Geneticists have been quick to realize that collections of tissue samples may be immensely valuable in research on gene structure and in research on gene frequencies in the populations. Particularly tempting are the collections of blood spots that are gathered from the newborn population as part of state-funded programs to detect and treat phenylketonuria, sickle cell anemia, congenital hypothyroidism, and a few other early onset diseases. About 4 million newborns are screened in public programs each year; so newborn screening creates an immense set of samples that could be extremely useful in answering questions in human and medical genetics.
The genetics community enthusiasm has been tempered by skepticism on the part of some about the propriety of using stored samples. What are the legal and ethical implications of using archived samples in genetics research? One major concern is the issue of informed consent in newborn screening, and the fact that there are often few provisions for obtaining a parent's prior permission for the participation of a newborn in a screening program. Alternatively, some geneticists have argued that the consent of parents is unnecessary if the stored samples are used "anonymously" in research projects, but there is no consensus about what actually constitutes anonymous use. Finally, a few researchers have voiced concern about the interests of individuals in genetic information that may be discovered in the future that could have an impact on the lives of the source persons.
(1) What are the principles of informed consent that we should respect in screening programs? (2) What constitutes "anonymous" use of archived tissue samples? (3) Is the geneticist or researcher obligated to convey new genetic information to persons who are the sources of archived tissue samples?
The new dilemmas of informed consent in newborn screening are not difficult problems to overcome. Perhaps the most reasonable solutions to these dilemmas will rest on devising one set of guidelines for the use of collections of samples that are already housed in archives, and a second set of guidelines that will govern informed consent and the use of collections that are assembled now and in the future.
Existing collections of samples may be reasonably used for research purposes under two sets of circumstances. (1) Source persons, or their parents, should be (re)contacted for specific, current consent. Although this approach affords maximum respect for the personal autonomy of source persons, practical logistics may be formidable, even insurmountable. (2) Archived samples may be used for research provided that they are uncoded and are completely anonymous. The first of these 2 approaches would provide maximum flexibility for the source person to learn about new genetic information, while the second approach would preclude any further contact with the source person - a situation that could abrogate at least some of the source person's further right to exercise his or her own autonomy.
Protocols for collecting samples now and in the future should include provisions for obtaining parental consent for newborn screening. This consent protocol should also include information about the possible future use of samples for novel genetic studies. Choices that are presented to parents should be clearly worded and clearly dichotomous. With some attention to these ideas, we should be able to create interactions that are, both respectful of individual rights and personal autonomy, and compatible with the interests of the genetics research community.
More recently, state-funded programs have approached the idea of informed consent in newborn screening from several perspectives that give more or less consideration to parental autonomy and the right of parents to make decisions on behalf of their minor children. But provisions for informed consent vary considerably among jurisdictions. At one extreme are two jurisdictions that require parental consent before any samples are collected from the newborn infant. At the other extreme are two states that have such rigid mandates that parents are not allowed to refuse even on the basis of their religious beliefs, and two states that provide criminal penalties for parents who refuse to allow their infants to be tested. Most states, however, do allow parents to refuse testing, based on their religious beliefs, and most states also provide some mechanism for obtaining parental consent, even if consent is sought only after blood samples have been collected from the infant! What is singularly lacking in provisions for informed consent is explicit permission for future use of samples that are stored away after newborn testing is complete.
Issues of informed consent have already received considerable attention from the Committee on Assessing Genetic Risks, of the National Science Foundation's Institute of Medicine (Andrews, et al., 1994). However, there is continuing lack of uniformity in legislative provisions for informed consent in newborn screening. A model protocol for informing mothers, or parents, about the newborn screening process and the implications of future use of stored samples is needed.
While many investigators acknowledge the current dilemmas of informed consent in newborn screening, the movement to gain access to archived tissue samples continues to gain support in the scientific community. A number of investigators have suggested that all archived samples should be available to researchers who agree to use the samples "anonymously." To this end, the American Society of Human Genetics recently organized a Rapid Action Task Force on Informed Consent for Genetic Research, chaired by Dr. Ed McCabe. The Task Force has distinguished between retrospective studies (using old collections of samples) and prospective studies (using new or future collections of samples), and between anonymous samples and "anonymized" samples. When the Task force consulted with the Social Issues Committee of the Society, the Committee recommended that informed consent should not be necessary in retrospective studies using anonymized samples, nor in prospective studies using anonymous or anonymized samples. One of the difficulties that I see with this approach lies in potential confusion over the definition and implications of the words "anonymous" or "anonymized."
The implications of future anonymous use of surplus samples include the content of informed consent in the newborn screening process. I would suggest that even the possibility of future use of samples, beyond the purposes of newborn screening, should be presented to parents. Parents may agree to coded or to fully anonymous use of their children's samples in future research. However, the investigator should include in the information imparted to parents the possibility that newly discovered information might be of consequence to their children or to themselves. Parents who elect coded use of their children's samples might opt to receive such information at some future time, while parents who opt for fully anonymous use of samples must understand that such use precludes the possibility of conveying new information to themselves or their children.
We acknowledge the concern that,"no one can give a blanket consent for future use of stored samples." My response to this opinion is, "Why not?" If information about genetic studies, and the ramifications of future studies, is presented to parents clearly, then parents should be in a position to make a rational and informed decision about future use of the samples that they or their children have supplied or donated.
The fact that many geneticists and researchers have hesitated about using archived tissue samples indicates at least an intuitive awareness of respect for persons who are the sources of surplus or archived samples. On the one hand, this intuition indicates that source persons, or the parents of infant sources, should have at least some role in deciding about future use of samples. On the other hand, researchers who are oriented toward developing new knowledge, perhaps in the "academic" sense, argue that anonymous use of old samples is not only justified, but is also separate and apart from any obligation to the source person.
Ideally, the professional who desires to use collections of archived samples would contact all source persons to obtain current informed consent with little or no trouble. However, recontacting parents of former newborn populations is a prohibitive task. When we now balance the immense logistical problems of obtaining new consent for using old samples, and the immense knowledge that may be derived from contemporary research efforts, we may realize the most benefit to mankind by permitting anonymous use of existing collections of samples. We might strive for the ideal of recontacting parents while simultaneously developing reasonable requirements for genetics investigators.
So...., mindful of ethics and the concept of good faith, the professional community can well institute new protocols that will provide for obtaining parental consent, in the present, for use of samples in the future. Parents who are now participating in newborn screening programs should be approached with information about the immediate purposes of screening and about possible future use of the samples. Consent for both purposes should be elicited in two steps: parents should not be confronted with a single choice - Yes or No - when the choice entails decisions on several distinct issues. Rather, each opportunity for choice should be presented in clear, concise language, with a clear, dichotomous choice at each step. After a description of the project, there should be an explanation of the options available for the participants, including their right to withdraw without prejudice and their right to change their minds if they haven't already made an irrevocable decision. Finally, parents should be asked direct questions about their willingness to participate in each phase of the project.
