Ethical Issues Surrounding Newborn Medical and Genetic Screening: Project Update

It has been some time since I have written here concerning the UROP project with Professor Tabery. Since I am presenting today at the capital, I thought I'd share this with everyone as well.

Currently, there are over 1,200 tests available to determine the genetic component of various medical disorders, predispositions, and traits. The state of Utah currently mandates that 46 screening tests be performed on all newborns to identify and treat certain disorders. The number of genetic tests will increase in the future, requiring policymakers to make decisions concerning what tests to require, allow, or prohibit. Guidelines for making such decisions require standardized, objective criteria; however, critical analysis of the criteria to justify these decisions is lacking in scientific and public policy literature.

In 1968, Wilson and Jungner were the first to develop criteria for making such decisions. In 2004, the American College of Medical Genetics developed more sophisticated criteria for newborn screening tests. Our analysis found that these criteria either consist of ambiguous language or are insufficient when applied to some current newborn screening tests and some tests for disorders currently being debated for possible mandate. Our research also found that significant variation exists between states related to newborn screening ranging from 17 to 53 mandated tests. Our goal is to provide policymakers with usable guidelines to make informed, ethical decisions for requiring, allowing, or prohibiting newborn screening tests. Our guidelines include two philosophical concepts necessary to make an informed, ethical decision concerning permissibility:

1. Understanding of the causal relationship between genes and disorders. The genetic component must be high in order for the state to consider a newborn screening test mandatory. In addition, the causal relationship between genes and disorders must be morally positive or neutral and free from scientific controversy. All tests within the impermissible category have a significant environmental component or are morally controversial related to causation and/or treatment.
2. Treatability. In order for a test to be mandatory, the treatment must be readily available, of reasonable cost to the parents, and benefit the least advantaged. A test may still be mandated by the state if it does not meet these criteria if and only if it is of significant public health concern and is currently under debate for possible public assistance related to treatment. We name the first category as mandatory-treatable (MT) and the latter as mandatory-informational (MI).
   

The following provides a brief outline of key concepts and arguments that we have developed to support this legislative formula.

The causal relationship between genes and phenotypic traits or disorders is important in the permissibility debate on newborn screening because it relates to a level of confidence medical professionals and patients may place in test results. In the traditional equation for phenotypic expression, P = G + E + (G x E), G must be high and E negligible for any test to be considered mandatory. This means that scientific consensus must conclude that a test have an insignificant environmental (E) component in order to justify mandatory testing and have a high correlation between specific genetic markers and expression of disorder near or at 100%. If there is a high genetic component but expression is not at or near 100%, then it may still be considered MI or permissible. In regards to justifying permissible or impermissible newborn tests, we argue that that the causal understanding of the genetic component may be high or low but are excluded from the mandatory category due treatability factors discussed below. The paradigmatic disorders for both ends of this spectrum include phenylketonuria (PKU) on the mandatory side and anti-social personality disorder (ASPD) on the impermissible side.

Newborn testing of PKU utilizes high-performance liquid chromatography (HPLC) as part of a tandem mass spectrometry (TMS) panel in most states. This tests for the genetic markers associated with the absence of an enzyme necessary to break down phenylalanine. Without this enzyme, the brain builds up toxic levels of phenylalanine resulting in mental retardation, brain damage, and eventually death. Early detection and a carefully controlled diet free of phenylalanine prevent morbidity and mortality in those individuals with this genetic disorder. The genetic component in this case is 100% with no environmental component in the expression of the disorder. The expression correlation of this disorder is also 100%. If a child is born with the defective gene, he or she will develop the disorder. PKU was the first newborn screening test used in the United States and is part of the mandatory testing program in each of the 50 states.

ASPD is a psychiatric condition symptomatic of behaviors associated with the term "evil" or "predator". The terms "sociopath" and "psychopath" are also sometimes used to describe a person with ASPD. Characteristics of the disorder include deception, violence, criminal acts, lack of empathy, and disregard for social norms. Many with ASPD simply do not seem able to emotionally differentiate or "morally" restrain their actions. Poverty, alcoholism, and drug abuse also are related to ASPD. It is estimated that in the U.S. general population as many as 5.8% of males and 1.2% of females meet the criteria for ASPD while the incidence in U.S. prison populations is anywhere from 50-80%. A genetic test for ASPD has been proposed that determines the markers associated with low levels of monoamine oxidase A (MAOA), correlated with ASPD in conjunction with severe childhood maltreatment. The association of ASPD with low levels of MAOA functions off an interactive predisposition model developed and is significantly impacted by the environmental component in expression of the disorder. No states currently require newborn testing of MAOA although its requirement was proposed by former British Prime Minister Tony Blair before the House of Commons in 2005. We argue that screening for this disorder should be impermissible because the high environmental component associated with its expression and the controversy surrounding genes and behavior. The causal component must be understood in consensus with the scientific community to have a genetic component of near 100% and be free from association related to behavior or other moral considerations that are still currently under debate. We believe that testing for ASPD in newborns represents a clear case of a test that should be made impermissible by the state.

