Thursday, January 29, 2009

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.

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