Two roads converge: the challenge of human subject protections in the forensic DNA research context.

Introduction: A Contemporary Challenge to the Rights and Welfare of Human Subjects in Research

History is replete with examples of the propensity of humankind to throw caution to the wind when searching for and learning about the untapped potential of scientific discovery in research. Sometimes this lack of caution has been the cause of tragedy. Two major instances immediately spring to mind: The Holocaust of World War II and the Tuskegee Syphilis Experiments conducted by the United States Public Health Service on poor disadvantaged African-Americans in the period between 1932 and 1972. Both disregarded the well being and rights of the individuals that were involved in the respective experiments. Some conjecture today that we may be on the cusp of a horrific deja vu.

We live in the information age. Knowledge and information are power. Important information such as characteristics, disease, and personality is personal. Much of this information is locked inside of our DNA. Advances in modern science have provided keys that can unlock this mysterious Pandora's Box. Does the unlocking of our personal characteristics from our DNA pose dangers in human research?

Consider the following scenario which may not be that far fetched. Imagine going out for a meal and having a glass of water; then someone comes along, takes the glass, and through a simple manipulation, removes thousands of cells that you left behind. The DNA is extracted from the cells, copied, and then profiled, exposing genetic information that was unknown to you. Is this possible at the present? Yes. Is this happening in today's society? Unknown--for the moment! There would be nothing you or anyone could do about this situation. You did not consent to the testing, nor did you have a say as to who sees your information.

The gleaning of information from DNA samples occurs daily around the world in different settings. Two of those settings involve research and diagnostic applications. Typically these applications are looking for hereditary information (paternity or lineage) and genetic history (predisposition to disease or disorders). Law enforcement/forensic science uses a third application in which DNA information generates a genetic profile to serve as an identification tool. The profile is defined and stored in a database, and a sample is then stored in a DNA repository for future analysis at the discretion of a law enforcement agency. Could this sample be considered anonymous if used in a forensic DNA research study? The use of DNA in forensic science application makes an individual's DNA code a unique identifier. When DNA is used post-factum for research purposes, what ethical challenges are emerging for human subject protections and specifically what rights and privileges must one relinquish or be required to relinquish as a prisoner?

This question provides the essential energy behind the discussion to follow. To approach this question it will be necessary to focus on three areas: 1) The identifiable nature of forensic DNA samples; 2) the inviolability of privacy, confidentiality, and informed consent in human research; and 3) the question of exemption under 45 CFR 46.101.b.

Ultimately, in this discussion what emergent challenges exist for research administrators and the role of leadership we are asked to provide for our respective communities and institutions?

Focus on Science: The Identifiable Nature of Forensic DNA Samples

The first step in the exploration of the present discussion must be an examination of the identifiable nature of DNA samples. DNA profiling is a process that begins when a minute sample of genetic material - DNA - is taken from human tissue. The process ends when the sample is given a computerized numeric value in the form of a bar code and stored in a database. DNA can be collected from individuals using a variety of samples including blood, semen, saliva, hair root, or bone. The technique that is most favorable due to its non-invasive nature is the mouth swab. Once the sample is collected, the DNA must be processed or profiled. (Rudin & Inman, 2001)

Taking a DNA profile involves analyzing it at 13 different locations (also referred to as loci) from various parts of the molecule. Statistically, no two people (except identical twins) are likely to have the same profile. This would seem to make DNA a unique personal identifier.

DNA profiling or analysis is a complicated process and is carried out in sequential steps. The generated profile is stored in the appropriate database. Identification of a particular individual is possible by the profile and the sample because the profile is specific to individuals much like a fingerprint or another unique human identifier. However, the question is what are the implications of DNA profiling and the storage of samples from which they have been harvested?

On the positive side, the world of jurisprudence has benefited greatly from the unique abilities of DNA profiles. Examples of such benefits are the rapid and absolute elimination of innocent suspects, culminating in the speedy identification of offenders with a very high degree of certainty. The reliability of evidence produced in court makes for better administration of justice, which leads to an increased public confidence in the criminal justice system. This potentially has a deterrent effect on offenders, which could lead to a concomitant decrease in crime, thus increasing cost-effectiveness in terms of investigation time saved. But are the results totally positive? Does this technology have any negative and potentially destructive implications? One place to examine this is the world of human subject research.

