U. S. SENATE BILL 422:
THE GENETIC CONFIDENTIALITY
AND NON-DISCRIMINATION ACT OF 1997
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.
THE END OF ANONYMITY.
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.
"Research, involving the collection or study of existing
data, documents, records, pathological specimens, or
diagnostic specimens, if these sources are publicly available
or if the information is recorded by the investigator in such
a manner that subjects cannot be identified, directly or
through identifiers linked to the subjects."
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
From the researcher's perspective, anonymized tissues and data
make it impossible to validate research results. When the unique
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
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'
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.
(a) WRITTEN AUTHORIZATION- To be valid, the authorization by
an individual required by sections 101 (for collection of a DNA
sample) and 102 (for storage and genetic analysis of a DNA sample)
shall comply with each of the following:
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.
(1) WRITING- The authorization shall be in writing, signed by the
individual, and dated on the date of the signature.
(2) IDENTIFICATION OF COLLECTOR- The authorization shall identify
the person authorized to collect the DNA sample.
(3) DESCRIPTION OF COLLECTION- The authorization shall state the
tissue to be collected and the method of collection.
(4) AUTHORIZED USE- The authorization shall include a description
of all authorized uses of the DNA sample.
(5) STATEMENT REGARDING STORAGE AFTER COMPLETION OF ANALYSIS-
The authorization shall indicate whether the individual permits
the sample to be retained after the analysis is completed.
(6) STATEMENT REGARDING USES OF DNA SAMPLES FOR RESEARCH OR COMMERCIAL
PURPOSES- The authorization shall include provisions that permit the
individual to consent to--
(A) use of the DNA sample for research;
(B) commercial use of the DNA sample, with a waiver of, or a
provision for, economic benefit to the individual;
(C) if the individual consents to use under subparagraph (A) or (B),
use without identifiers, or use with individual identifiers or codes
retained, of the DNA sample; and
(D) notification, if individual identifiers or codes are retained,
about information resulting from such use that may have implications
for the individual or a family member of the individual.
(7) ADDITIONAL LAWS. The authorization shall comply with additional provisions of
Federal or State law requiring informed consent by human subjects in research,
including the provisions of part 46 of title 45, Code of Federal Regulations
(or any corresponding similar regulation or ruling).
(b) RETENTION OF AUTHORIZATION. The authorization shall be retained for the
period during which the DNA sample is stored.
(c). COPY. A copy of the completed authorization shall be provided to the
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--
(1) use of DNA samples is essential to the research project;
(2) the potential benefit of the research project to society
outweighs the potential risks to the research subjects, including
psychosocial risks and intrusion into the privacy of the subjects
that would result from genetic analysis of DNA samples; and
(3) the research protocol--
(A) contains adequate safeguards to protect against disclosure
of genetic information that is generated by the research;
(B) requires that research subjects will be given the applicable
information required under section 101;
(C) requires informed consent by the subjects, as provided in part
46 of title 45, Code of Federal Regulations (or any corresponding
similar regulation or ruling);
(D) requires the written authorization of the subjects, that
complies with the applicable requirements of section 301, and
that describes the protocol and the intended uses of the DNA
(E) prohibits inclusion of specific molecular genetic genotype
information in clinical records unless the subjects authorize
such inclusion in writing;
(F) with respect to protocols involving the use of DNA samples
from subjects deceased prior to the effective date of this Act--
(i) provides a reasonable method for disclosing to the family
members of a subject, the risks that--
(I) are associated with genetic information of the subject
that is generated by the research; and
(II) in reasonable medical judgment can be effectively
ameliorated, prevented, or treated;
(ii) takes into account the right of family members to refuse
learning about the genetic information; and
(G) describes the availability, or lack of availability, of genetic counseling related to the research project.
CASE EXAMPLE: INTERNET AUTOPSY DATABASE.
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
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).
(6) DNA SAMPLE- The term `DNA sample' means a human tissue sample
from which DNA is intended to be extracted, or DNA extracted from
such tissue sample. The term `DNA sample' does not include a tissue
sample that is taken--
(A) as a biopsy or an autopsy specimen, or as a clinical specimen
solely for the purpose of conducting an immediate clinical or diagnostic
test that is not a DNA test;
(B) as a blood sample solely for blood banking; or
(C) as a newborn screening specimen solely for determination of
disease in the newborn, as required by law.
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:
(F) with respect to protocols involving the use of DNA samples from
subjects deceased prior to the effective date of this Act--
(i) provides a reasonable method for disclosing to the family
members of a subject, the risks that--
(I) are associated with genetic information of the subject that
is generated by the research; and
(II) in reasonable medical judgment can be effectively ameliorated,
prevented, or treated; and
(ii) takes into account the right of family members to refuse
learning about the genetic information;
Section 503 states:
(a) IN GENERAL- A DNA sample collected prior to the effective date
of this Act may be analyzed as part of a research project under a
protocol approved by the Institutional Review Board, unless the
individual involved, within 3 years of the effective date of this Act,
submits a written request that such sample be withdrawn or destroyed;
(b) DISCLOSURE- Except as provided under section 502, genetic information
collected as part of a research project described in subsection (a)
may be disclosed only with the authorization of the individual involved
or the individual's legal representative.
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
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.
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.
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.
Berman JJ, Moore GW, Hutchins GM. Internet Autopsy Database.
Human Pathology 28:393-394, 1997
U. S. Code of Federal Regulations, 45 CFR Subtitle A
(10-1-95 Edition), part 46.101 (b) (4).
U. S. Senate 1416, H.R. 2690. The Genetic Privacy and
Non-Discrimination Act of 1995. November 15, 1995 (Senate);
November 29, 1995 (H.R.).
U. S. Senate 1360. The Medical Records Confidentiality
Act of 1995. October 24, 1995.
U. S. Senate 1898. The Genetic Confidentiality and
Non-Discrimination Act of 1996. June 24, 1996.
U. S. Senate Bill 422. The Genetic Confidentiality and
Non-Discrimination Act of 1997. March 11, 1997
The Hon. Pete Domenici, Senator (R, NM): 1-202-224-3121.