GAO-01-65R Fetal Tissue Research

United States General Accounting Office

Washington, DC 20548

October 4, 2000

The Honorable Arlen Specter

Chairman

The Honorable Tom Harkin

Ranking Minority Member

Subcommittee on Labor, Health and Human

Services, and Education

Committee on Appropriations

United States Senate

The Honorable Bob Smith

United States Senate

Subject: Human Fetal Tissue: Acquisition for Federally Funded Biomedical Research

Human fetal tissue is used in basic and preclinical biomedical research to advance

knowledge of basic biological processes and improve research involving potential

therapeutic approaches. It is also used in therapeutic transplantation or clinical

research that involves the transplantation of human fetal tissue into patients for the

cure or amelioration of diseases and disorders. The study, analysis, or use of human

fetal tissue in biomedical research is considered by many medical researchers to

offer promise for treatment of disorders and diseases such as Parkinson’s disease,

Alzheimer’s disease, and diabetes.

You requested that we study the involvement of federal agencies under the

jurisdiction of the Senate Committee on Appropriations, Subcommittee on Labor,

Health and Human Services, and Education in the acquisition of human fetal tissue

for biomedical research. You specifically asked us to provide information on (1)

which federal agencies under the Subcommittee’s jurisdiction sponsor biomedical

research using human fetal tissue, (2) the number of human fetal tissue samples

acquired annually, (3) the number of central human fetal tissue supply organizations

receiving federal funds, (4) the costs associated with acquiring human fetal tissue, (5)

how researchers select and monitor human fetal tissue suppliers, (6) the extent to

which federal human fetal tissue acquisition policies adhere to federal law, and (7)

how federal agencies ensure that federally funded researchers comply with human

fetal tissue law.

To address these questions, we interviewed officials from the Department of Health

and Human Services (HHS) and the National Institutes of Health (NIH), organizations

that supply human fetal tissue for research, and selected institutional review boards

that are responsible for the oversight of specific federally funded biomedical research
2 GAO-01-65R Fetal Tissue Research

grants involving human fetal tissue. To gather information about the amount,

sources, and costs of human fetal tissue used in biomedical research, we conducted a

survey of NIH funded principal investigators for extramural and intramural research

using human fetal tissue in fiscal years 1997, 1998, and 1999. Finally, we reviewed the

laws, regulations, and policies relevant to human fetal tissue. We restricted our

analysis to research projects that directly received human fetal tissue.1We carried out

our work between July and September 2000 in accordance with generally accepted

government auditing standards.

In brief, HHS officials reported that NIH is the only federal agency under the Labor,

HHS, and Education Subcommittee’s jurisdiction that sponsors research using human

fetal tissue. On the basis of information supplied to us by NIH, we estimate that NIH

awarded approximately $17.0 million for 103 research grants using human fetal tissue

in fiscal year 1999. Principal investigators who responded to our survey acquired

12,116 human fetal tissue samples in fiscal years 1997 through 1999 for use in NIHsponsored research. NIH funded three central human fetal tissue suppliers to provide

human fetal tissue to biomedical researchers in fiscal year 1999. The costs of

acquiring human fetal tissue were generally low. In fiscal year 1999, 49 percent of the

principal investigators in our survey received human fetal tissue without paying an

acquisition fee. Among those who did pay an acquisition fee, the average fee per

sample was $80 in fiscal year 1999. The median number of tissue samples received by

principal investigators in fiscal year 1999 was 26. In fiscal year 1999, 62 percent of

principal investigators received human fetal tissue from central fetal tissue supply

organizations, 31 percent from academic medical center hospitals, and 30 percent

from health clinics or physicians’ offices.2 The principal investigators identified

quality of the tissue supplier and a supplier’s compliance with relevant regulations as

the primary criteria for selecting their human fetal tissue suppliers. We found that

federal human fetal tissue procurement policies and guidance are consistent with

federal law. Review boards that are established at each institution performing HHSfunded biomedical research have the primary responsibility for ensuring that the

procedures for acquiring human fetal tissue comply with federal, state, and local

laws. The Office for Human Research Protections (OHRP) is the HHS entity that

oversees the ongoing review practices of these institutional review boards.

