Jules J. Berman, Ph.D., M.D.
G. William Moore, M.D., Ph.D.
Grover M. Hutchins, M.D.

U. S. Government work published in: Diagn Mol Pathol. 1998 Aug;7(4):192-6.
PMID: 9917128; UI: 99114200.

      On March 11, 1997, Senator Pete Domenici introduced Senate Bill 422, the Genetic Confidentiality and Non-Discrimination Act of 1997. The bill specifies that "existing legal protections for genetic information are inadequate to ensure genetic privacy and to prevent genetic discrimination." The first designated purpose of the bill is: "To define the circumstances under which DNA samples may be collected, stored, and analyzed and genetic information may be collected, stored, analyzed and disclosed". The bill reinforces statutes already passed in 19 states that guarantee patients certain rights of control over their own personal genetic information. [Congressional Record, S2141]. This bill fundamentally changes the mechanism whereby molecular biologists acquire tissue, and defines new obligations between researchers and human subjects. Even if this bill, in its present form, is not passed, it appears inevitable that legislation with a similar intent will soon emerge. Any such legislation will carry the full weight and penalties of law. Because many current research practices may violate these proposed new regulations, researchers should understand the provisions of S. 422. Furthermore, it is crucial that researchers understand the bill now, before it becomes law, as this may be their last chance to lobby for any modifications to the bill.

      S. 422 is a thorough re-draft of S. 1898, the Genetic Confidentiality and Non-Discrimination Act of 1996, introduced on June 24, 1996. A copy of S. 422 can be obtained at the U.S. Government's Thomas Website (URL http://thomas.loc.gov/home/thomas.html, search under "Bill Text", 105th Congress, query word S. 422). The bill is a descendant from prior bills, related bills proposed to Congress, and numerous passed and drafted state laws that address the issue of genetic confidentiality (Appendix A). The new bill has been written with the help of a geneticist, Mary Kay Pelias. Dr. Pelias is currently a Legislative Fellow assigned to Senator Domenici's staff, and has helped write a thoroughly revised bill with added sections that specifically address the rights and responsibilities of researchers.

      One of the features of the new bill of greatest interest to researchers relates to the disappearance of the time-honored concept of "anonymized" tissue and data. Under current law (part 46 of title 45, Code of Federal Regulations), researchers who expunge all identifying links between patients and their tissue sample (or data), have no obligation to obtain informed consent. The practice of removing all links between a patient's data and the patient's identity has been referred to as "anonymization." It has been our experience that many researchers believe that anonymizing data is a fool-proof method for protecting the interests of both patient and researcher. Logic would seem to dictate that in an anonymized study, the patient would certainly be no worse off than if the study were not performed at all.

Nonetheless, ethicists have made some very cogent arguments against research using anonymized tissues or data. In our view, the most compelling argument against research using anonymized tissues arises in the instance in which life-saving information is discovered during the course of the research. Imagine the researcher's predicament when a treatable disease is diagnosed on an anonymized tissue sample. By definition, anonymized tissue samples have had all identifying links to the patient removed. There would be no way of identifying the patient who needs notification of research findings.

From the researcher's perspective, anonymized tissues and data make it impossible to validate research results. When the unique linkage between tissue (or data) and the patient is removed, there is no way of verifying data. In an anonymized database, one cannot be certain that the data haven't been biased by multiple submissions on a single patient. If there is a suspicion that a particular laboratory may have contaminated their contributions to the archive, there is no way of identifying those samples. Suppose particular data records are incomplete. Anonymized data do not permit the researcher to identify and contact a subject to verify or complete a data record. In the absence of any mechanism to verify data records, how can one accept the conclusions drawn from the data?

Studies that use anonymized data can deprive patients of certain entitlements that might be available to them if the study retained patient identifiers. For instance, if a person contributes a tissue that is used to create a commercially successful product, is that person entitled to some form of monetary reward?

Finally, patients may argue that certain avenues of research may affect them adversely, even when the study is anonymized. A person who suffers from a particular disease may not wish to contribute his/her DNA to research that may lead to a denial of insurance coverage to the class of patients with a similar disease. In this instance, a patient may suffer as a member of group of patients identified as the result of research done on an anonymized tissue sample.

