is important in protecting children, particularly in circumstances where the person is driven by impulses so strong that he is unable to control them.  Similarly, deterrence has a legitimate role to play in influencing those who may experience similar but controllable impulses by demonstrating the consequences if they give in to them.  And from a retributive perspective, there is no difference in the harm caused to a victim simply because the biological reasons for the  commission of the crime are better understood.

Where a greater understanding of the origins of a crime play the most significant role is in the rehabilitative role of punishment.  That greater understanding allows responses to be fashioned that take account of the underlying neurological causes of crimes so they can be corrected.

But lines can still be difficult to draw.  We all know — people have always known — that there are those born with a predisposition to commit certain kinds of crimes.  To understand where that predisposition comes from because of a better understanding of neurology in no way changes the fact that our societies do believe that punishment is an appropriate response even when that predisposition results from factors outside an individual’s control — genetics, birth defects, formative social environments and pressures, etc.

Pedophilia arouses strong reactions in people.  But the same philosophical principles that continue to demand that we punish it apply to every crime, including those that may not be viewed as passionately.  Even as we come to understand the human brain more fully and to develop an appreciation of how its structure may be linked to crime, the philosophical bases upon which we have traditionally justified punishment remain essentially unchanged.  Those philosophies have been debated for centuries and while there are always issues at the fringes, they are almost universally accepted.

Still, it is unsettling to accept the reality that neuroscience is exposing:  one day you might be punished as a child molester when your real crime is to have developed cancer.

Gene Patents

Not a day goes by that breast cancer does not figure in the news, at least at some level.  There are reports of new treatment options, reports of high-profile women who have been diagnosed, reports of improvements in early detection, and many other stories of how it affects our lives.  With approximately 12% of women likely to develop an invasive form of the disease sometime during their lives, there are few among us who are not impacted by it.

In 1994 and 1995, the BRCA1 and BRCA2 genes were isolated (the name of the genes is derived from “BReast CAncer”), representing one of the most significant advances in understanding the disease.  Women who carry mutations of these genes have an 82% risk of developing breast cancer and a 54% risk of developing ovarian cancer by age 80.

This ability to test for mutations has radically altered the lives of many women.  Before isolation of the genes, women who had a family history of breast cancer lived much of their lives under the assumption that it was merely a matter of time before they developed it also, and often feared that their daughters would one day endure the same heartbreak they had seen in their mothers.  Genetic tests for mutations now offer many greater options for women.  Those who test negative for the mutations are provided with reassurance not only that they are not at increased risk for breast cancer but that their children are also not carriers.  Those who test positive have a more realistic assessment of their actual risk and can avail themselves of options that range from increased monitoring to prophylactic mastectomy.

While no one disagrees that the ability to test for the genes is a positive development for women, many people object — strongly object — to the fact that there is a government-enforced monopoly on the right to administer such tests that was granted to the company Myriad Genetics.  Information about the test, called BRACAnalysis® is available at the web site here.  The cost of the test is somewhere around $400 for a single-mutation analysis (useful if the woman has a known family history involving a specific mutation) and somewhere greater than $3000 for a full-sequence analysis of both BRCA genes.  There is no question that these costs are elevated from where they would be in a competitive market because of the monopoly held by Myriad Genetics; if other companies were permitted to offer similar tests using the technology, competition mechanisms would drive costs lower.

The monopoly held by Myriad Genetics is, of course, a consequence of the patent laws.  Myriad Genetics owns a number of patents directed to isolated forms of the genes themselves and to methods for analyzing a patient’s BRCA sequence.  The patents grant them the right to prevent others from performing the BRCA tests, and they actively make use of that right.  Earlier this week, an appeal was filed with the U.S. Supreme Court challenging the validity of Myriad Genetics’ patents.  At the heart of the issue is the fundamental question:  should companies be allowed to patent genes?

Many believe that corporate profits in an area such as this are unseemly, and it is impossible not to have at least some sympathy with their point of view.  Currently, access to an important genetic test is denied to those women who do not have either the independent financial means or health insurance to pay for it.  A broad public policy that allows gene patents will inevitably result in other genetic tests having similar financial barriers.  Further, it has always been the case that laws of nature and physical phenomena cannot be patented.  Those opposed to gene patents essentially argue that human genes should not be patented because they are created by nature, not by men.

These are important and valid points that need to be considered by the Supreme Court if it chooses to accept the case.  But they fail to tell the whole story and are misleading when presented without a fuller context.

When the Myriad Genetics case was litigated in the original court, the argument that genes were products of nature prevailed, resulting in a ruling that the patents were invalid.  But this was overturned by the appellate court, which noted an important distinction between genes as they occur in the human body and genes that have been isolated:  “BRCA1 and BRCA2 in their isolated state are not the same molecules as DNA as it exists in the body; human intervention in cleaving or synthesizing a portion of a native chromosomal DNA imparts on that isolated DNA a distinctive chemical identity from that possessed by native DNA.”  A full copy of the appellate decision can be read here.  It is that distinction between genes as they occur in the human body  (only as a component of very long strings of chemically linked nucleotides) and genes after they have been isolated (where they consist of only about 0.1% of the nucleotides of the original DNA molecule) that is at the heart of why gene patents are currently valid.

Beyond this technical reason, though, it is worth recognizing the policy issues that argue in favor of allowing gene patents.  Foremost is the fact that the patent monopoly is temporary — the earliest of the Myriad Genetics patents on this technology will expire in about three years, after which the ability of competitors to provide similar services will progressively open up and drive down costs.  In evaluating the prudence of allowing gene patents, it is a mistake to look only at the circumstances during the period when the patents are enforceable — everyone agrees that monopolies have negative consequences on trade, but it is the price we temporarily agree to pay in order to have the technology commercialized in the first place.

Medical scientists also know that BRCA1 and BRCA2 are only a small piece of the puzzle that defines the genetics of breast cancer.  There are many other discoveries yet to be made, and the cost of the research to make those discoveries is large.  The possibility of obtaining a patent that allows a profit to be realized is a major incentive that promotes private investment in the research.

Consider the following choice.  Is it worse to endure a temporary period of time in which our access to technology is limited, leaving the right to profit from it exclusively with those who developed it?  Or is it worse to endure not having the technology at all?  The answer really is no different for genetics than it is for other technologies.