7440. 
Federal Register / VoL 55, No. 41 / Thursday, March 1, ISSO / Notic^ 
Sohcommittp* (IS people), includes sdentiets, 
physidans, lawyers, ethicists. and ae'veral 
laypeople. 
The NIU Guidelines tor BatnuahinanlDNA 
.V Molecules require, thstnodcenf tnpptfng* q| 
the NIKRexujmbinant DKiLAdvisary 
Cooimitlee (RAC) be published in the Federal 
Register at least 30 days pnnr to the meeting 
Federalrcgulations requtfe.alleastliS.deya . 
advance notice ofallatlier meetings through, 
the Federal Register pobllcatroa (e-g.. 
subcommittee meetings). All meetings ace to 
be open to the press and the public, unless 
closed in accordance with 5 DSC 5S2b. 
The NIH has authority only over certain 
federally funded research. However, many 
privare companies that do not receive federal 
support voluntarily aubmit proposals to NIH 
for review. Ih additibn, the Foodand Drug 
Administration (TOA), which has iurisdiction 
over (frug-and biofogfcal products intended 
for osE- in human patients', must also review 
and approve experiments involving gene 
therapy for human patients, whether thp 
research is federally funded or not 
Since thetSTUs, general interest in human 
gene therapy has increased both here and 
abmadh dong with awareness of the. need for 
oversi^t and teguhitfun. In this country, in 
1974. the Secretary. DeparOnent of Health, 
Education, and Welfare (now the DHHS), 
chartered the Recombinant DMA Advisory 
Committee (RAC) to. develop- 
recommendatioia foe the cegulatiooof 
recombinanl DMA seaeaccln. The Guidelines, 
foe Research Involving Recombinant DNA 
Molecules were published in 19r6,In-.1978, 
the Guidelines were revised, relaxing many 
of the requirements forrecombinaotDNA 
expeciments. 
In. 1980, at the urging o£ the three major 
religious groups in. this country, the Prudent 
requested that rt>P-Pr p<ifipnt *m. f!nfnmi]t <if»ti. 
for the Stuffy Pi- nhlpma- in 
and Biomedical and Behavioral Research, 
-examrnethe topjc-ofhuman. genetic ■ 
pnginppriTig In Hoveicber 1982, One o£ the 
Commissioiz's eleven reporta. Splicing t 
-The Soczai and Ethical.liaaues of Genetic ... . 
-'Engineering wiOlBuinaQ.'Beings.'was 
submitted to the President and Confess. A 
subcommittee of the United States House of 
Representativas held three days of hearings 
on the report, Cnngr «»««->iriat- interest alao 
resulted in e 1984 baekgioaod paper entitled^ 
Human Gene Therapy, produced by the 
Office of Technology Aaaes«aieat.Ia 
response to one recommendatioa of the 
President’s Commissioc, the NIH 
Recombinant DNA Advisory Committee 
fonned a working groop. in. 1584, to specialize 
in human gene therapy. This is now the 
Huma n Gene Therapy .‘tiiyvTomimttjp In. iggg. 
the White House Office of Science and 
Technology Policy created the Biotechnobgy 
Science Coordinating Committee (BSCC). The 
Committee includes federal oEEciels 
representing the Nadonal Institutes of Health, 
the Envirocmeelal. Protection Agency, the 
U.S- Department of Agnculture. the Foodand 
Drug Administration, and the Nadonal 
Science Foundation. The 6SCC provides • - 
-forum for discussion of biotechxiology issues . 
and an opportunity to make 
recommendations on the federal rogslation of 
hictechnoloQ'. 
Legislative inCerest continues to be 
expressed through activities of tbe- 
Subcomisittee on Science. Research and 
Technology of the House Committee on. 
Science and Technology and theOflice of 
Technology Asaesament. In 1986, a 
Congressional. Biomadical Ethics Board was 
formed to oversee, research, and 
developmentsingenetic engineenng. This 
Board is composed of six Senators and six 
Representatives, 
International interest ns huinaa gene 
therapy has resulted in a number ^ reports 
and recommendations submitted by foreign 
government committees. Foe exam^e, in 
1987, the Parliamentary Assembly of the 
Council of Europe issued a statement 
including proposals, for oversight and 
recommendations for certain restrictibna on 
human genetic engineering. (Other reports 
and statements are. listed at the and of tiiia 
brochnre under Suggestions for Further 
Study4 
In summary, research, on human gene 
therapy is being monitored at both the Local 
and national levels, here and abroad. 
Members of the general public are 
represented and are encouraged to. 
participate in the public dbeussinn of this 
new area of biomedical research.. . 