Focus on Ethics: Privacy, Confidentiality, and Informed Consent as Central to Human Subject Protections

Significant and highly charged, popular discussions suggest that DNA profiling poses great difficulties in the areas of human rights and personal freedoms (American Civil Liberties Union, 2002; Human Research Protection Program, 1996; National DNA Data Bank Advisory Committee, 2002; Rooker, 2000; Rothstein, n.d.; Wines, 2002). Such difficulties would be especially important for scientific research and the demands of ethical leadership for research administrators. To explore these facets, reflecting upon the ethical and regulatory guidance concerning privacy, confidentiality, and informed consent relative to human research is important.

The Nuremberg Code 

The Nuremberg Code established ethical, medical and scientific norms for human research protection in response to the atrocities of the Nazi Holocaust during World War II. The code is comprised often separate points. Summarized, the Code articulated that the voluntary informed consent of the human subject was absolutely essential to protect the rights of the individual. The Code recognized that unnecessary pain and suffering must be avoided and that the benefits of research to individuals must outweigh potential risks. The Code became the foundation for later principles and regulations that have since guided investigators and provide contemporary parameters for the conduct of human subject research. While the Code does not specifically address privacy and confidentiality per se, its concern for the protection of human rights clearly is predicated upon concepts of individual human freedoms from which privacy and confidentiality necessarily arise.

The Belmont Report 

In the United States the central hub of human research protections is The Belmont Report of 1979. The objective of the Report was to provide the philosophical and ethical framework for the protection of human subjects in research regardless of discipline. The Report articulated three ethical foundations and the application of these principles in the conduct of human subject research.

I. Respect for persons

This principle addresses the need to protect the autonomy of individuals and to provide special protections for those who have diminished autonomy.

2. Beneficence 

This principle addresses the need to protect the wellbeing of human subjects through a careful balancing of all risks and benefits such that risks are minimized and benefits are maximized.

3.Justice

This principle requires the equitable selection of research subjects and the equal distribution of risks and benefits.

The Belmont Report brings into sharp focus the practice of these three principles when it addresses the needs for the process and procedures of informed consent. The Report requires that informed consent provide complete information in a way that can be fully comprehended by research subjects while guaranteeing they are free from all forms of coercion. The Belmont Report provides the foundation upon which the concepts of privacy, confidentiality and informed consent are shaped in The Common Rule.

45 CFR 46 (The Common Rule)

45 CFR 46, first adopted in 1974 by the then-Department of Health, Education, and Welfare as its policy for the protection of human subjects in research, represents today the culmination of more than forty years of development and discussion on the ethical principles, guidelines, and regulations for conducting research using human subjects. After 1991 when sixteen other federal departments adopted 45 CFR 46, it became known as The Common Rule. It established the parameters and core procedures needed for the protection of human subjects in research, such as the requirements for informed consent and the authority of Institutional Review Boards (IRB).

Of the fifteen elements of informed consent, eight are required and the other seven are at the discretion of the individual IRB. Among the required elements for informed consent is that an individual's right to privacy and confidentiality must be secured. The purpose of the informed consent document is to provide information to the potential research subject such that the subject can make an informed decision about participating in the research project. The information given to the subject must provide sufficient information about the research, may not be coercive or exert undue influence, and may not contain any exculpatory language such that a subject would waive legal fights. In short, an informed consent document reflects the deeper, more substantive, and more critical process of informed consent that is predicated upon an agenda of trust between research staff and the individual participant.

The language in The Common Rule on the requirements for informed consent indicates there is the chance that an individual investigator may not always have a clear and full understanding of all of the factors or issues involved in evaluating potential risks and ensuring full and complete protections. To assist, an IRB serves as a check and balance in the research process by acting as advocate for the research subject and for society at large. By protecting the rights and welfare of the research subject, an IRB champions society's belief in the tight to protection for human subjects in research, including the right to privacy and confidentiality as prescribed in the critical elements of informed consent as found in The Common Rule.

The Health Insurance Portability and Accountability Act 

The protection of an individual's right to privacy and confidentiality is underscored by the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Though HIPAA does not concern research exclusively, the Act does affect how protected health information should be used in research situations.

As the ethical principles for human research articulate society's commitment to the protection of human subjects, HIPAA is intended similarly to set a high bar for the protection of an individual's right to confidentiality and privacy in the use, storage, and transmission of protected health information. While HIPAA itself has been the source of contest and debate concerning its usefulness or even its necessity, HIPAA's enduring significance may be in its raising up, at least on the level of intentionality, society's need to secure complete respect for the right to privacy and confidentiality of every individual.

