This target article considers the relation of fluid cognitive functioning to general intelligence. A neurobiological model differentiating working memory/executive function cognitive processes of the prefrontal cortex from aspects of psychometrically defined general intelligence is presented. Work examining the rise in mean intelligence-test performance between normative cohorts, the neuropsychology and neuroscience of cognitive function in typically and atypically developing human populations, and stress, brain development, and corticolimbic connectivity in human and nonhuman animal models is reviewed and found to provide evidence of (...) mechanisms through which early experience affects the development of an aspect of cognition closely related to, but distinct from, general intelligence. Particular emphasis is placed on the role of emotion in fluid cognition and on research indicating fluid cognitive deficits associated with early hippocampal pathology and with dysregulation of the hypothalamic-pituitary-adrenal axis stress-response system. Findings are seen to be consistent with the idea of an independent fluid cognitive construct and to assist with the interpretation of findings from the study of early compensatory education for children facing psychosocial adversity and from behavior genetic research on intelligence. It is concluded that ongoing development of neurobiologically grounded measures of fluid cognitive skills appropriate for young children will play a key role in understanding early mental development and the adaptive success to which it is related, particularly for young children facing social and economic disadvantage. Specifically, in the evaluation of the efficacy of compensatory education efforts such as Head Start and the readiness for school of children from diverse backgrounds, it is important to distinguish fluid cognition from psychometrically defined general intelligence. (Published Online April 5 2006) Key Words: cognition; cognition-emotion reciprocity; developmental disorders; emotion; fluid cognition; Flynn effect; general intelligence; limbic system; neuroscience; phenylketonuria; prefrontal cortex; psychometrics; schizophrenia. (shrink)

For over four decades, knowledge that symptoms of some inherited diseases can be prevented or reduced via early detection and treatment in newborns has underpinned state-funded screening programs in most developed countries. Conditions for which newborn screening is now a recognized preventative public health initiative include phenylketonuria, congenital hypothyroidism, and, more recently, cystic fibrosis and sickle cell disorder. The use of tandem mass spectrometry to detect conditions such as amino-acidopathies and fatty-acid oxidation defects is also becoming increasingly prevalent. a.

Genetic determinism labels the morally problematical claim that some socially significant traits, traits we care about, such as sexual orientation, gender roles, violence, alcoholism, mental illness, intelligence, are largely the results of the operation of genes and not much alterable by environment, learning or other human intervention. Genetic determinism does not require that genes literally fix these socially significant traits, but rather that they constrain them within narrow channels beyond human intervention. In this essay we analyze genetic determinism in light (...) of what is now known about the inborn error of metabolism phenylketonuria , which has for so long been the poster child ‘simple’ argument in favor of some form of genetic determinism. We demonstrate that this case proves the exact opposite of what it has been proposed to support and provides a strong refutation of genetic determinism in all its guises. (shrink)

The feature article in this edition outlines and then critically examines the Nuffield Council of Bioethics’ Report, ‘Genome Editing and Human Reproduction: Social and Ethical issues’. While Christopher Gyngell, Hilary Bowman-Smart & Julian Savulescu, ‘support the approach taken by the Nuffield Council’,1 their findings are stronger than those in the Report, arguing that - beyond being permissible - many instances of heritable genome editing will be moral imperatives. A collection of engaging responses to this feature article are provided by Rachel (...) Horton & Anneke M Luccason, Pete Mills, and Sarah Chan. As a short-sighed introvert, I am going to leave aside my concerns about Gyngell’s and colleagues’ account of the weak and unhappy gene pool in which I swim, and instead focus on their talk of moral imperatives. Gyngell and colleagues construct their moral imperative argument by way of analogy. The most straightforward, and perhaps most compelling, claim concerns single gene disorders. I reconstruct the claim in the following way: 1. There is a moral imperative to screen newborns for phenylketonuria. 2. If it were possible, there would be a moral imperative to provide replacement enzyme therapy for PKU. 3. By analogy, if it were possible, there would be a moral imperative to make safe genome edits which prevent PKU. The same analogical interference is claimed in arguments in favour of: editing around 27 mutations associated with coronary heart disease, editing to shift individuals of low or …. (shrink)