1

This definition excludes (1) research involving human cord blood, placenta, amniotic fluid, and

chorionic villi; (2) research involving derivatives of human fetal tissue such as human fetal cell

cultures or human fetal cell lines; (3) studies involving a collection of existing human fetal tissue; and

(4) pathology studies or autopsies.

2

Sum of percentages is greater than 100 because some principal investigators had more than one

supplier.
3 GAO-01-65R Fetal Tissue Research

BACKGROUND AND METHODOLOGY

The NIH Revitalization Act of 1993 (P.L. 103-43) added two provisions to the Public

Health Service Act regarding the acquisition and use of human fetal tissue.3 The NIH

Revitalization Act4prohibits a person from knowingly acquiring or transferring

human fetal tissue for valuable consideration if the transfer affects interstate

commerce. The statute defines “valuable consideration” as excluding reasonable

payments associated with the transportation, implantation, processing, preservation,

quality control, or storage of human fetal tissue. For therapeutic transplantation

research, the NIH Revitalization Act requires written statements by the donor, the

physician who obtained the tissue, and the researcher receiving the tissue to ensure

that the provisions of the law are met. It further requires that all applicable state and

local laws must be followed.5

Because we found no central source of information about the amount of human fetal

tissue used for research or the number of human fetal tissue suppliers, we conducted

a survey of principal investigators for all NIH-funded extramural and intramural

research NIH reported to us as possibly using human fetal tissue for fiscal years 1997,

1998, and 1999. In the survey, we asked the principal investigators to identify (1) the

number and type of entities they selected to be human fetal tissue suppliers, (2) the

amount of tissue they received, (3) the number of shipments or acquisitions they

received, and (4) the direct and indirect costs associated with human fetal tissue

acquisition. We also asked principal investigators to identify the relevant oversight

bodies at their institution, to describe the policies that exist at their institution

regarding research using human fetal tissue, and to explain how their institution

ensures compliance with federal, state, and local laws. We sent the survey

instrument to all 160 of the investigators identified for us by NIH as having a research

grant that may have involved the use of human fetal tissue for fiscal years 1997, 1998,

and 1999. The survey was returned by 151 of the principal investigators, for a

response rate of 94 percent. Of those respondents, 93 acquired fetal tissue for their

research and completed the entire survey form, 47 told us that their research did not

use human fetal tissue or that they did not acquire human fetal tissue in fiscal years

1997, 1998, and 1999, and 11 told us that they did not directly acquire human fetal

tissue but used tissue acquired by another researcher included in our survey.6

3

Prior to the enactment of the NIH Revitalization Act, the National Organ and Transplantation Act of

1988 (P.L. 100-607) expanded the definition of “human organ” in the Public Health Service Act (42

U.S.C. section 274e) to include human fetal organs and tissue. This act thus prohibits the transfer of

human organs, including human fetal tissue, for valuable consideration for use in human therapeutic

transplantation.

4

Section 112 of the NIH Revitalization Act, adding section 498B of the Public Health Service Act (42

U.S.C. section 289g-1).

5

For a fuller description of this provision, see section 111 of the NIH Revitalization Act, adding section

498A of the Public Health Service Act, 42 U.S.C. section 298g-1.

6

One hundred nineteen of the principal investigators received NIH grants in fiscal year 1999 (the

remainder received funds only in fiscal years 1997 or 1998). For those with fiscal year 1999 grants the

response rate was 97 percent; 68 acquired human fetal tissue in fiscal year 1999, 39 reported that they
4 GAO-01-65R Fetal Tissue Research

FEDERALLY FUNDED BIOMEDICAL

RESEARCH USING HUMAN FETAL TISSUE

HHS officials told us that NIH is the only federal agency under the Labor, HHS, and

Education Appropriations bill that sponsors biomedical research using human fetal

tissue. Separately, the Centers for Disease Control and Prevention told us that it does

not conduct research using human fetal tissue. On the basis of information supplied

to us by NIH, we estimate that NIH awarded to our survey respondents

approximately $17.0 million for 103 research projects that used human fetal tissue in

fiscal year 1999.7The researchers who responded to our survey collectively received

$12.3 million in funding for extramural research at universities and research

institutions, $3.2 million in funding for NIH intramural research, and $1.5 million for

central human fetal tissue supply organizations.