Focus on the Dialectic: DNA Samples, De-Identification, and Qualification for Exemption under 45 CFR 46.101.b

A variety of concerns emerge when considering the ethical protection of human subjects and the complex issues surrounding DNA profiling and its impact upon privacy and confidentiality. Since even the most cursory overview of such concerns would be far too exhaustive for the purposes of this discussion, it will focus on consideration of the potential qualification of exemption for DNA samples under 45 CFR 46.101.b.

The overall intention of Paragraph 101 is to detail the scope and applicability of the activities that fall under the requirements for the protection of human research subjects. However paragraph 101.b allows for six categories of activities to be determined as exempt from the regulations. These six categories seem to hold in common a low risk for violations of the right of an individual to privacy and confidentiality. Among the categories for exemption is the use of pathological specimens and diagnostic samples if they are publicly available and cannot be linked back to the individual.

In the light of the discussion of the second section in this paper, the question is can samples collected in current or future forensic DNA research be exempt under 45 CFR 46.101.b? Since the fundamental purpose of a DNA database is to identify, thereby testifying that a DNA sample is a unique identifier, can research that involves the collection or study of DNA specimens from sources that have previously been stored in a database be considered as anonymous either theoretically or practically?

How does this issue of viewing DNA as a unique identifier impinge on the ethical principles and guidelines of The Nuremberg Code, The Belmont Report, and The Common Rule? Are these principles and regulations designed to deal with such an issue? Do they effectively consider the problems and issues that are potentially caused by such a potent and discriminating tool? Granted, a research subject's DNA profile would have to be previously entrenched in a database for the subject's DNA to be identified in a research study. However, is this concept closer than we realize?

Lest it be thought that this DNA database/databank issue would only affect those incarcerated or embroiled in the justice system, one should be aware that newborns today are subjected to DNA screening for a number of hereditary diseases prevalent in the general population. Once the screen is performed and the information is gleaned and stored in a database, the sample itself is stored in a repository. (Rudin & Inman 2001) Extrapolating from this simple and increasingly commonplace medical practice, one might be tempted to project a potential, however remote or seemingly implausible, promiscuous use of such DNA information or samples.

Conclusion: The Ethical Pledge of Human Research Protections And the Mission of the Research Administrator

The potential to catalogue and maintain the genetic code of an entire population is both exciting and daunting. In one respect the incidence of certain diseases could be significantly reduced due to earlier detection. In jurisprudence the administration of justice would be more effective and efficient. In addition, the events and aftermath of 11 September 2001 would seem to make DNA profiling more palatable in the interests of personal, national, and global security against the evil of terrorism. Without question the global outpouring of concern over the events of September 11th makes extremely understandable a desire to use DNA profiling to discover the identity of any potential terrorist. (Waak 2002)

Conversely such a position is not without serious critics. Those who advocate civil liberties in the United States and around the world articulate serious concerns: Do the benefits provided by this tool outweigh its risks? Who will protect the autonomy of the individual in light of the power of this rapidly more common technology? If each person were to have his or her DNA profile stored in a database, who would protect his or her privacy and confidentiality?

By utilizing the power of DNA analysis and profiling, a government could become the Orwellian Big Brother with the power to identify and control the individual in the interests of totalitarianism. (Waak 2002) In the end there would be not benefits and the costs would be far more than the mind can bear. Who are the guardians that can raise the implications of the potential ethical erosion that might be possible? This task is not just for the philosopher or theologian. It is also for the research administrator who oversees and shapes the fundamental act of research when it involves human subjects.

In recent years, a growing number of voices are calling attention to standards for the responsible conduct of research. These standards include much more than human research protections. Concomitantly, the role of the research administrator has evolved far beyond managerial functions and compliance oversight. Research administrators are becoming part of an unforeseen intertwining of the intrinsic need to see ethics and professional integrity as a fundamental part of research and not apart from it as an addendum or a matter of post-award inspection.

