**Ethical, Legal and Social Implications (ELSI) Research Advisors**

**Report to the National Advisory Council for Human Genome Research**

**February 2005**

**Introduction**

The ELSI Research Advisors (ERA) group was established in the Fall of
2000 to provide the National Advisory Council for Human Genome Research
(NACHGR) with advice concerning the ELSI Research Program. As part of
its mission, ERA is required periodically to report to the NACHGR on the
status of the ELSI Program. The group participated in the planning
process for the development of the AVision for the Future of Genomic
Research@ article (Vision Document) that was published in *Nature* in
April 2003[^1] and has been involved in helping the ELSI Program shape
new initiatives in response to the future directions for ELSI research
that were presented in the document. This report briefly summarizes the
ELSI Program=s progress since the Vision Document was published,
identifies some areas of concern regarding the future of ELSI research,
and argues for the importance of ELSI research for all components of the
National Institutes of Health (NIH) and the need to encourage other
parts of NIH to become involved in supporting this research.

**The ELSI Program since the Completion of the Human Sequence**

In the Vision Document, ELSI research issues are integrated throughout
the **Grand Challenges** (GC) laid out for each of the three floors of
genomic research: **Genomes to Biology, Genomes to Health and Genomes to
Society**. They are specifically included in **Genomes to Biology**
under GC I-5 regarding intellectual property issues. In **Genomes to
Health**, ELSI issues feature prominently in GC II-4 on the provision of
risk information in clinical settings and GC II-5 which focuses on
ensuring that the benefits of the genomic revolution are made available
to all. The third floor, **Genomes to Society**, focuses almost
exclusively on issues that are addressed by the ELSI Program, including
the development of policy options to ensure the safe use of genetic
information and technologies (GC III-1), the exploration of the issues
surrounding genetics and race and ethnicity (GC III-2), the genetics of
Anormal@ traits and behaviors (GC III-3), and the ethical boundaries of
genetic and genomic research (GC III-4). Following the publication of
the Vision Document, the ELSI Program revised its regular (R01) and
small (R03) research grant program announcements to incorporate these
new grand challenges. These new announcements were released in January
2004.

In the last few years, the ELSI Program has supported a number of
research initiatives in each of these areas. Within the **Genomes to
Biology** floor, in 2002 and 2003, ELSI funded a pilot survey by the
Kennedy Institute of Ethics and the Association of University Technology
Managers (AUTM) to gather information on the licensing practices and
policies of universities across North America. These data have been used
as a foundation for the deliberations of the Institute of Medicine=s
committee on AIntellectual Property Rights in Genomics and
Protein‑Related Research.@ In addition, in 2004, the ELSI Program issued
a new Request for Applications (RFA) to study the role of laws and
policies regarding intellectual property rights in genetics and genomics
research and development, and the effect of such laws and policies on
progress in these fields and on commercialization, drug development,
health care delivery, and the public health. These applications will be
reviewed and funded in Fiscal Year (FY) 2005.

Within the **Genomes to Health** area, the ELSI Program has continued to
fund a number of research projects focused on the safe and effective use
of genetic technologies and risk information in clinical settings (GC
II-4). These have included:

-   an ongoing study at Boston University (PI: RC Green) examining
    genetic risk assessment and counseling for Alzheimer disease[^2] and

-   a new study at the Fred Hutchinson Cancer Research Center (S Ramsey)
    to develop a framework for evaluating the clinical and economic
    tradeoffs associated with genetic testing for colon cancer.

The ELSI Program has also funded a number of studies examining
disparities in access to and use of genetic test information (GC II-5),
including:

-   an ongoing University of Pennsylvania study (K Armstrong) examining
    the impact of an individual=s level of distrust and the attributes
    of a genetic test and its delivery on willingness to undergo
    predictive genetic testing among African American, Latino and
    Caucasian populations[^3] and

-   a new study at the University of North Carolina (G Corbie-Smith)
    exploring the attitudes of African Americans and Caucasians
    regarding genetic research and colon cancer risk.

Within the **Genomes to Society** floor, the ELSI Program has funded a
number of studies developing data upon which research and social
policies can be based (GC III-1), including:

-   an ongoing study at the University of North Carolina (G Henderson)
    examining the social construction and communication of benefit in
    gene transfer research,[^4]

-   a study (co-funded with NIEHS) at Arizona State University (G
    Marchant) to evaluate the legal, ethical and policy implications of
    the application of genetic susceptibility data to environmental
    regulation, and

-   a new study by the American Society for Law, Medicine and Ethics (B
    Moulton) to investigate the issues surrounding DNA profiling and to
    educate policymakers so that they better understand privacy and
    civil liberty issues involved in the application of DNA technology
    to the criminal justice system.

The ELSI Program has funded 11 studies as the result of two ELSI genetic
variation RFAs[^5] and is currently supporting a consortium of 21
researchers who are looking at the issues surrounding genetic and
genomic research and race and ethnicity (GC III-2). These include:

-   ongoing studies such as the project at the University of Georgia (C
    Condit) exploring the feasibility of producing messages about human
    genetic variation that are non-discriminatory in their impact on
    public attitudes[^6] and

-   new studies such as the University of Pennsylvania project (P
    Sankar) examining why researchers use race and ethnicity in forensic
    and medical genetic research, and what researchers think are
    appropriate generalizations and applications of their findings.

The ELSI Program has funded a small number of projects examining the
issues surrounding the genetics of traits and behaviors (GC III-3),
including:

-   a study by the Hastings Center (E Parens) to develop tools and
    resources for open and informed public discussion about behavioral
    genetics[^7] and

-   a study by the University of Michigan (E Singer) exploring and
    analyzing public beliefs about genes and the environment as causes
    of behavior.[^8]

In the final **Genomes to Society** Grand Challenge that explores the
potential ethical boundaries of genetic and genomic research (III-4),
the ELSI Program has funded a substantial body of work by a team at Case
Western (E Juengst) examining the issues surrounding genetic
enhancement[^9] and a series of small research grants at the University
of Maryland (M Sagoff) analyzing the potential impact of genetic and
genomic technologies on concepts of humanity.[^10]

In addition to the Grand Challenges, the ELSI Program is currently
funding projects in four cross cutting areas: Education, Conferences,
Training and Resources. The largest portion of this cross cut funding is
currently devoted to Education projects, including:

-   an ongoing project at Dartmouth University and Howard University (RM
    Green) to prepare college and university faculty to develop and
    teach courses on ELSI and

-   a new project by SoundVision Inc. (B Scott) supporting the
    development of radio broadcasts on genetics and ELSI issues
    specifically targeted to minority populations.