Newborn screening consists of taking a few drops of blood from a baby's heel in the first week of life and testing it for a list of disorders. In the United States and most countries in Europe, newborn screening programs began in the 1960s and 1970s with screening for phenylketonuria (PKU), a rare metabolic disease that causes severe and irreversible mental retardation unless treated before problems arise. As knowledge about rare diseases expanded and new screening technologies were introduced—such as (...) the tandem mass spectrometer and high‐performance liquid chromatography—the same blood sample could be used to test for a whole list of disorders. In general, screening programs in most countries have tended to expand, but in different countries they have expanded in different ways. Regulation also varies. In some states, screening is mandatory, whereas in others—Wyoming and Maryland—parents are asked for their informed consent. Germany and France have adopted an explicit informed consent procedure, whereas other European countries have a more informal “opt‐out” procedure that does not require signing an informed consent form. Whether newborn screening requires informed consent is an ongoing issue in bioethics. In this article, we will focus on the tension between informed consent and the problem of compliance in newborn screening. Asking for informed consent—allowing parents to opt out—is often thought to pose a threat to compliance. Building on the work of Onora O'Neill on informed consent and trust, however, as well as on work she coauthored with Neil Manson, we will argue that informed consent procedures may actually help maintain trust in newborn screening and may therefore support compliance. (shrink)

Attempts to explain behavior genetically face two major problems: the application of the concept of genetic coding and the theoretical possibility of decomposing behavior. This paper argues that using the notion of genetic coding is appropriate in explanations of protein synthesis but inadequate and even misleading in the context of explanations of behavior. Genes should be regarded as disparate components of mechanisms that account for behavior rather than as codes for behavioral phenotypes. Such mechanistic explanations, however, presuppose the possibility of (...) decomposing behavioral phenotypes, which is strongly disputed by researchers holding an interactionist view of behavior. It is argued that these researchers fail to distinguish etiological from constitutive decomposition, and that their objections apply to the former but not to the latter kind. Constitutive decomposition might identify genes as disparate components and open up the possibility of explaining behavior mechanistically by isolating causal paths from genes to behavior. Finally, research on the single gene disorder phenylketonuria is introduced to illustrate and test these views. With respect to this disorder it is demonstrated that applying the concept of genetic coding would be inappropriate and misguiding, while nonetheless the phenotype is decomposable and can be explained mechanistically by singling out a genetic causal path.t is demonstrated that applying the concept of genetic coding would be inappropriate and misguiding, while nonetheless the phenotype is decomposable and can be explained mechanistically by singling out a genetic causal path. (shrink)

Newborn screening (NBS) began in the 1960s by testing all newborns for a single condition—phenylketonuria, or PKU—which, when identified and treated early, significantly reduces morbidity. Over the...

Irish Supreme Court upholds paramountcy of parental right to determine a child's best interests at the expense of the rights of children themselvesCan a court force on parents who are careful and conscientious a view of their child's welfare which is rational, but quite contrary to the parents sincerely held but non-rational beliefs? The Supreme Court of Ireland has recently held that it cannot do so, and that the Irish Constitution requires that the right of the family to determine its (...) own direction must be respected except in the most narrow of circumstances, such as an immediate threat to the life of the child or risk of serious injury. The ruling leaves the assessment of a child's best interests to the wide discretion of parents, but at the same time fails to offer a means to resolve potential conflicts between the rights of the family and the rights of the child.FACTS OF THE CASEIn North Western Health Board v W 1 an action was brought by a local health board against the parents of 14 month old Paul, seeking a declaration that their refusal to submit their son to the heel prick test for phenylketonuria was a failure to vindicate their son's rights and that it would be lawful to proceed without parental consent. Phenylketonuria is a metabolic condition which can lead to severe and untreatable mental impairment if not detected in its early stages, but a simple variation in diet can stave off this outcome. While Paul's parents did not doubt the veracity of this medical opinion, nor indeed the importance of the test, they refused to subject their son to the invasive heel prick, offering instead samples of urine or hair, such that the test could be carried out by non-invasive means. These means, however, are considerably …. (shrink)

The prevention of disability has been the driving force behind much research. In epidemiology three levels of prevention are defined: primary, secondary, and tertiary prevention. Primary prevention is the prevention of the initiation or occurrence of a disease; secondary prevention is the prevention or amelioration of the consequences of a disease, and tertiary prevention refers to rehabilitation or the limitation of disability associated with the disease. We have examples of all three levels of prevention in the area of childhood disability. (...) Primary prevention is the protection of infants against congenital rubella syndrome by ensuring that women of childbearing age have adequate immunity before they become pregnant. The prevention of choreoathetosis, mental retardation, and deafness, by treating hyperbilirubinemia and preventing kernicterus in newborns, is a great success story in prevention. Similarly, at the level of secondary prevention, is the reduction in mental retardation caused by phenylketonuria, or PKU, by eliminating phenylalanine in the diets of newborns who lack the enzyme to metabolize this amino acid. Tertiary prevention is the area of rehabilitation medicine, and is regarded as the least desirable level of prevention. Indeed, tertiary prevention can be seen as “doing the best we can” in terms of rehabilitation, often while seeking a means of really preventing the disease. (shrink)