NUMBER AND SOURCES OF TISSUE SAMPLES ACQUIRED

The NIH-sponsored biomedical researchers who responded to our survey acquired an

average of roughly 4,000 samples of human fetal tissue in each year from fiscal years

1997 to 1999 (see table 1). We defined a tissue sample as a separate amount of tissue,

or a single piece of tissue, in one vial. In fiscal year 1999, researchers received 4,147

samples in 1,878 shipments or acquisitions. The median number of tissue samples

received by principal investigators in fiscal year 1999 was 26.

Table 1: Human Fetal Tissue Samples Acquired, by Fiscal Year

Fiscal year Number of fetal tissue samples

1997 3,676

1998 4,293

1999 4,147

Total 12,116

The principal investigators we surveyed received human fetal tissue most often from

central tissue suppliers. Among principal investigators who identified their sources

for human fetal tissue in fiscal year 1999, 62 percent received human fetal tissue from

central tissue suppliers, 31 percent from academic medical center hospitals, and 30

did not use human fetal tissue in their research or that they did not receive human fetal tissue in fiscal

year 1999, and 9 reported that they did not directly acquire human fetal tissue but used tissue acquired

by another researcher we surveyed. In addition to data from the 68 researchers who acquired tissue in

fiscal year 1999, our analyses for that year also included data from 10 researchers with NIH grants for

only fiscal years 1997 and/or 1998 who told us that they also acquired human fetal tissue in fiscal year

1999.

7

This total was calculated by summing the grant funding amounts we received from NIH for survey

respondents who told us that their research used human fetal tissue in fiscal year 1999. This total

probably is slightly understated, however, because some of the researchers who did not respond to our

survey may have used human fetal tissue.
5 GAO-01-65R Fetal Tissue Research

percent from health clinics.8

Fifty four percent of all of the human fetal tissue

samples received by the NIH-sponsored researchers we surveyed came from central

tissue suppliers in fiscal year 1999. Likewise, 34 percent of the tissue samples came

from health clinics and 10 percent from academic medical centers.

CENTRAL TISSUE SUPPLY ORGANIZATIONS

NIH sponsors three central human fetal tissue supply organizations. The Birth

Defects Laboratory at the University of Washington is funded by NIH for the sole

purpose of providing human fetal tissue to federally funded biomedical researchers.

While most of the laboratory’s funds are provided by NIH, it also charges researchers

a small fee for the human fetal tissue samples it collects, prepares, and distributes.

The laboratory distributed 2,869 human fetal tissue samples and collected $52,035 in

fees directly from researchers in fiscal year 1999. NIH provided a grant award of

$346,743 to maintain the laboratory’s capabilities in fiscal year 1999. NIH also funds

the Brain and Tissue Banks for Developmental Disorders at the University of

Maryland and the University of Miami School of Medicine/Children’s Hospital of

Orange County primarily to serve as suppliers of human nonfetal tissue for the study

of developmental disorders, but both banks also supply a relatively small amount of

human fetal tissue to biomedical researchers. In fiscal year 1999, NIH funds totaled

$563,823 for the University of Maryland Bank and $574,643 for the University of

Miami Bank. The University of Maryland Bank provided 195 human fetal tissue

samples to investigators in fiscal year 1999, and the University of Miami Bank

provided approximately 40 samples between March 1 and August 31, 1999.