For these reasons, it seems inevitable that the safe haven of "anonymized" tissue/data will fail against legal, ethical, and scientific objections. A new research paradigm is emerging in which researchers will pay scrupulous attention to issues of patient consent and confidentiality. In most cases, researchers will be required to maintain meticulous records that link a patient and patient's family to the disposition of tissues and data resulting from the researchers' studies.

S. 422 requires researchers and institutions to obtain consent for the acquisition and storage of DNA samples. S. 422 details the nature of consent, and the conditions of disclosure (of genetic information). The bill specifies the rights of the patient, including the right to withdraw his/her sample from studies even after consent has been granted. S. 422 calls for the host institution to become involved in the approval of studies through an Institutional Review Board organized in accordance with Section 46.102(g) of Title 45 Code of Federal Regulation. Documentation must be maintained so that patients and their family members can be linked with genetic information resulting from research studies. Consent forms must be written to specifications, signed, dated, with a copy provided to the patient, and stored by the researcher.

An example of some of the new requirements included in S. 422 is illustrated by Title III, Section 301, which specifies the written informed consent required for the collection and storage of a DNA sample. We suggest that a general authorization form, written in compliance with S. 422, could be written and provided to every patient at the time of admission. Writing an authorization form would require legal expertise. Compliance with paragraph D (regarding notification of patient and family) will require fastidious maintenance of records. Failure to comply to the letter of the law may result in considerable penalties. S. 422 endows patients with a Private Right of Action. in the event that researchers or institutions fail to comply with the bill. Title 7, Section 701 specifies that researches shall be liable to the individual for each such violation in an amount equal to any actual damages sustained as a result of the collection, storage, analysis or disclosure or $50,000, whichever is greater." If the violation is willful, or if profit or gain has resulted for the researcher, the penalties are much more severe! These penalties may have the regrettable effect of prompting researchers to seek and obtain "research malpractice" insurance.

Before any research is conducted, a number of specified conditions must be met, as described in Title 5, Section 501.

  • (a) CONDITIONS FOR GENETIC ANALYSIS- Except as provided in section 802(a), a DNA sample may be analyzed as part of a research project only if an Institutional Review Board, or similar board in the research industry, has determined that--

          The Internet Autopsy Database (IAD) is a novel Internet creation, introduced in November, 1995, and sponsored by The Johns Hopkins Medical Institutions Department of Pathology. The IAD can be visited on the World Wide Web at:


    The entire database is available to anyone in the world, and every record in the database can be downloaded. The IAD consists of over 49,000 abstracted autopsy records contributed by over a dozen medical institutions, and has been described in three recent publications (1-3).

    Because the IAD maintains a database of patient-related information, and because this data is offered to the public without restriction, compliance with pending legislation is a matter of great interest to the IAD board of directors. Furthermore, the IAD offers a method whereby archived pathology tissues can be distributed to researchers for purposes that may include genetic research on DNA extracted from tissue archives. The IAD autopsy tissue archives is a decentralized system, linking all the autopsy tissue blocks stored at the contributing institutions. None of the tissues were obtained or stored with informed consent specifying their inclusion in the IAD tissue archive, although we presume that each contributing hospital obtained legally valid permission to perform each autopsy.

    Patient identifiers have been removed by a brokered double encryption method that makes it impossible for any single person or institution to link a patient or institutional name with an IAD autopsy record.

    The mechanism follows: first, the contributing institution is asked to strip or encode patient identifiers from their submitted records. In this manner, the IAD administrator cannot know the identity of the patient. The IAD administrator then provides a new, encoded identifier for each record before the record is published on the IAD. The record that appears is anonymous to the institution that provided the autopsy, to the IAD administrator, and to anyone retrieving the autopsy record from the IAD Web page. If a researcher wishes to retrieve the tissue on a certain block, he/she must send an e-mail to the IAD administrator, identifying the IAD autopsy record of interest and his/her research objective. The IAD administrator decodes the record and restores the original encrypted record code provided by the contributing institution. The IAD administrator then forwards the institutionally coded record to the institution, along with the researcher's request. From this point on, the IAD administrator has no further role in the matter. The institution might decide to do nothing, preferring not to become involved in the researcher's project. Or, the contributing institution could use its institutional code to link back to the original patient autopsy number, retrieve the tissue block in question, and establish a collaboration with the researcher. Compliance with S. 422 and any other applicable laws regulating research, become the responsibility of the researcher and the institution providing tissue.