However, in order to allow the ELSI Program to focus more attention on
funding research grants, at the recommendation of its advisors the NHGRI
has not reissued its education grant (R25) program announcement. The
Program will continue to fund education grants that are currently
obligated, but will gradually phase out that portion of the portfolio.
The ELSI Program will continue to fund conference grants, training
grants and a small number of resource grants.

Table 1 lists estimated budget totals for FY 2004 in each Grand
Challenge and Crosscut area.

  ------------------------------------------------------- ---------------
  **Table 1. FY 2004 Estimated ELSI Totals by Grand       
  Challenge**                                             

  **Grand Challenge**                                     **FY 2004
                                                          Total**

  I-5. Intellectual property                              \$699,113

  II-4. Genetic Risk Information in Health Care           \$7,551,419

  II-5. The Health of All                                 \$1,173,074

  III-1. Policy Options for the Use of Genetic            \$2,898,860
  Information                                             

  III-2. Genetics, Race and Ethnicity                     \$1,786,814

  III-3. Genetics and Normal Traits/Behaviors             \$489,985

  III-4. Boundaries of Genetic Research                   \$74,250

  **Crosscut**                                            

  Crosscut 1: Education                                   \$2,958,820

  Crosscut 2: Conferences                                 \$139,666

  Crosscut 3: Training                                    \$200,000

  Crosscut 4: Resources                                   \$527,077

  **FY 2004 ELSI Total**                                  \$18,499,078
  ------------------------------------------------------- ---------------

**Persistent Challenges Faced by the ELSI Research Program**

The ELSI Program has been the subject of many critical assessments since
its inception. These have ranged from focused analyses by science policy
or ethics scholars to more in-depth, formal evaluations by panels of
experts and advisors^.^[^11]^,^[^12]^,^ [^13]^,^[^14] The most recent
evaluation was completed in 2000 by the ELSI Research Planning and
Evaluation Group (ERPEG). This group issued a report in January 2001
which included a series of recommendations to strengthen the
Program.^14^ More recently as part of the April 2003 planning process,
the ELSI Research Advisors, working with an ad hoc policy group,
published a brief white paper examining the "Role of ELSI Research in
the Future of Genomics Research."[^15] This paper was used in the
development of the Vision Document and provided the ELSI Program with
specific recommendations to enhance ELSI research following the
completion of the sequence.

Several recurrent concerns have been raised in each of these reports
about the ability of the ELSI Program to fulfill its mission to
anticipate and address the implications of genetic and genomic research.
These include:

-   The need for increased integration between ELSI and genetic and
    genomic research,

-   The need for the more effective translation of ELSI research
    findings to accessible products that can inform policy
    deliberations, and

-   The need to support the continued expansion of the disciplinary and
    demographic diversity of the ELSI community of researchers.

The first concern is an acknowledgement of the fact that in order for
ELSI research to be relevant, it must be grounded in cutting edge
genetic and genomic research, and in order for this to occur, there must
be close communication and collaboration between the two research
communities. While there has been a general strengthening of the
communication between genetic and genomic and ELSI researchers over the
years, there has not been the kind of sustained collaboration that is
needed to ensure the ongoing timeliness and relevance of ELSI research.
This may be due in part to a conflict inherent in the establishment of
the ELSI Program within the larger Human Genome Project. On the one
hand, ELSI researchers have questioned whether the ELSI Program can
maintain its ability to critically analyze the implications of genetic
and genomic research when its funding is overseen by the same
individuals who are responsible for the successful implementation of
this research. On the other hand, genetic and genomic researchers often
conflate the scholarly examinations of the implications of genetic and
genomic research funded by the ELSI Program with the development and
enforcement of human subjects research regulations which are actually
developed and overseen by regulatory bodies like the Federal Office for
Human Research Protections (OHRP). Thus, some ELSI researchers tend to
be uneasy about the potential for the genetic and genomic research
community to unduly constrain ELSI research and some genetic and genomic
researchers tend to view ELSI as trying to slow down the research
enterprise with unnecessary ethical hurdles and regulations. This
somewhat natural, if misdirected, antipathy, coupled with a lack of
systemic recognition and support for this kind of cross-disciplinary
research within the academic and Federal research funding communities,
has made collaborations between these researchers somewhat tenuous and
difficult to sustain.

The second concern goes to the fundamental fact that the ELSI Program is
capable of producing a great deal of informative and relevant data, but
that these data may not be presented in a form that is accessible to
research, health and social policy makers. As a result, it is difficult
to assure that ELSI findings are considered in the development of
policies that address the implications of genetic and genomic research.
While the ELSI Program has funded projects and convened meetings that
have resulted in the development of policy options and standard of care
recommendations,[^16] and ELSI publications have been cited in the
development of policies and legislation, as an extramural research
program housed within the Federal Government, ELSI is statutorily Anot
capable of developing or presenting in an effective manner specific
policy recommendations to the Nation, the Congress, or the executive
branch on the full range of problems presented by the Human Genome
Project.@[^17]

Over the years, the task of developing and presenting these
recommendations has fallen to a variety of organizations, including the
original ELSI Working Group (1990-1996), the ongoing Trans-NIH Bioethics
Committee, the Secretary=s Advisory Committee on Genetic Testing (SACGT)
and its successor the current Secretary=s Advisory Committee on
Genetics, Health and Society (SACGHS) and the National Bioethics
Advisory Committee and its successor the Presidents Bioethics
Commission. While these groups have made use of ELSI research data in
the development of policies and standards of care, none of them have
been conversant enough with the totality of ELSI research to effectively
and consistently translate the findings from this research to the
various policy making communities, and, of equal importance, provide
feedback to ELSI researchers regarding the data needs of these
communities.