In addition, some researchers obtained human fetal tissue from private, nonprofit

central tissue supply organizations that did not directly receive federal funds. In their

responses to our survey, the principal investigators who received tissue from these

sources most frequently obtained tissue from Advanced Bioscience Resources,

Incorporated (Alameda, California), and the Albert Einstein College of Medicine

Human Fetal Tissue Repository (New York, New York).

COSTS OF ACQUIRING HUMAN FETAL TISSUE

The direct acquisition fees for human fetal tissue were low. In fiscal year 1999, 49

percent of the respondents to our survey did not pay any acquisition fees for the

human fetal tissue they received. Among those who paid acquisition fees in fiscal

year 1999, investigators reported an average fee of $80 per human fetal tissue sample,

with a minimum fee of $2 and a maximum fee of $214. In addition, tissue acquisition

fees varied substantially among the different sources identified in our survey. Only

one of the researchers who received human fetal tissue from academic medical

centers paid an acquisition fee ($12). More than four-fifths of the researchers who

received tissue from health clinics paid no fee. The fees per sample of human fetal

tissue from health clinics ranged from $2 to $75, with an average of $22. In contrast,

8

Sum of percentages is greater than 100 because some principal investigators had more than one

supplier. Three percent of these respondents did not categorize their tissue source.
6 GAO-01-65R Fetal Tissue Research

78 percent of the researchers receiving human fetal tissue from a central tissue

supplier paid an acquisition fee–-those fees ranged from $5 to $214 per sample, with

investigators paying an average fee of $96.9

Second, some of the principal investigators who completed our survey had additional

expenses for transporting, processing, preserving, storing, and ensuring the quality of

human fetal tissue specimens, even if they paid nothing to acquire the tissue. For all

of the principal investigators who responded to our survey, total expenditures for

acquiring human fetal tissue in fiscal year 1999 totaled approximately $359,000,

including both tissue acquisition fees and these other expenses (see table 2). This

total includes about $142,000 in acquisition fees, $80,000 in shipping and

transportation costs, and $135,000 in other internal laboratory costs for processing,

preserving, storing, and ensuring quality.10

Table 2: Total Costs Related to Acquiring Human Fetal Tissue, Fiscal Year 1999

Cost category Number of

investigators

incurring cost

Average annual

cost per

investigator

Total for all

investigators

Acquisition fee 40 (51%) $3,554 $142,144

Shipping and

transportation

costs

42 (54%) $1,914 $80,405

Other direct costs 9 (11%)a $176 $1,580

Internal costs 13 (17%)b$10,350 $134,550

Total $358,679

a

Two respondents who said that they had other direct costs but did not provide a cost figure are not

included.

b

Seven respondents who said that they had internal costs but did not provide a cost figure are not

included.

CRITERIA FOR SELECTING HUMAN FETAL TISSUE SUPPLIERS

In response to an open-ended question on our survey, principal investigators reported

that quality of tissue and compliance with federal regulations were their primary

criteria for choosing a human fetal tissue supplier. Overall, 55 percent of the

respondents who received human fetal tissue in fiscal year 1999 told us that they

9

Twelve percent of researchers who obtained human fetal tissue from central supply organizations

paid no fee. Ten percent of researchers who identified central supply organizations as the entity that

supplied their tissue did not tell us whether or not they paid an acquisition fee.

10Shipping and transportation costs include any costs associated with transporting tissue samples from

the supplier to the researcher by any means, including by personal delivery or commercial shipping

company, and shipping supplies such as sample containers or sterile media provided by the

researcher. Other direct costs include renting space at a supplier’s facility, in-kind services or

donations of staff time or supplies to the tissue supplier, and any other financial considerations to the

tissue supplier. Internal costs are any costs researchers may have incurred as a result of acquiring

fetal tissue that they would not have otherwise, such as equipment for storing the tissue.
7 GAO-01-65R Fetal Tissue Research

selected a tissue supplier on the basis of the qualifications and reliability of its staff,

its reputation for high-quality work, or other reasons indicating a preference for a

high-quality supplier. Forty-four percent of these 1999 respondents told us that the

supplier’s compliance with federal and state laws, or its nonprofit status, was an

important reason for their selection. Thirty-seven percent told us that the location of

the tissue supplier was important (21 percent told us that the tissue supplier was part

of their institution). Fewer respondents (29 percent) selected a tissue supplier simply

because appropriate human fetal tissue was available there. Finally, 9 percent of

those who received human fetal tissue in fiscal year 1999 told us that the low cost of

the tissue was a factor in their selection of a supplier.