    It is important to note that in this scheme, a researcher can link a patient with a DNA sample only with the cooperation of four entities (the scientist, the IAD administrator, the institutional contributor (Institutional Review Board, IRB), and the patient's heirs and assigns.

    Does the IAD conform to regulations proposed in S. 422. First of all, the definition of tissue sample specified in S. 422 specifically excludes autopsy blocks (Section 3, Definitions).
    The exclusions of biopsy, autopsy, and specified clinical specimens are an important feature of the current version of the bill that was not present in the earlier bill. Without these exclusions, it would be impossible for pathology departments to continue their role as the archival repository for all tissues received on all patients biopsied or autopsied.

    The IAD indexes tissues collected over the past century. S. 422 deals with the problem of DNA samples and information derived prior to the effective date of S. 422 in two separate sections (Sec. 503 and 802). In addition, there are specific instructions for handling DNA samples derived from patients deceased prior to the effective date of the act (paragraph F, Sec. 501), as follows:

    It is tempting to assert that autopsy blocks are exempted from S. 422 regulations under the definition that excludes autopsy blocks as DNA samples. However, it seems arguable that once a researcher extracts DNA from an exempted autopsy tissue block, the extracted DNA becomes a valid DNA sample, and thus subject to the regulations of S. 422. If this were the case, then DNA samples obtained from ancient tissue blocks collected from autopsy archives would fall under Section 501 of S. 422. Hypothetically, the researcher using a 100 year old DNA sample would need to provide a reasonable method for disclosing any derived genetic information to the patient's descendants. The definition of "Family," specified in Section 3 of S. 422, is, "The term "family" means the biological and legal relatives of an individual who may have a material interest in the genetic information of the individual." If a genetic study is performed on a tissue block that is 100 years old, it would certainly be an imposing task to inform the extant family of the deceased of the results of the test. This family would consist of both biological and legal relatives. Section 501 of S. 422 does specify that the researcher must provide a "reasonable" method, and thus may refrain from "unreasonable" efforts to contact the deceased family, but the distinction between reasonable and unreasonable methods may differ from jurisdiction to jurisdiction. As the administrators of the IAD, we advise all prospective users of IAD tissue samples to resolve these issues via legal counsel and the consent of their own IRB.

          In summary, S. 422 is legislation of great importance to all molecular biologists. Senator Domenici has argued that without safeguards designed to eliminate the abuse of genetic information, the American public would be reticent to cooperate with researchers [Congressional Record, S2141]. In any event, it seems inevitable that researchers must accustom themselves to a new paradigm of confidentiality. We suspect that it will be several years before institutions develop guidelines that gain wide acceptance in research institutions throughout the country. Institutional guidelines of dealing with confidentiality and consent issues will have to withstand courtroom tests. Private individuals may seek relief in court (i.e., individuals will not need to wait for the attorney general to decide which cases should be prosecuted). In this case, thoughtful researchers who minsinterpret the law will be subject to harsh civil penalties (described in Title 7), provided as remedy to individuals. For this reason, it is very important for all researchers and institutional legal staff to understand all of the provisions of S. 422.

    1. Moore GW, Berman JJ, Hanzlick RL, Buchino JJ, Hutchins GM. A prototype international autopsy database: 1625 consecutive fetal and neonatal autopsy facesheets spanning twenty years. Arch Pathol Lab Med 120:782-785, 1996.

    2. Berman JJ, Moore GW, Hutchins GM. Maintaining patient confidentiality in the public domain internet autopsy database. J Amer Med Informatics Assn (JAMIA), Symposium Supplement, pp. 328-332, 1996.

    3. Berman JJ, Moore GW, Hutchins GM. Internet Autopsy Database. Human Pathology 28:393-394, 1997