The final concern speaks to the need for the ELSI research community to
continue to expand its range of expertise in order to maintain its
ability to respond effectively to rapidly emerging scientific advances
and concomitant policy needs. This requires not only the continual
recruitment of individuals from different disciplines and demographic
backgrounds into ELSI research, but an ongoing effort to train the next
generation of researchers. The ELSI Program has been very successful in
establishing a new field of research and a research community with great
strength and depth of expertise, as indicated by the increasing number
of competitive continuations of ongoing grants (several of which are
cited above) and the frequent recruitment of ELSI researchers to provide
expert testimony or to serve on advisory groups. However, it has not
been as successful in supporting the recruitment and training of new
investigators from disciplines and communities not currently well
represented in the ELSI research community. While many factors may be
contributing to this, one of the most obvious is the small number of
well-established research programs focused on ELSI research that can
provide the incentives for multi-disciplinary work and the
infrastructure to support the cross disciplinary training of new

investigators.

**The ELSI Centers Program**

In response to these concerns and on the recommendations of its
advisors, the ELSI Program issued a call for applications for the
development of Centers of Excellence in ELSI Research (CEERs). The
purpose of these CEERs is to encourage the development of broadly
multidisciplinary research teams that can not only rapidly identify and
respond to emerging issues, but also use the full spectrum of research
and consensus building methodologies to translate the findings of ELSI
research to useful policy and practice options. The three overarching
goals of the program are to:

-   Transcend the boundaries between genetic and genomic research and
    ELSI research;

-   Translate ELSI research to safe, effective and just genetic and
    genomic policies and practices in research, health and non-medical
    settings; and

-   Train the next generation of ELSI researchers to ensure disciplinary
    and demographic diversity.

In September 2004, four full centers and three exploratory centers were
funded. The first meeting of the researchers was held in February 2005.
All of the funded CEER grants address issues highlighted in the Vision
Document.

-   The Duke center (B Cook-Deegan) proposes to explore the impact of
    publication, data and materials-sharing, patenting, database
    protection, and other practices that affect information flow in
    genomics research.

-   The University of Washington center (W Burke) focuses on the
    clinical integration of genetic technologies and information for
    medically underserved communities, taking into consideration diverse
    voices that have often not been previously heard.

-   The Case Western center (E Juengst) proposes to address issues
    related to genomics and genetics research, including
    commercialization, race and ethnicity, normal traits, and genetic
    enhancement.

-   The Stanford center (M Cho) focuses on developing models for
    integrating ELSI concerns into neuro- and behavioral genetics
    research.

-   The University of North Carolina exploratory center (D Bailey)
    focuses on the issues around the design and conduct of large sample
    gene discovery and disclosure studies.

-   The Georgetown exploratory center (A Shields) is focused on health
    disparities.

-   The Howard exploratory center (C. Royal) will explore the genomic
    and social identity issues surrounding the African Diaspora.

A CEERs Advisory Group (CAG) is being established to provide expert
input on the individual Centers and on the CEERs program as a whole. For
individual CEER evaluations, a site visit will take place in the third
year to determine whether the Center is successfully meeting its
individual goals and should continue to receive full funding and be
invited to submit a competitive renewal; or is not meeting its goals and
should begin to be phased out in its fourth year. For the CEERs program
evaluation, the CAG will participate in determining whether the program
as a whole is successfully accomplishing the three broad goals outlined
above.

**Program Evaluation**

Just as the evaluation of the individual CEERs and the overall CEERs
program is crucial, it will be important for the ELSI Program to
continue to evaluate its effectiveness in anticipating and addressing
the implications of genetic and genomic research more broadly. It will
be essential that the Program initiate a vigorous discussion of how to
define endpoints and metrics for measuring successful ELSI research. For
example, what are the relative merits of using the citation of ELSI
publications in peer reviewed literature, in state and federal
legislation, and in the development of standard of care guidelines as
measures of success? The three broad goals set out for the CEERs program
can be used as a starting point for this discussion, but ultimately they
will need to be expanded and refined to more fully encompass the depth
and breadth of ELSI activities. In addition to determining endpoints,
the evaluation should focus on three levels of analysis: 1) the Project
Level to determine whether individual projects are meeting their
specific aims; 2) the Program Level to determine whether the ELSI
Program as a whole is meeting its goals; and 3) Program Balance to
determine the combination of study topics, funding mechanisms and types
of projects that are most effective in accomplishing the program=s
mission. This last level of evaluation will be particularly critical if
the CEERs program moves forward as currently envisioned, consuming an
increasing percentage of the ELSI budget set aside. Table 2 provides a
projection of the percentage of the ELSI budget that will be devoted to
the CEERs program through FY 2009.

