Vol. 15, Winter, 1998

Issues in Newborn Screening

Alternative Uses of Guthrie Spots from Newborn Screening Programs Increased Demand for DNA Specimens

Introduction
Attractiveness of Newborn Screening Specimen Repositories
Ethical and Legal Issues Surrounding Alternative Uses of Guthrie Spots
Summary

Introduction
The rapid pace of genetic research which has accompanied the undertaking of the Human Genome Project has led to an unending stream of new insights concerning genetic contributions to human disease, as well as impressive methodological advances in genetic analysis.
For example, buoyed by early success in the identification of the gene for cystic fibrosis, researchers have more recently focused their attention on searching for genetic factors involved in more complex disorders afflicting modern society. Examples include cancer, alcoholism, obesity, diabetes, cardiovascular disease, and psychiatric disorders. The driving force for such studies is more than the academic quest for knowledge. Rather, answers are being sought for the individual and public health problems most affecting morbidity, mortality, and health care costs in our society, and for which traditional approaches seem to have yielded limited success.
Studies of complex disorders require large numbers of DNA samples for analysis. As a consequence, many of the advances made to date in genetic research, particularly those relating to public health issues, have relied upon the use of tissue specimens originally obtained for other purposes. In many cases, the individuals providing the specimens may have had no knowledge that the specimen would be used for any purpose other than testing relevant to their immediate medical care.
As researchers seek to delineate the genetic contribution to multifactorial chronic conditions, such as the question of the degree of penetrance of an allele of the breast cancer susceptibility gene in the population, they require large numbers of DNA specimens from a broad spectrum of the general population.
This increased demand for tissue samples has led to searches for suitable sources of DNA in nontraditional areas, including the specimen repositories of newborn metabolic screening programs. Such demand is reflected in the increased request by public and private agencies for access to samples and in some of the larger states, more than 100 requests were received in 1994.
Attractiveness of Newborn Screening Specimen Repositories
Several aspects of the newborn metabolic screening programs make the blood spots (named Guthrie spots after their inventor) attractive for use in genetic research, population-based epidemiological studies, and other DNA-based testing activities, such as forensic investigation.
First, newborn screening programs are found in all of the states and territories of the U.S. Within these programs, tissue samples (blood) are collected from essentially all live born infants, providing what is potentially the largest and most complete genetic bank and library available in the country.
Secondly, when stored properly, these specimens are stable for a long period of time. Recently, a 20 year-old newborn screening specimen was used as a critical link in the identification of a body in a forensic investigation.
Presently, however, the retention of Guthrie spots by newborn screening programs varies greatly among programs. According to the 1991 CORN (Council of Regional Genetics Networks) report, of the 53 newborn screening programs in the U.S., 27 store their specimens less than one year following completion of analysis, 15 store them from 1-15 years, 6 store them 20-30 years, and 5 store them indefinitely.
Ethical and Legal Issues Surrounding Alternative Uses of Guthrie Spots
Technological developments in the field of genetic testing have outpaced societal development of ethical and legal guidelines for testing. While several states have passed laws attempting to protect the privacy of genetic information, no Federal laws yet exist, despite a recent congressional attempt to pass a Genetic Privacy Act.
Without such protections for genetic research and information derived from it, the enthusiasm over the potential benefits to be gained from access to this vast genetic bank are counterbalanced by the following concerns: the ownership of tissue samples and the genetic information contained therein; requirements for informed consent for genetic testing; and the right to privacy of both the individuals providing the specimens as well as sub-populations of society potentially affected by genetic information revealed.
The issues surrounding ownership of genetic specimens and informed consent for genetic testing are not entirely independent of each other. As previously mentioned, many tissue samples used in genetic studies are originally collected for other purposes, in which case informed consent for the genetic testing would not have been obtained. This is the case with Guthrie blood spots used in state-run newborn screening programs, which are collected for specific testing purposes (thyroid function, PKU, galactosemia, cystic fibrosis, hemoglobinopathies, etc.).
Collection and testing in these programs is mandatory and performed under authority of state law or health department regulation. As such, there is no informed consent in the strictest sense and any additional analyses conducted beyond those mandated by state law or regulation should not be conducted without obtaining informed consent from the provider of the specimen, which is quite impractical in most instances.