HUMAN FETAL TISSUE POLICIES AND GUIDANCE

The NIH Revitalization Act of 1993 places limits on the procurement of human fetal

tissue. The statute bars anyone from knowingly acquiring, receiving, or transferring

human fetal tissue for valuable consideration if the transfer affects interstate

commerce. For therapeutic transplantation research, it further bars directed

donations of human fetal tissue and payment of valuable consideration for costs

associated with terminating a pregnancy. Each of these prohibitions carries criminal

penalties, including fines and imprisonment. Because these provisions do not require

implementing regulations,11 NIH addresses the importance it attaches to these

statutory requirements and the criminal penalties that the prohibitions carry through

guidance to its grantee researchers. In its forthcoming policy statement on “Research

on Human Fetal Tissue,” NIH emphasizes that “the scientific and ethical challenges

associated with research utilizing human fetal tissues make it imperative that

researchers and their institutions be clearly aware of and in compliance with federal

requirements,” especially those that carry criminal penalties.

INSTITUTIONAL REVIEW BOARDS

Except for research conducted at its own facilities, NIH does not directly oversee the

conduct of research using human fetal tissue. Instead, under the regulations

regarding the protection of human subjects, institutional review boards oversee HHSfunded research using human fetal tissue.12 These review boards are required at all

institutions conducting HHS-supported research. The boards are responsible for

approving research proposals before studies begin and for periodically reviewing

studies after they are under way to ensure compliance with relevant regulations for

the protection of human subjects. OHRP is the HHS entity responsible for ensuring

that the institutional review boards are conducting the appropriate reviews of HHSfunded research using human fetal tissue. Before grant funds are distributed, the

grantee institution submits an “assurance” to OHRP. The assurance is a written

11In addition, although not directly addressing the procurement of human fetal tissue, NIH regulations

specifically require that “activities” involving these materials must be in accordance with any

applicable state or local laws (45 C.F.R. section 46.210).

12Almost all of our survey respondents identified the institutional review board at their institution as

the body responsible for oversight of their research.
8 GAO-01-65R Fetal Tissue Research

statement of an institution’s requirements for its institutional review board and

human-subject protections. If the institution receives only one grant from HHS, a

single project assurance is submitted to OHRP. If the institution receives many HHS

grants, a multiple project assurance is submitted. In the assurance, the institution

states that the research will be conducted in compliance with applicable federal,

state, and local laws. Institutions are required to renew multiple project assurances

every 5 years after an initial period of 3 years. Continuing reviews of the HHS-funded

projects are conducted annually by the institutional review boards.13

NIH’s Office of Intramural Research periodically reviews each intramural investigator

using fetal tissue to confirm that they are complying with the relevant requirements.

AGENCY COMMENTS

NIH and OHRP officials reviewed a draft this report. They provided technical

comments, which we incorporated where appropriate.

-----

We will make copies of this letter available to those who are interested on request.

Major contributors to this report were Martin T. Gahart, Emily J. Rowe, Jenny C.

Chen, Lisanne Bradley, and Stefanie Weldon. Please contact me at (202) 512-7119 if

you have any questions.

Janet Heinrich

Director, Health Care - Public Health Issues

(201089)

13Our review did not evaluate the effectiveness of institutional review board oversight. We previously

reported that NIH-sponsored investigators conducting therapeutic human fetal tissue transplantation

research were in compliance with federal laws and regulations. See NIH-Funded Research:

Therapeutic Human Fetal Tissue Transplantation Projects Meet Federal Requirements (GAO/HEHS-97-

61, Mar. 10, 1997).