+------------+---+-------+-------+--------+--------+--------+--------+
| **Table 2. |   |       |       |        |        |        |        |
| CEER       |   |       |       |        |        |        |        |
| OUTYEAR    |   |       |       |        |        |        |        |
| TOTAL      |   |       |       |        |        |        |        |
| BUDGET     |   |       |       |        |        |        |        |
| PRO        |   |       |       |        |        |        |        |
| JECTIONS** |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
|            |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **Center   |   | **FY2 | **FY  | **FY   | **FY   | **FY   | ***FY  |
| PI**       |   | 004** | 2     | 2006** | 2007** | 2008** | 2009   |
|            |   |       | 005** |        |        |        | ^1^*** |
+------------+---+-------+-------+--------+--------+--------+--------+
|            |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **BAILEY** | * | \$21  | \$21  | \$0    | \$0    | \$0    | *\$0*  |
|            | * | 4,634 | 4,503 |        |        |        |        |
|            | P |       |       |        |        |        |        |
|            | 2 |       |       |        |        |        |        |
|            | 0 |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| *          | * | \$18  | \$18  | \$1    | \$0    | \$0    | *\$0*  |
| *SHIELDS** | * | 7,799 | 7,763 | 93,396 |        |        |        |
|            | P |       |       |        |        |        |        |
|            | 2 |       |       |        |        |        |        |
|            | 0 |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **ROYAL**  | * | \$22  | \$22  | \$2    | \$0    | \$0    | *\$0*  |
|            | * | 0,091 | 5,173 | 31,926 |        |        |        |
|            | P |       |       |        |        |        |        |
|            | 2 |       |       |        |        |        |        |
|            | 0 |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| *          | * | \$90  | \     | \$1,0  | \$1,1  | \$1,1  | *      |
| *JUENGST** | * | 5,664 | $1,04 | 75,892 | 31,308 | 53,867 | \$1,18 |
|            | P |       | 0,969 |        |        |        | 8,483* |
|            | 5 |       |       |        |        |        |        |
|            | 0 |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **BURKE**  | * | \$91  | \$90  | \$9    | \$9    | \$9    | *      |
|            | * | 1,748 | 0,847 | 11,568 | 38,767 | 81,672 | \$1,01 |
|            | P |       |       |        |        |        | 1,122* |
|            | 5 |       |       |        |        |        |        |
|            | 0 |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **CHO**    | * | \$68  | \$80  | \$8    | \$8    | \$7    | *\$80  |
|            | * | 9,985 | 3,537 | 27,201 | 52,013 | 81,129 | 4,563* |
|            | P |       |       |        |        |        |        |
|            | 5 |       |       |        |        |        |        |
|            | 0 |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **CO       | * | \$94  | \$97  | \$1,0  | \$1,0  | \$1,0  | *      |
| OKDEEGAN** | * | 9,113 | 5,766 | 04,188 | 34,917 | 66,023 | \$1,09 |
|            | P |       |       |        |        |        | 8,004* |
|            | 5 |       |       |        |        |        |        |
|            | 0 |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **TOTAL    |   | \     | \     | \$4,2  | \$3,9  | \$3,9  | *      |
| ^2^**      |   | $4,07 | $4,34 | 44,171 | 57,005 | 82,691 | \$4,10 |
|            |   | 9,034 | 8,558 |        |        |        | 2,172* |
+------------+---+-------+-------+--------+--------+--------+--------+
|            |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **ELSI     |   | **\$3 | **\$3 | **\    | **\    | **\    | ***\$  |
| Total**    |   | ,454, | ,723, | $4,194 | $3,907 | $3,932 | 4,052, |
|            |   | 034** | 558** | ,171** | ,005** | ,691** | 172*** |
+------------+---+-------+-------+--------+--------+--------+--------+
|            |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| ***Reissue |   |       |       | *      | *      | *      | *      |
| @ \$3M in  |   |       |       | \$3,00 | \$3,09 | \$6,18 | \$6,36 |
| 06 and     |   |       |       | 0,000* | 0,000* | 2,700* | 8,181* |
| 08***      |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
|            |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **ELSI Set | * | **18  | **18  | \$18,9 | \$19,3 | **\$   | ***\$2 |
| Aside      | * | ,499, | ,559, | 30,384 | 08,992 | 19,695 | 0,089, |
| ^3^**      |   | 078** | 200** |        |        | ,172** | 075*** |
|            | * |       |       |        |        |        |        |
|            | * |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **% of     |   | **18  | **20  | **3    | **3    | **5    | ***51  |
| ELSI Total |   | .7%** | .1%** | 8.0%** | 6.2%** | 1.4%** | .9%*** |
| ^4,5^**    |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
|            |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **^1^** FY |   |       |       |        |        |        |        |
| 2009       |   |       |       |        |        |        |        |
| Estimate   |   |       |       |        |        |        |        |
| assumes    |   |       |       |        |        |        |        |
| c          |   |       |       |        |        |        |        |
| ompetitive |   |       |       |        |        |        |        |
| renewals   |   |       |       |        |        |        |        |
| of         |   |       |       |        |        |        |        |
| existing   |   |       |       |        |        |        |        |
| P50s are   |   |       |       |        |        |        |        |
| s          |   |       |       |        |        |        |        |
| uccessful. |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **^2^**    |   |       |       |        |        |        |        |
| Budget     |   |       |       |        |        |        |        |
| Figures    |   |       |       |        |        |        |        |
| reflect    |   |       |       |        |        |        |        |
| TOTAL      |   |       |       |        |        |        |        |
| Center     |   |       |       |        |        |        |        |
| budgets    |   |       |       |        |        |        |        |
| (i.e.,     |   |       |       |        |        |        |        |
| ELSI       |   |       |       |        |        |        |        |
| budget     |   |       |       |        |        |        |        |
| con        |   |       |       |        |        |        |        |
| tributions |   |       |       |        |        |        |        |
| plus       |   |       |       |        |        |        |        |
| co-funding |   |       |       |        |        |        |        |
| from DOE   |   |       |       |        |        |        |        |
| and NICHD) |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **^3^**    |   |       |       |        |        |        |        |
| Based on   |   |       |       |        |        |        |        |
| projected  |   |       |       |        |        |        |        |
| 2% annual  |   |       |       |        |        |        |        |
| increase   |   |       |       |        |        |        |        |
| from FY    |   |       |       |        |        |        |        |
| 2005 base. |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **^4^**    |   |       |       |        |        |        |        |
| P          |   |       |       |        |        |        |        |
| ercentages |   |       |       |        |        |        |        |
| are based  |   |       |       |        |        |        |        |
| only on    |   |       |       |        |        |        |        |
| NHGRI ELSI |   |       |       |        |        |        |        |
| con        |   |       |       |        |        |        |        |
| tributions |   |       |       |        |        |        |        |
| and do not |   |       |       |        |        |        |        |
| include    |   |       |       |        |        |        |        |
| additional |   |       |       |        |        |        |        |
| co-funding |   |       |       |        |        |        |        |
| from DOE   |   |       |       |        |        |        |        |
| and NICHD  |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+
| **^5^**    |   |       |       |        |        |        |        |
| The jump   |   |       |       |        |        |        |        |
| in % of    |   |       |       |        |        |        |        |
| ELSI Total |   |       |       |        |        |        |        |
| in FY 2006 |   |       |       |        |        |        |        |
| is due to  |   |       |       |        |        |        |        |
| the fact   |   |       |       |        |        |        |        |
| that DOE   |   |       |       |        |        |        |        |
| was unable |   |       |       |        |        |        |        |
| to commit  |   |       |       |        |        |        |        |
| co-funding |   |       |       |        |        |        |        |
| to Cho and |   |       |       |        |        |        |        |
| CookDeegan |   |       |       |        |        |        |        |
|            |   |       |       |        |        |        |        |
| Beyond FY  |   |       |       |        |        |        |        |
| 2005, but  |   |       |       |        |        |        |        |
| may        |   |       |       |        |        |        |        |
| continue   |   |       |       |        |        |        |        |
| cont       |   |       |       |        |        |        |        |
| ributions, |   |       |       |        |        |        |        |
| if funds   |   |       |       |        |        |        |        |
| are        |   |       |       |        |        |        |        |
| available. |   |       |       |        |        |        |        |
+------------+---+-------+-------+--------+--------+--------+--------+