BackgroundThis paper represents a portion of the findings from one of the first research studies eliciting the lived experience of adults with an early diagnosis of Phenylketonuria living in Ireland. Ireland has one of the highest prevalence rates of PKU in Europe, however, little is known about the experience of Irish adults with PKU. Furthermore, Ireland is one of the first countries in the world to introduce neonatal screening followed by the introduction of long-term dietary therapy over 50 years (...) ago. This study presents the first comprehensive assessment of the lived experience of Irish adults with PKU on long term dietary therapy.MethodsNarrative data was collected from eleven self-selected participants, using semi-structured interviews. The interviews were divided into five sections focused on eliciting a holistic understanding of the lived experience of adults with PKU living in Ireland. Thematic analysis was guided by Colaizzi's Framework in conjunction with NVivo qualitative data analysis software.FindingsFindings from the original research encompassed a broad understanding of the lived experience of adults with PKU living in Ireland, including factors influencing dietary therapy and managing PHE blood levels. The themes being discussed within this article are those which appear to be least represented within current literature: living with PKU, including reproductive health, the importance of self-management and establishing routine, support networks in adulthood and concerns regarding aging with PKU.ConclusionIt was evident from the findings that a diagnosis of PKU can influence how adults with PKU may experience aging and their own mortality. These findings offer new insight into the vulnerability attached to the experience of aging with PKU and may be beneficial to advocacy groups and for future development of policy and practice. (shrink)

It is now widely accepted that the concepts of “health” and “disease” in psychiatric and psychological contexts are value laden. In this article I argue that even in the realm of physical illness and disease (appendicitis, phenylketonuria, etc.), the concepts of “health”, “illness” and "disease” are value laden. I explore the four most common bases used to objectively ground the key concept “normal functioning”, namely, genetic structure, evolutionary fitness, non-premature death and absence of pain. I argue that they all (...) fail to adequately provide an objective grounding for the. concept “normal functioning” (health) and, hence, for “abnormal functioning” (illness, disease). The reason an objective grounding cannot be given is that physical “health”, “illness” and “disease” rest on widely shared values in addition to the condition of the organism. (shrink)

Virtually every infant in the United States (U.S.) undergoes a heel stick within the first week of life to test for a variety of metabolic, endocrine, and hematological conditions as part of state-run universal newborn screening (NBS) programs. In the U.S., NBS began in the 1960s for phenylketonuria (PKU), a metabolic condition that causes intellectual disability if left untreated. I review the history of how NBS came to be a mandatory public health program that did not require parental consent1 (...) and examine whether the policy was morally justifiable. I then examine how three changes to NBS programs are prompting a re-evaluation of the mandatory nature of NBS. The three changes are: (1) the implementation of .. (shrink)

Newborn screening for the genetic disease phenylketonuria (PKU) is generally considered the greatest success story of applied human genetics. Even those generally skeptical of the value of genetic testing often comment enthusiastically on this program. In fact, PKU screening has been plagued with serious problems since its inception in the early 1960s. This essay describes some of these difficulties and asks what lessons they hold for other screening programs. It also argues that realism in our assessment of such programs (...) requires that we pay greater attention to the concrete experience of families. How screening should work in theory is of less importance than how it does work in practice. (shrink)

Should research on the possible genetic components of human intelligence be carried out? I first try to provide some general guidelines as to whether any particular piece of research should be undertaken and then consider the specific example of the ethics of genetic research on intelligence. The history of the debate on intelligence does not make one very optimistic that the fruits of such research would be used wisely. However, there are indications that people’s understanding of the nature of inheritance (...) may be improving and it could be that such research might have significant benefits. It is worth remembering than the condition phenylketonuria, a genetic disease in any useful sense of the term, and one that leads to mental retardation (i.e. very low intelligence), is now wholly preventable, and indeed very largely prevented, through environmental intervention. (shrink)

Given the scarcity of educational materials (EM) to guide nutrition education strategies for phenilketonuric (PKU) patients, the goal of the present study was to develop and analyse the appearance and content validity of a EM directed to phenylketonuric children and their caregivers. The EM was evaluated by five professionals with expertise in the management of PKU. The material comprised 20 pages. All categories presented a satisfactory Index of Content Adequacy, meaning that the material was coherent, relevant and well structured. The (...) final Flesch Reading Ease Score index was 77. The ‘ABC of Phenyl’ Manual is appropriate and therefore suitable for use as an adjuvant in the management of phenylketonuria with pediatric patients. (shrink)