Being caught up in this new energy in the mission of research administration and being confronted by complex issues such as those of human subject protections in the light of DNA profiling, research administrators need to take seriously three important tasks. First, regardless of whether it concerns human subject protections or another aspect of the field, research administrators must know the full scope of what is expected not just legally, or for regulatory affairs, but also ethically. This requires the professional to go beyond knowing the cognitive content of regulations to appreciate their meaning, or as philosophers refer to it, their "ontology." What is the meaning of a specific regulation? Why did it occur? Second, research administrators need to learn how to interpret and adapt ethical requirements for specific issues. Regulations are not necessarily univocal. They need to be adapted and shaped to meet the challenges of any set of circumstances in any given time and place. And third, research administrators must be ready to make major revisions and reforms to existing policies and practices to meet new understandings of ethical horizons or to meet unforeseen circumstances.

In the final analysis, research administrators have a critical function to call attention to what is emerging in the research life of an institution and the ethical impact that will follow. In this regard, the two roads of ethics and industry, of research production and research protections, meet and converge and collide in the mission of the research administrator and the fundamental act of research. The research administrator must know how to negotiate the inevitable collision and harness the ensuing energies when road meets road. We wonder which to trod; but we know--we know that, almost paradoxically and impossibly, we must follow both!

The discussion above on human research ethics and the challenge of DNA profiling bring into high relief the critical leadership of research administrators--a leadership that calls our institutions and investigators to follow the highest calling of research itself, namely the continued securing of human progress but never at the price of human freedom.

References

American Civil Liberties Union (1999). DNA Testing ACLU Q&A. The ACLU Public Education Department. Retrieved May 21, 2003, from http://www.aclu-mass.org/ privacy/dnaqna.html

Health Insurance Portability and Accountability Act of 1996. Retrieved June 6, 2003, from http://www.hhs.gov/ ocr/hipaa

Human Research Protection Program (1996). Issues on DNA and Informed Consent. Human Protection Program University of California, San Diego. Retrieved May 27, 2003, from http://irb.ucsd.edu/ DNA_issues.pdf

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. (1979). The Belmont Report. Retrieved May 29, 2003, from http://ohrp.osophs.dhhs.gov/irb/ irb_introduction.htm

National DNA data Bank Advisory Committee (2002). The Privacy Implications of Forensic DNA Analysis. Royal Canadian Mounted Police. Retrieved from http://www.rcmpgrc.gc.ca/dna_ac/privacy_e.htm

The Nuremberg Code. (1947). Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law, 2(10), 181-182. Washington, D.C.: U.S. Government Printing Office

Protection of Human Subjects, 45 CFR 46. (2001). Retrieved May 29, 2003, from http://ohrp.osophs.dhhs.gov/ humansubjects/guidance/45cfr46.htm

Rooker, Kristina (2000). DNA and Privacy. The Impact of DNA Databases on Privacy. The University of Dayton School of Law. Retrieved May 22, 2002, from http://academic.udayton.edu/health/ 05bioethics/00rooker.htm

Rothstein, Mark A. Limiting the intrusiveness of Forensic DNA Sampling. The University of Houston School of Law. Retrieved June 23, 2003, from http://www.law.uh.edu/ healthlawperspectives/Privacy/ 990831DNA.html

Rudin, N. & Inman, K. (2001). An Introduction to Forensic DNA Analysis(2nd ed.). London: CRC Press.

Waak, E. (2002). The global reach of privacy invasion. The Humanist Online, 62, November/December 2002. Retrieved June 22, 2003, from http://www. thehumanist.org/humanist/articles/waak ND02.htm

Wines, Candi (2002). Genetic Privacy Legislation and Genetic Research in Oregon. Retrieved May 30, 2003, from http://www.doh.wa.gov/sboh/Priorities/ genetics/GTF2002 02-25/ Tab08-GeneticPrivacyPP.pdf

Authors' Note: This article was adapted from Vaughan Caines, Confidentiality, Privacy and Respect for Persons as Challenge-Horizons in Forensic DNA Research, a paper published in the 2003 Symposium Proceedings for the Annual Meeting of the Society of Research Administrators International, Pittsburgh, P& 19-22 October 2003. Disclaimer: The opinions in this paper are those of the authors and do not reflect the official policy of the State of New Hampshire Department of Health and Human Services, the Department of the Navy, the Department of Defense, or the United States Government. Contact: Mr. Vaughan Caines, Forensic Toxicologist, State of New Hampshire Public Health Laboratories, 6 Hazen Drive, Concord, New Hampshire 03301. Email: vcaines@.dhhs.state.nh.us.

Vaughan Caines, M.Sc.

Department of Health and Human Services

State of New Hampshire

Edward F. Gabriele, D.Min.

Office of Professional Integrity and Ethics

Navy Medicine