**Concerns for the Future of ELSI Research**

With the long term commitment of funds to the new CEER grants, the
current climate of no-growth federal budgets, and the continuing
inflation of grant budgets across NIH, the ELSI Program has entered a
new era of budget constraints. As in many agencies, the shortage of
funds is already having an impact on the amount of the budget that can
be spent on new investigator initiated research grants (less than 14.5%
of the ELSI budget in 2005). Table 3 provides a brief summary of the
downward trend since 2000 and the noticeable drop off over the last
year. While this drop in funding for investigator initiated research is
of concern, it is a not unexpected trade off caused in part by the
creation of the CEERs program. Of perhaps greater concern is the impact
that shrinking budgets will have on the ability of the ELSI Program to
expand the diversity of its research portfolio and on its ability to
provide support for new investigators from under represented groups and
from disciplines in the law and humanities, who traditionally do not
fare well in the NIH peer review system.

<table>
<colgroup>
<col style="width: 16%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 13%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="12"><p><strong>TABLE 3. Percent New and Total ELSI
Expenditures by Research Mechanism</strong></p>
<p><strong>FY 2000- 2005</strong></p></td>
</tr>
<tr class="even">
<td><strong>FISCAL YEAR</strong></td>
<td colspan="2"><strong>FY 2000</strong></td>
<td colspan="2"><strong>FY 2001</strong></td>
<td colspan="2"><strong>FY 2002</strong></td>
<td colspan="2"><strong>FY 2003</strong></td>
<td colspan="2"><strong>FY 2004</strong></td>
<td><strong>FY 2005 Est.</strong></td>
</tr>
<tr class="odd">
<td><strong>TOTAL ELSI</strong></td>
<td colspan="2">$13,269,458</td>
<td colspan="2">$15,006,647</td>
<td colspan="2">$16,767,016</td>
<td colspan="2">$18,023,110</td>
<td colspan="2">$18,499,078</td>
<td>18,559,200</td>
</tr>
<tr class="even">
<td><strong>Percent Increase</strong></td>
<td colspan="2">20.32%</td>
<td colspan="2">11.68%</td>
<td colspan="2">10.53%</td>
<td colspan="2">6.07%</td>
<td colspan="2">2.57%</td>
<td>0.33%</td>
</tr>
<tr class="odd">
<td></td>
<td><strong>New</strong></td>
<td><strong>Total</strong></td>
<td><strong>New</strong></td>
<td><strong>Total</strong></td>
<td><strong>New</strong></td>
<td><strong>Total</strong></td>
<td><strong>New</strong></td>
<td><strong>Total</strong></td>
<td><strong>New</strong></td>
<td><strong>Total</strong></td>
<td><strong>Total Commit.</strong></td>
</tr>
<tr class="even">
<td><strong>Centers (p20/50)</strong></td>
<td></td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>18.67%</td>
<td>18.67%</td>
<td>20.06%</td>
</tr>
<tr class="odd">
<td><strong>Regular (R01)</strong></td>
<td>25.01%</td>
<td>70.31%</td>
<td>19.26%</td>
<td>62.98%</td>
<td>13.38%</td>
<td>47.08%</td>
<td>32.99%</td>
<td>58.58%</td>
<td>6.75%</td>
<td>49.90%</td>
<td>47.83%</td>
</tr>
<tr class="even">
<td><strong>Small (R03)</strong></td>
<td>0</td>
<td>0</td>
<td>0.48%</td>
<td>0.48%</td>
<td>2.84%</td>
<td>3.27%</td>
<td>2.39%</td>
<td>4.61%</td>
<td>0.40%</td>
<td>2.36%</td>
<td>2.57%</td>
</tr>
<tr class="odd">
<td><strong>Education (R25)</strong></td>
<td>9.69%</td>
<td>12.26%</td>
<td>7.82%</td>
<td>12.58%</td>
<td>7.20%</td>
<td>17.34%</td>
<td>8.94%</td>
<td>14.75%</td>
<td>1.01%</td>
<td>13.92%</td>
<td>11.58%</td>
</tr>
<tr class="even">
<td><strong>Resources (P41)</strong></td>
<td>3.17%</td>
<td>3.17%</td>
<td>0</td>
<td>3.02%</td>
<td>5.96%</td>
<td>8.47%</td>
<td>0</td>
<td>2.40%</td>
<td>0</td>
<td>2.41%</td>
<td>0</td>
</tr>
<tr class="odd">
<td><strong>Other (IAAs, Mtgs., Training, etc.)</strong></td>
<td>14.04%</td>
<td>14.26%</td>
<td>10.08%</td>
<td>20.94%</td>
<td>11.26%</td>
<td>23.85%</td>
<td>6.47%</td>
<td>19.66%</td>
<td>0.49%</td>
<td>12.73%</td>
<td>3.47%</td>
</tr>
<tr class="even">
<td><strong>Percent Total</strong></td>
<td>51.91%</td>
<td>100%</td>
<td>37.65%</td>
<td>100%</td>
<td>40.65%</td>
<td>100%</td>
<td>50.79%</td>
<td>100%</td>
<td>27.32%</td>
<td>100%</td>
<td>85.51%</td>
</tr>
</tbody>
</table>