Treatability is also important in any decision factoring for mandatory, permissible, or impermissible newborn testing. The American College of Medical Genetics (ACMG) developed criteria in 2004 that includes scores for availability, cost of treatment, efficacy, and benefits to both the individual and society. We argue that although this is a significant improvement from the ambiguous language used in the Wilson and Jungner criteria, it is still missing an important component related to inequality and social justice. This component derives from philosopher John Rawls’ Difference Principle from his work A Theory of Justice. The Difference Principle states that any system of justice must address the need and indeed benefit the least advantaged within the system. He also argues that even though the system will allow for inequality, it should be minimized at birth so everyone starts with an equal opportunity. This is important to any legislative decision regarding newborn screening because the state should not perpetuate or increase differences between classes of people. In other words, any test that is possible for mandate in the future must be treatable by means of availability, benefit, and cost across all classes of people including the least advantaged. Any newborn test for which treatment perpetuates or increases inequality between classes should be judged impermissible by legislators. Any test that is deemed permissible may involve treatment that is morally neutral or does not promote any type of inequality.

The role of the legislature as it relates to newborn screening must address the needs of public health and rights of the individual. Our formula includes the components of causal understanding of the underlying genetic mechanisms and a universal notion of treatability that follows a theory of justice. This will give legislators the tools to evaluate both current newborn screening tests for possible revision and more importantly, future tests that may not be as paradigmatic as PKU or ASPD. Our formula will also help standardize the number and type of newborn screening tests performed between states so that all American newborns may have a healthy start on life. We believe the newborn screening issue and our proposed solution is both conceptually important and practically necessary in the field of medical ethics.

Conscience As It Relates To Natural Religion: An Analysis of John Henry Newman

In Fifteen Sermons Preached Before the University of Oxford Between A.D. 1826 and 1843 (15S) and An Essay in Aid of a Grammar of Assent (GA), John Henry Newman compares natural religion to that of revealed religion in an apologia of faith. I will provide an overview of his definition of natural religion including how it changes over the course of his writings. I will then argue that the faculty of conscience is the common thread that holds his definition of natural religion together between the two works. Lastly, I will explore whether conscience is sufficient to keep Newman’s definition of natural religion coherent within his argument for revealed religion.

In “Sermon II: The Influence of Natural and Revealed Religion Respectively” (15S), Newman attempts to show how Christianity as authenticated, revealed religion relates to natural religion. He starts by claiming that, “No people (to speak in general terms) has been denied revelation from God …” He says that only a portion of the world; however, enjoy authenticated revelation, which refers to the Christian God of the Gospels. He then introduces a definition of natural religion as an attainable creed that arises from this general revelation evidenced by the writings of pious men from what he calls the heathen world. This is still too general a definition for his purposes but he must get past some of the prima facie objections that the term “Natural Religion” carried with it in the eighteenth century. It is here that he introduces conscience as an obvious and essential principle of religion. Conscience allows an understanding of the difference in the nature of action and motivates one to act in one way over another. Happiness begins to be associated with acting in favor of conscience because we vaguely feel remorse when we act against it. The idea of evil is also associated with the feeling of acting against conscience and together with general revelation, a presentiment of life after death and judgment of our deeds begins to form. Happiness is then connected with right action, which then becomes the basis of an individual moral system. From here, a disciplined mind might develop a religious creed that points to the individual’s idea of moral truth. Keep in mind that the source of the religious creed arose out of conscience but even though it may be built from there on the principles of logic and observations of nature, it remains problematic.

Newman claims that this is how natural, religious creed is attained; however, is not truly attained because others reach different conclusions pointing in a different direction of moral “truth”. The mind may go in the direction of philosophy, which would make the religious creed too abstract, or it may go in the direction of rude natural feeling, which would make the religious creed unintelligible. What seems to be lacking in natural religion is an insight into God’s true personality and a doctrine for moral action that points in the direction genuine moral truth. Authenticated or revealed religion provides this deficiency. Natural religion allows for deep and true religious feeling but with an object to place affections and a standard by which all can gauge moral action. Revealed religion provides the unity of a “Judge and Governor” to keep any corruption of reasoning in check. A large portion of his work is how reason functions in relation to faith, which is beyond the scope of this essay, but it is important to note that natural religion relies more on obedience to moral principles by reasoning alone while teaching religious truth by investigation. Revealed religion enforces obedience more on faith and teaches religious truth historically. Revealed religion engages the faculty of faith, indeed all of our faculties more completely, and as such, it fulfills our nature in a way that natural religion is never able achieve. From Fifteen Sermons, the crucial point to remember is that natural religion prepares the mind for the moral truth and recommends doctrine that revealed religion brings.