This issue gained national attention, and subsequent debates ultimately led to a nation-wide moratorium on the eight-year CDC-sponsored maternal serum prevalence study. In this study, Guthrie spots from newborn screening programs were stripped of identifiers and universally tested for HIV. Some states have attempted to address the limitations of informed consent by including in the description of uses allowed for newborn screening specimens the phrase "other research purposes". Whether this vague clause will withstand legal challenges for all analytical applications is questionable and remains to be seen.
In the end, questions of ownership and informed consent come back to the concern over the privacy of genetic information and the ability of the individual to limit what genetic information is available to third parties. Fears of discrimination, based upon revelations from genetic testing, which could lead to denial or limitation of health and/or life insurance, educational and employment opportunities are not without foundation.
There are unique privacy issues as well, since genetic analyses performed on a tissue specimen could reveal not only information about the individual providing the specimen, but may also reveal genetic information of siblings, parents, and offspring of the individual. Even if privacy laws can be written to protect the individual being tested from adverse repercussions, can they be written to protect relatives of the individual who are unaware that the testing is done, or who may not even yet be born? Should a parent or guardian be allowed to provide informed consent on behalf of a newborn for testing which is not of medical necessity, given the potential ramifications of the testing?
One final concern is that most of the discussion concerning the protection of genetic privacy has focused only on the individual. Similarly, all of the established and proposed legislation aimed at protection of genetic privacy has dealt with the topic by stipulating that all personal identifiers be removed from specimens, such as name, street address, and social security number. Such protections will not adequately protect all individuals, as other non-personal demographic data required for the information to have any value in epidemiological research could be used to identify the individual providing the specimen.
For example, in rural states with low population density and/or high racial/ethnic variation, providing as little information as ethnicity and county of collection will often allow the identification of the individual providing the specimen. Conversely, genetic profile and county of specimen origin could, in some cases, be used to determine race or ethnicity and, subsequently, the personal identification of the specimen source.
The long-standing Federal laws governing informed consent in human research were not only established to protect the rights of the research subject (the individual), but also of the researcher (protection from litigation), and society as a whole. Genetic privacy laws must take into account the need to protect all members of society as well, in order to preclude ethnic, racial, or gender genetic discrimination.
Summary
The rapid and extensive developments in genetic research have created an unprecedented demand for genetic specimens representing a broad spectrum of society. Such specimens are available in the repositories of newborn screening programs.
In the foreseeable future, those individuals entrusted with the protection of these specimens, and delegated the responsibility of responding to requests for access to these specimens, can anticipate a growing demand for access to them for use in genetic research.
As clear legal and ethical guidelines by which these requests can be evaluated do not currently exist, decisions will have to be based upon careful weighing of the potential benefit to be derived versus the potential harm to individuals and society which may result. Such decisions would best be made in consultation with individuals representing a broad range of backgrounds and perspectives. Toward this end, government agencies involved in newborn metabolic screening programs might be well advised to establish formal review panels for the purpose of evaluating requests to access specimens for research.

Contributed by David Mills, Ph.D. (NM)

The Genetic Drift Newsletter is not copyrighted. Readers are free to duplicate all or parts of its contents. The Genetic Drift Newsletter is published semiannually by the Mountain States Genetics Network for associates & those interested in Human Genetics. In accordance with accepted publication standards, we request acknowledgement in print of any article reproduced in another publication. The views expressed in the newsletter do not necessarily reflect local, state, or federal policy. For additional information, contact Carol Clericuzio, M.D., Editor, Department of Pediatrics, The University of New Mexico, Albuquerque, NM, 87131

Table of Contents:
Issues in Newborn Screening:

Introduction
Alternative Uses of Guthrie Spots
Impact of Early Hospital Discharge
Screening for Cystic Fibrosis
Hemoglobinopathy Carriers
Pitfalls in Newborn Screening