**ELSI Research as an NIH-wide Priority**

Given these concerns and the low likelihood that additional funds will
be made available to NHGRI in the near future, the base for funding of
ELSI research must be expanded more broadly across the NIH. As a part of
the HGP, the ELSI Program=s mission has focused specifically on the
implications of genetic and genomic research, but the basic ethical,
legal and social issues raised by the HGP apply much more broadly to all
rapidly evolving biomedical technologies and research fields, such as
nanomedicine, anti-aging medicine and xeno-transplantation, as well as
traditional biomedical and behavioral research involving racially and
ethnically identified populations, children, the cognitively impaired
and research focused on normal traits and behaviors like aging,
intelligence and aggression.

Ten NIH Institutes signed on to the ELSI program announcements in 2004,
and several also participated in the 1999 and 2003 ELSI Genetic
Variation RFAs and research consortia, and the 1994 Cancer Genetic
Studies and 1991 CF Genetic Studies RFAs and research consortia. While
this record of participation by individual institutes indicates an
underlying level of interest in ELSI research, it does not represent a
strong institutional commitment by the NIH. For example, since 1999 the
NIH has supported three NIH-wide program announcements calling for
research (R01), training (T15) and career development (K01) applications
that address the ethical issues surrounding research involving human
participants. These announcements were part of the Federal initiative
developed as part of the President=s 1997 apology for the U.S.
Government=s support for the Tuskegee experiments and were intended to
emphasize NIH support for ethics training and research. While these
NIH-wide program announcements have resulted in a number of productive
grants, the T15 and K01 announcements, which have already expired, have
not been reissued, and the R01 announcement, which was due to expire in
May 2005, was only recently extended for a single year while a decision
is made whether it should be continued.

Recently, the NIH has launched two new trans-NIH initiatives: The
Roadmap and the Public Trust Initiative. While ethics research is not
currently incorporated into either initiative, the implementation of
these initiatives may create a unique opportunity for the NHGRI and the
NACHGR to encourage other institutes, and NIH as a whole, to make a more
sustained NIH-wide commitment to supporting this type of research.

The Roadmap was launched in 2004 as a series of NIH-wide initiatives
designed to Atransform our new scientific knowledge into tangible
benefits for people.@ It focuses on three themes.

-   The 1^st^ themeBNew Pathways to DiscoveryBis designed in part to
    Afully capitalize on the recent completion of the human genome
    sequence and many recent discoveries in molecular and cell biology@
    by ensuring Awide access to technologies, databases and other
    scientific resources that are more sensitive, more robust, and more
    easily adaptable to researchers\' individual needs.@

-   The 2^nd^ themeBResearch Teams for the FutureBencourages the
    promotion of interdisciplinary research teams and new approaches to
    team-based research.

-   The 3^rd^ ThemeBRe-engineering the Clinical Research
    EnterpriseBpromotes the harmonization of clinical research
    regulatory processes and the development of enhanced infrastructures
    and more efficient mechanisms to translate basic research findings
    to clinical research settings. AA major goal of this initiative is
    to more fully involve and empower the public in the research
    process.@ [^18]

Recognizing the importance of the public=s role in ensuring the success
of biomedical research, after the initiation of the Roadmap the NIH
Director established the NIH Public Trust Initiative (PTI) as an
important adjunct to the Roadmap. The mission of the PTI is Ato promote
activities and attitudes that foster understanding of, and build
confidence in, the biomedical and behavioral health research that the
NIH conducts and supports across the nation and throughout the world.@
"Specifically, the PTI seeks to:

-   Increase the public=s understanding of how the NIH conducts and
    supports research;

-   Enhance public involvement in the NIH research related activities;

-   Enhance public access to, and understanding of, outcomes of
    research;

-   Increase public involvement and participation in clinical research;
    and

-   Strengthen interactions with the public regarding priority setting
    and stewardship of research for the public=s health."[^19]

Ironically, despite the heavy emphasis placed on translating scientific
knowledge to health care benefits in the Roadmap and on enhancing public
trust in the PTI, neither program contains specific research initiatives
designed to address how new discoveries will evolve from these enhanced
research settings into the development of new health policies and
practices, or to better understand the perspectives and concerns of the
general public. An NIH-wide ELSI research program, focused on ensuring
the safe and effective integration of new technologies into clinical
settings and on examining public attitudes towards research technologies
and information, would help to fill these gaps.

Just as ELSI research contributes to all levels of genomic research, it
also can contribute to all aspects of the NIH Roadmap. Within the first
theme, New Pathways to Discovery, ELSI work on intellectual property may
help maximize public and private benefit by allowing for a more
effective sharing of information among researchers and between the
research community and the pharmaceutical industry. For the second
theme, Research Teams for the Future, ELSI research not only can provide
data on the interactions among cross disciplinary research teams, but
also can provide a model for the value of inter- and multi-disciplinary
studies that span not only biological and clinical research, but also
include the social sciences, law and humanities. While other ICs
encourage the integration of biological and clinical studies, and some
social sciences studies, NHGRI=s ELSI Program is the only standing
program that regularly includes researchers from law and the humanities.
This research, which explores the impact of new biomedical discoveries
on the human condition, is crucial to understanding and addressing
issues involving the general public=s understanding and support for
research, one of the major goals of the third theme, Re-engineering the
Clinical Research Enterprise. Additionally, by supporting qualitative
and quantitative social sciences research into individual and societal
views of research and on the development and impact of regulations,
guidelines and policies, the ELSI Program can help to provide data that
can be used to harmonize research regulations and facilitate the
translation of basic research findings to clinical research settings and
ultimately to health care practice.

The online description of the Public Trust Initiative states that the
initiative rests on two "Basic Assumptions:

-   Gaining and enhancing public trust is a top priority for the NIH.