As the 20th century began, few effective therapies existed. This soon changed with major therapeutic discoveries turning the century into what has been called the golden age of therapeutics.1 The emphasis of most of these developments was on medicines for common disorders as they presented the greatest need. However, it also allowed pharmaceutical manufacturers to produce blockbuster drugs that provided a large return on investment. Rare disorders were overlooked because most are genetic in origin and scientific knowledge was lacking, making (...) it difficult to find treatments. The first genetic disorder with a therapy was phenylketonuria. The biochemist who proposed the first successful treatment in the 1950s was actively discouraged as phenylketonuria was genetic and ‘incurable’.2 Another reason was an absence of incentives to invest in developing medicines for which the return was limited, given the small numbers of potential patients. This changed from 1983 as several countries began introducing orphan drug policies, with Canada being a notable exception. As the millennium changed, some drugs for rare disorders were available, but the sequencing of the human genome in the early 2000s provided scientific knowledge to develop many more. The new therapies are often costly because they require millions, even billions, of dollars and years to develop, test and satisfy regulatory standards. …. (shrink)

The genetic testing and screening of children has been fraught with controversy since Robert Guthrie developed the bacterial inhibition assay to test for phenylketonuria and advocated for rapid uptake of universal newborn screening in the early 1960s. Today with fast and affordable mass screening of the whole genome on the horizon, the debate about when and in what scenarios children should undergo genetic testing and screening has gained renewed attention. United States professional guidelines — both the American College of (...) Medical Genetics /American Society of Human Genetics statement and the American Academy of Pediatrics Statement on the genetic testing of children and the new AAP and ACMG joint policy statement and technical report — as well as the old UK guidelines by the Working Part of the Clinical Genetics Society and the new United Kingdom guidelines by the British Society of Human Genetics all give the same answer: genetic testing and screening should only be done if it is in the child’s best interest. (shrink)

Behavioral genetics has as its goal the discovery of genes that play a significant causal role in complex phenotypes that are socially relevant such a parenting, aggression, psychiatric disorders, intelligence, and even race. In this article, I present the stories of the discoveries of three such important phenotypes: maternal nurturing behavior and the c-fosB gene; intelligence and phenylketonuria ; and pair-bonding and monogamy and show that the reality is considerably more complex than often portrayed. These accounts also lay bare (...) some fundamental misconceptions of this field in which genes hold a privileged place and inherently subjective phenomena are mistakenly objectified. (shrink)

Parents, providers, policy makers, and the public need to talk about the implications of advances in genomic technologies for state run newborn metabolic screening programs. Technologies, such as highly multiplex testing and whole genome sequencing, are raising old issues with new urgency and are posing new challenges that threaten to overwhelm newborn screening programs.Newborn screening programs in their current form were born in the late 1960s. Robert Guthrie developed a screening test for phenylketonuria that could be performed on blood (...) spots collected on filter cards that Guthrie also developed. States rapidly established newborn screening programs, which were almost always mandatory, in response to advocacy by geneticists and parents. Although the programs initially varied in form and experienced significant pushback from the medical community, by the early 1970s, all states had established programs with centralized laboratories, and the medical community had come on board. (shrink)

Parents, providers, policy makers, and the public need to talk about the implications of advances in genomic technologies for state run newborn metabolic screening programs. Technologies, such as highly multiplex testing and whole genome sequencing, are raising old issues with new urgency and are posing new challenges that threaten to overwhelm newborn screening programs.Newborn screening programs in their current form were born in the late 1960s. Robert Guthrie developed a screening test for phenylketonuria that could be performed on blood (...) spots collected on filter cards that Guthrie also developed. States rapidly established newborn screening programs, which were almost always mandatory, in response to advocacy by geneticists and parents. Although the programs initially varied in form and experienced significant pushback from the medical community, by the early 1970s, all states had established programs with centralized laboratories, and the medical community had come on board. (shrink)

Genetics offers real opportunities for public health actors. Increased understanding of genetics will illuminate some of the factors that affect disease and, in many cases, will lead to more effective treatments. The recognition that phenylketonuria was caused by a metabolic defect that led to the accumulation of toxic levels of phenylalanine, an elevation that could largely be averted by adopting a low-phenylalanine diet, is an early example. Some cases of what was thought to be Sudden Infant Death Syndrome, a (...) diagnosis used when no etiology is known, now appear to have been caused by metabolic defects in fatty acid oxidation and sodium channel defects. One of the tasks that has already been undertaken by the public health sector is to ensure that genomic information is incorporated into clinical care when the robusmess of findings and their clinical utility have been well defined. (shrink)

Genetics offers real opportunities for public health actors. Increased understanding of genetics will illuminate some of the factors that affect disease and, in many cases, will lead to more effective treatments. The recognition that phenylketonuria was caused by a metabolic defect that led to the accumulation of toxic levels of phenylalanine, an elevation that could largely be averted by adopting a low-phenylalanine diet, is an early example. Some cases of what was thought to be Sudden Infant Death Syndrome, a (...) diagnosis used when no etiology is known, now appear to have been caused by metabolic defects in fatty acid oxidation and sodium channel defects. One of the tasks that has already been undertaken by the public health sector is to ensure that genomic information is incorporated into clinical care when the robusmess of findings and their clinical utility have been well defined. (shrink)