It is interesting that the definition of natural religion depends, in a large part, on the definition of revealed religion. This works well in supporting his argument that there is a relationship between the two but I will now discuss how Newman’s definition for natural religion changed over the next 20-40 years as evidenced in A Grammar of Assent. In “Chapter Five: Apprehension and Assent in the Matter of Religion” (GA), Newman considers the dogmas of belief in one God, the Holy Trinity, and dogmatic theology in addition to their relation to notional and real assent. He claims that it is natural to associate empirical evidence of nature with an individual outside of our senses. He then claims that God indirectly gives us through our conscience an insight to His nature. This is the first departure from how he postulated conscience as a starting point for natural religion in Fifteen Sermons. Now he argues that revelation works through conscience rather than as a separate phenomenon. Further, he refers to a child’s response to conscience and states, “The child keenly understands that there is a difference between right and wrong; and when he has done what he believes to be wrong, he is conscious that he is offending the One to whom he is amenable, whom he does not see, who sees him. His mind reaches forward with a strong presentiment to the thought of a Moral Governor, sovereign over him, mindful, and just.” This is another departure from his argument in Fifteen Sermons because he is now claiming that conscience more directly leads to the truth of revealed religion versus a process that requires introduction to the doctrine and truth of the Holy Bible. Lastly, he implies in §1 “Belief in One God” of the same chapter that natural religion relates to notional assent. In his introductory comments, he distinguishes between real and notional assent by associating religious acts with real assent and theological acts with notional. This entails that natural religion is a theological or an intellectual endeavor and therefore more abstract. Here again, he generalizes natural religion into one category of the abstract versus into two categories of abstract or rude natural feeling that arise from the development of a religious creed as posited in Fifteen Sermons.

The differences between the definition of natural religion in Fifteen Sermons and Grammar of Assent may be subtle but I argue that it is significant enough to require a defense of its coherency. My claim is that there may be contextual differences that are explanatory to the differences. Fifteen Sermons fits within the context of a sermon while Grammar of Assent is a philosophical treatise defending Catholic faith. It is beyond the scope of this essay to more fully detail why there are differences in his definition but I argue instead that the faculty of conscience lends support to the coherency of his conceptualization. Since I developed the role of conscience in Fifteen Sermons, I will now focus on Newman’s concept of conscience in Grammar of Assent to support my claim.

In §1 of Chapter 5 (GA), Newman first addresses conscience as mentioned above. He then expands on his definition of conscience along the same lines from Fifteen Sermons in addition to claiming its legitimacy alongside memory, reasoning, and imagination. Further, he discusses the consequences of conscience, which are a moral sense and a sense of duty. This is in line with how he previously conceptualizes the essence of natural religion in Fifteen Sermons. Remember that conscience allows a moral system to develop or be a consequent from the vague apprehension of right and wrong. He asks us to consider conscience as, “ … not as a rule of conduct, but as a sanction of right conduct. This is its primary and most authoritative aspect.” He expands here on his original definition again by discerning conscience from taste and claiming that conscience concerns itself primarily with people and the actions of people or with the self and actions of the self. According to Newman, taste relates more to aesthetic preferences for beauty and ugliness rather than the rightness or wrongness of action. The important point is that his definition so far remains coherent concerning the faculty of conscience between the two works. Lastly, he adds to the definition of conscience by stating, “… when the conscience is good, as real though less forcible, self-approval, inward peace, lightness of heart … constitute a specific difference between conscience and other intellectual senses … indeed they would also constitute between conscience and moral sense…” The disconnect between the concept of natural religion in Fifteen Sermons contrasted with Grammar of Assent becomes less incoherent when attention is focused on the faculty of conscience. The idea of what natural religion is and how conscience relates to it must arguably be teased apart more in Grammar of Assent; however, the same structure of natural religion is apparent when evaluated as a consequent of conscience. The disconnect then may be attributed to contextual differences and sheer length of time between the two works. His conceptualization of conscience evolved over the course of years but the primary function, definition, and relationship to natural religion remains the same.

The question remains whether conscience is a sufficient explanation to maintain coherency and therefore validity of his argument distinguishing natural from revealed religion. Although I argue that conscience supports a claim of coherency between the two definitions, it is not sufficient to completely define natural religion because of his appeal to revealed religion. This is the inherent weakness of his argument in that he defines, in a large part, what natural religion by what is not. For Newman to provide a stronger argument for a relationship between natural and revealed religion he would have to better define natural religion on its own. Secondly, he minimizes religions that have similar agency and doctrine as the Judeo/Christian system. He does refer to Islamic faith as false against the argument that it is also a revealed religion in “Chapter 10: Inference and Assent in the Matter of Religion” (GA); however, it not sufficient to say that one religion is natural while another is revealed simply because the tenets are different. His argument for revealed religion as a logical consequent of natural religion, which is a logical consequent of conscience, rests upon structure. He must therefore focus on the differences in structure between different religious creeds to distinguish Judeo/Christian faith from all others. I argue that the phenomenon of conscience supports a theistic worldview in that it seems to point in the direction of moral truth without proof. This implies, as Newman would agree, that there is something intangible and objective outside of ourselves. It is only a small leap from here to entail theism. I also argue in conclusion that more work to Newman’s argument must be made before Christianity can truly claim itself to be authenticated, revealed religion. Conscience as the starting point may yet provide an argument to better support his claim.