PART 3— NIH ■PfMNTSTQ CONSIDER’ FOR 
GENEIHERAPY RESEARCHERS 
In anticipation of the&strequesf to 
perform a human gene therapy exper im e n t 
the Human Gene T h er a py Subcommittee- 
prepared a document c^ed Points to 
Consider m the Design and Sabmisaron' of 
Protocols for the Transfer oTRecomhinant 
-DNA into the Genome of Human Subjects. 
’This dacumenf was approvedby the NIH 
Reesmbinanf DNA Advraery GbmimCtee and 
the Dfrector eftha NIH in 1S88. ThePbuits- to 
Consider document prsviifes guidance to 
physidana and sdentistawhoan ptannihg to 
submit proposals to the NIH forgene therapy 
* treatment of patients. It dasodies' the 
conaideratwins that have been kfenCified in 
the studies and hearings mentioned 
ptevionafy- as the most i mp o r t an t nr ^ 
evalnating this new- mode of treatment. 
In the Points tn Consider, researchers are 
asked: 
What diseased? you intend to- treat with 
gene tfaerapyt 
Why dn you consider this disease tnbean 
appropriate candidate: for traatnent with, this 
new method? 
Ea answering these questions, the 
researdier wul dbeuss the setiiouancss of the 
disease, any altereative therapiesvand- the 
possible advantages of gene therapy for at 
least some patients. 
Another part of the ’Points to Consider’ 
asks: 
What laboratory studies have be en done, 
with cells and live animals, that make 
researchers hopeful that gene therapy will 
help patients rather than harming them? 
Kcue the researcher will provide the results 
of studies peiformed in hisjher laboratory or 
in other iaboratscies around the world. 
Especially important wQl be studies 
’ demonstrating that gene therapy does not 
harm labocatocy animals and in fact 
demonstrates that the desired biological 
effects occor. 
Even if the precediag questions ate 
satisfactorily ansMrered. important questions 
about the proposed use of genetherapy in 
patients will remain. ’Ehe ’Taintrto 
Consider” aslc the hdinwmgfmzr questions: 
What are the probahle benehts and harms 
of the propcsed rieatment, both to the patient 
and to otfares? 
' If there are several patients who need gene 
therapy bur only one of (hem can be treated 
initially, how- wiU. selection be made in * way 
that treats all patients fan-fy? 
How will patients— or. in the case of ysung 
children, the parents of patients — ba- properfy 
biformed about the possibfe benefits and 
risks of gene therapj'? 
What steps will be taken to protect the 
privacy of the patient and the patient’s 
family, while at the same time m fucmlug the 
public- about the results of gene tf ieiapy?. ' hr 
the bitrodnction to the “Points to Consider:"' 
reference is made to two possible 
undesirable or unintentional consequences of 
somatic cell gene therapy. TransmisrioRof 
altered genes to a patient's oBspring, and 
viral infection of persons who come m 
contact with the patient The Sobcommiltee 
requesb that rese uce &e tai de sen be what 
actions, will be taken to prevent either event 
from on:.ii r ling, 
The- Points to- Consider acknowledge» the 
public concerts aboot soma aspects- oC buoiaa 
gene thsrapy,h isadscTstecDgintinn.of the- 
social concenr that surrounds: the general 
discussion of human gene therapy, the 
(Subcommillee) will conChue to consider the 
possible long-range effects of applying 
knowledge gained from these and related 
experimenb.' For the moment, the 
Subcommittee' agrees with the concTusioirih 
the Office of Technology Asses smeat 'r report 
Human Gene Therapy that: 
Gvic, religious, sdentiffc, and medical 
groups have all accepted, in prindpte;, the 
appropriateness of gene therapy of somatic 
cells in humans for speciBc genetic dUeases. 
Somstic cell gene therapy is seeir as an 
extension of present methods of theraiiy that 
might be pre fe rable to other tedmologies: 
• While the RAC and its Subcotrunittee 
believe that gene therapy fer non- 
tepraductive, or somatic, cells holds promise 
for patients suffering from certain genetic and 
other diseases, they will seek to ensure (list 
patients are not subjected to unreasonable 
risk of harm, excessive discomfort or 
unwanted invasion of privacy and that they 
will receive special cate, monitoring, and 
consideration. The pubDc will be informed 
about every' step that is taken with this new 
teefaruque. 
PART 4— SUGGESTIONS FOR FURTHER 
STUDY 
There ace several helpful books, articles, 
mA m videotape on- the subject of gene 
therapy. The following is a selection, of 
materials oriented toward the- lay reader. 
-READING MATERIAL 
UE. National Institute* of Health. 
Recomhinanl DNA Advsioty Committee. 
Point* to Consider in the Design- and 
Submission of Protocola for the Transfer of 
fi^/-QfTi Vii nnn f DNA into the Genome of 
Human Subjects. Available fronv the Offices 
[42] 
Recombinant DNA Research, Volume 14 