-   Enhancing public trust requires a long‑term commitment.@^18^

The ELSI Program, with its Congressionally mandated 5% set aside of the
HGP budget, was created as a long-term commitment by NIH to anticipate
and address both individual and societal concerns about advances in
genetic and genomic research. Most, if not all, of the ELSI studies
included within the Vision Document=s Grand Challenges are focused on
gaining a better understanding of the public=s attitudes toward and use
of new genetic and genomic information and technologies. For example, in
addition to the studies already highlighted, the ELSI Program has funded
an historical analysis of the concerns of Evangelical Christians about
genetic interventions,[^20] a study of the beliefs and attitudes of
individuals of Hispanic descent regarding hereditary prostate
cancer[^21] and a new qualitative study of the impact of prophylactic
mastectomy on the lives of women with BRCA mutations. While it is
difficult to quantify the impact of studies like these and the many
other similar studies funded by ELSI, the very existence of a federally
funded program that takes the concerns of the public seriously enough to
invest funds to explore and address these concerns can reasonably be
expected to increase public involvement in and trust for biomedical
research.

**Conclusions**

Since the completion of the first human sequence in April 2003, the ELSI
Program has revised its program announcements and funding priorities to
address the Grand Challenges identified in the Vision Document, and has
already funded a substantial body of research in many of these areas. It
has also released a targeted RFA on intellectual property issuesBone of
the areas identified in the Vision Document as needing immediate
attention. In addition, in response to persistent structural concerns
about the ELSI research enterprise, the Program has established a
Centers of Excellence in ELSI Research (CEERs) initiative that will
enable sustained multi-disciplinary research and training, and enable
the translation of ELSI research findings to products that can be used
by the research, health and social policy communities.

In short, the ELSI Program is well positioned to move forward into the
future of genetic and genomic research. Unfortunately, like much of the
biomedical research community, the ELSI Program is faced with a
shrinking budget just as it is launching a number of new initiatives. In
order for the ELSI Program to fully support these initiatives, it will
be essential to expand the base of support for ELSI research to include
all of NIH. The decision not to reissue the NIH-wide K01 and T15 ethics
announcements and the pending decision about the R01 announcement
coupled with the launching of the new Trans-NIH Roadmap and Public Trust
Initiatives create an opportunity to make the case to the rest of NIH
for this expansion, since ELSI research can provide much needed support
to both initiatives. For the Roadmap, ELSI research, through its
clinical and social sciences research studies, can help to facilitate
the translation of new discoveries from the bench to the bedside. With
the Public Trust Initiative, ELSI research can provide conceptual
clarity and a strong foundation of research data to help shape
successful interventions to improve the public=s confidence in
biomedical research.

**References**

[^1]: ?. Collins FS, Green ED, Guttmacher AE, Guyer MS. AA Vision for
    the Future of Genomics Research: A blueprint for the genomic era.@
    *Nature*. Vol. 422. 24 April 2003.

[^2]: . **GREEN, Robert C. \"Genetic Risk Assessment and Counseling for
    Alzheimers Disease\"**

    > Green RC, Cupples LA, Go R et.al. \"Risk of Dementia Among White
    > and African American Relatives of Patients With Alzheimer
    > Disease.\" *JAMA*. January 2002; 287(3): 329‑336.
    >
    > Cupples LA, Farrer LA, Sadovnick AD et al. AEstimating risk curves
    > for first-degree relatives of patients with Alzheimer=s disease:
    > The REVEAL study.@ (p.192-6) and Roberts JS, Barber M, Brown TM et
    > al. AWho seeks genetic susceptibility testing for Alzheimer=s
    > disease? Findings from a multisite,randomized clinical trial.@
    > (p.197-203) *Genetics IN Medicine*. July/August 2004; 6(4).

[^3]: . **ARMSTRONG, Katrina. Distrust, Race/ethnicity, and Predictive
    Genetic Testing.**

    > Peters N, Rose A, Armstrong K. AThe Association between Race and
    > Attitudes about Predictive Genetic Testing.@ *Cancer Epidemiology,
    > Biomarkers & Prevention.* March 2004;13(3):361-365.

[^4]: . **HENDERSON, Gail. Social Construction of Benefit in Gene
    Transfer Research.**

    > Henderson GE, Davis AM, King NMP et al. AUncertain Benefit:
    > Investigators\' Views and Communications in Early Phase Gene
    > Transfer Trials.@ *Molecular Therapy* 2004.

[^5]: . **Genetic Variation Consortium Publications**. More than 30
    individually authored peer reviewed publications or books have
    resulted from these two RFAs and one jointly authored publication. A
    selection of these publications follows.

    > Sankar P, Cho MK, Condit CM, Hunt LM, Koenig B, Marshall P, Lee
    > SS, Spicer P. AGenetic Research and Health Disparities@ *JAMA*.
    > 2004;291:2985‑2989
    >
    > Elliott C, Brodwin P. \"Identity and genetic ancestry tracing.\"
    > *BMJ* December 2002; 21‑28(325): 1469‑71.
    >
    > Foster MW, Sharp RR. \"Beyond race: towards a whole-genome
    > perspective on human populations and genetic variation\" *Nature
    > Reviews Genetics*. October 2004;Vol. 5:790-796
    >
    > Lee SS. \"Race, Distributive Justice and the Promise of
    > Pharmacogenomics: Ethical Considerations,\" *Amer. Jour. of
    > PharmacoGenomics. 2003;* 3(6): 385-392.
    >
    > Rothstein MA (ed.) *Pharmacogenomics: Social, Ethical, and
    > Clinical Dimensions*. Wiley‑Liss; (January 2003) 368p.
    >
    > Sankar P, Cho MK. \"Toward a new vocabulary of human genetic
    > variation.\" *Science.* November 2002; 298(15): 1337‑1338.

[^6]: 6\. **CONDIT, Celeste M. \"Race and Public Communication About
    Human Variation\"** This grant has produced 6 publications to date,
    including:

    > Condit C. \"What is \'public opinion\' about genetics.\" Nat Rev
    > Genet October 2001; 2(10): 811-815.
    >
    > Condit CM, Parrott R, Harris TM \"Lay understandings of the
    > relationship between race and genetics: Development of a
    > collectivized knowledge through shared discourse.\" Public Underst
    > Sci. 11(4): 373-387 October 2002.
    >
    > Condit C, Templeton A, Bates B, Bevan JL, Harris TM \"Attitudinal
    > barriers to delivery of race‑targeted pharmacogenomics among
    > informed lay persons.\" (385‑392) and Bevan JL, Lynch JA, Dubriwny
    > TN et al. \"Informed lay preferences for delivery of racially
    > varied pharmacogenomics.\" *Genetics in Medicine*.
    > September/October 2003; 5(5): 393‑399.

[^7]: . **PARENS, Erik. \"Tools for Public Conversation about Behavioral
    Genetics\"**

    > Parens E. \"Genetic Differences and Human Identities: On Why
    > Talking about Behavioral Genetics Is Important and Difficult.\"
    > *Hastings Center Report*. Special Supplement. January‑February
    > 2004: S1‑S34.

[^8]: . **SINGER, Eleanor. Beliefs about Genes & Environment as Causes
    of Behavior.**

    > Singer E. et al. ARacial and Ethnic Variations in Knowledge and
    > Attitudes about Genetic Testing,@ *Genetic Test.* 2004 Spring;
    > 8(1): 31-43.

[^9]: . **JUENGST, Eric T. \"Anticipating Enhancement: Ethical, Legal
    and Social Issues\"** This grant and its two competitive
    continuations have produced 14 publications to date. A brief
    selection follows.

    > Juengst ET. \"Can Prevention be Distinguished from Enhancement in
    > Genetic Medicine?\" *Journal of Medicine and Philosophy*. 1997;
    > 22: 125‑142.
    >
    > Mehlman MJ. \"How Will We Regulate Genetic Enhancement?\" *Wake
    > Forest Law Review*. Fall 1999; 34(3): 671‑714.
    >
    > Juengst ET, Binstock RH, Mehlman MJ et al. \"Aging ‑ Antiaging
    > research and the need for public dialogue.\" *Science*, 299(5611):
    > 1323‑1323 February 28, 2003.

[^10]: . **SAGOFF, Mark. Concepts of Nature, Biotechnology, and the
    Human Genome.** This grant has produced 10 publications to date. A
    selection of these publications follows.

    > Sagoff M. AIntellectual Property and Products of Nature,@
    > *American Journal of Bioethics*. 2002; 2(3): 12-13.
    >
    > Wasserman D. ASpecies and Races, Chimeras and Multiracial People.@
    > *American Journal of Bioethics*. 2003; 3(3).
    >
    > Wasserman D. AThis Old House: The Human Genome and Human Body as
    > Objects of Historic Preservation.@ *Politics and the Life
    > Sciences*. March 2003; 22(1); 43-47.

[^11]: . Hanna KE. AThe Ethical, Legal, and Social Implications Program
    of the National Center for Human Genome Research: A Missed
    Opportunity?@ in *Society=s Choices: Social and Ethical Decision
    Making in Biomedicine*. RE Bulger, EM Bobby and HV Fineberg eds.
    Washington DC, National Academy Press, 1995. P.432-457.

[^12]: . Juengst ET (1996) Self-Critical Federal Science? The Ethics
    Experiment within the U.S. Human Genome Project. *Social Philosophy
    & Policy* 13(2): 63-95.

[^13]: . Spence A and M Rothstein. \"Report Of The Joint NIH/DOE
    Committee To Evaluate the Ethical, Legal, and Social Implications
    Program of the Human Genome Project.\" December 1996.

[^14]: . ELSI Research Planning and Evaluation Group (2000) *A Review
    and Analysis of the Ethical, Legal, and Social Implications (ELSI)
    Research Programs at the National Institutes of Health and the
    Department of Energy.* NIH Publication No. 00-4867.

[^15]: 15\. ELSI Research Advisors and ELSI Policy and Planning Group.
    *The Role of ELSI Research and Policy Activities in the NHGRI Plan.
    [http://www.genome.gov/page.cfm?pageID=10005516]{.underline}*

[^16]: ^?^A notable product of one of these translational activities is
    the series of articles published in JAMA in 1997 by the Cancer
    Genetic Studies Consortium laying out recommendations for informed
    consent and follow-up care of individuals with genetic
    predispositions to breast, ovarian and colon cancers. To date, these
    publications have been cited more than 750 times in the scientific
    literature.

[^17]: 16\. U.S. House of Representatives Committee on Government
    Operations. "Designing Information Policy: The Need for an
    Independent Policy Review of the Ethical Legal, and Social
    Implications of the Human Genome Project." House Report 102-478,
    April 2, 1992, p.4.

[^18]: . NIH Roadmap Overview.
    [http://nihroadmap.nih.gov/overview.asp]{.underline}

[^19]: . NIH Public Trust Initiative Mission Statement.
    [http://publictrust.nih.gov/mission.cfm]{.underline}

[^20]: . **DAVIS, John J. AConcerns of Evangelicals about Genetic
    Interventions\"**

    > Davis JJ \"Ethical Concerns of American Evangelicals Relative to
    > Genetic Interventions.\" *Ethics and Medicine* (Accepted for
    > publication).

[^21]: . **ARAR, Nedal H. \"Cultural and Ethical Issues in Genetic
    Family Studies\"**

    > Arar NH, Plaetke R, Arar MY. et al. \"Incorporating the Contextual
    > Assessment Approach to regimens used in genetic family studies.\"
    > *Genetics in Medicine*. November/December 2002: 4(6): 451‑463.
    >
    > Arar NH, Hazuda HP, Plaetke R. et al. \"Familial Clustering of
    > Diabetic Nephropathy: Perceptions and Risk Recognition Among
    > Mexican‑American Patients With a Family History of Diabetes.\"
    > *Diabetes Spectrum*. 2003: 16(3): 136‑142.