Federal Register / Vol. 55, No. 41 / Thxirsday, March 1. 1990 / Notices 
7439 
The possible new treatment is called 
human gene therapy and is one of a series of 
‘:emerging genetic techniques, commonly 
called genetic engineering, based on new 
knowledge about how genes work. 
It is expected that researchers will soon 
request approval for a human gene therapy 
experiment. Many benefits are foreseen. 
However, because of the novelty of the field, 
concerns about the discriminatory and 
eugenic misuse of the techniques, and the 
possible effects on future generations from 
some types of human gene therapy, important 
ethical questions will also be raised. 
This brochure is intended to provide basic 
information for the general public about the 
new technique and its significance. It was 
written at the request of the public 
representative of the Human Gene Therapy 
Subcommittee. Contributors to the writing 
and revision of this document are listed in 
part S. 
Anne Reed Witherby, Public Representative 
CONTENTS 
PART 1— DISEASES AND THEIR 
TREATMENT 
A description, in lay language, of the 
medical facts about candidate diseases, 
current treatments, and the new possibility of 
treating certain diseases with human somatic 
(non-reproductive] cell gene therapy. 
PART 2— GOVERNMENTAL OVERSIGHT 
AND PUBUC PARTICIPATION 
Information about local and national 
oversight public involvement and a brief 
background of the growing interest in the 
subject here and abroad. 
PART 2-NIH TOINTS TO CONSIDER- FOR 
GENETHERAPY 
Researchers 
- - A summary of the pertinent sections in the 
Points to Consider document written by the 
Human Gene Therapy Subcommittee as a 
' guide for researchers seeking approval for 
'tuman-gene'tiierapy experiments. ^ 
PART 4 — SUGGESTIONS FOR FURTHER 
STUDY 
A list of some U.S. Government 
Publications, recent statements by religious 
organizations, European Government 
Reports, and a few books and articles, and a 
videotape. 
PART 5— LIST OF CONTRIBUTORS 
PART 1— DISEASES AND THEIR 
TREATMENT 
The human body is made up of about fifty 
trillion cells. Inside each cell is information 
that tells the cell what to do and how to 
work. This information is contained in genes, 
which are made up of a chemical called DNA. 
Through small differences in the structure of 
the DNA, the information is coded and 
stored, just as different letters combine to ' 
form words which are then stored in books. 
All the many activities that a cell does start 
with reading part of the information that is 
‘ Stored in the DNA of the genes. There are 
approximately one hundred thousand genes 
in each cell of the human body. Although the 
genes are the same in every cell, each type of 
cell reads only certain genes. In this way a 
muscle cell, for instance, looks and works 
differently from a skin cell or a liver cell. 
There are two major types of cells in the 
human body, somatic (non-'reproductive) cells 
and germ line (reproductive) cells. Most cells 
in the body are somatic. Somatic cells 
proride all the body structures and perform 
all the functions e.xcept for passing genetic 
information on to the next generation. Germ 
cells include eggs in women and sperm in 
men. The genes in sperm and egg cells store 
information that will go to the next 
generation, to one's children. The genetic 
information in somatic cells is not passed on 
to the next generation. 
If the DNA information of a particular gene 
contains mistakes, the gene may not function 
properly. Sometimes the malfunction will not 
be serious, but other times it will cause a 
severe genetic disease. Examples of some 
genetic diseases are cystic fibrosis, sickle cell 
anemia, and hemophilia. Hemophilia, for 
instance, is cuased by the malfunctioning of 
the gene that makes the factor that causes 
blood to clot. As more is learned about 
human genetics, it is becoming clear that 
diseases such as diabetes, cancer, heart 
disease, and some manic depressive illnesses 
also result in part from faulty DNA 
information. 
For some genetic diseases, there are 
satisfactory therapies that do exist. Drugs, 
blood transfusions, changes in diet, or 
traiuplantation of body organs can often help 
to compensate for the incorrect information 
from the malfunctioning gene. For example, 
clotting factor can be administered to 
patients with hemophilia. 
Human gene therapy is a possible 
alternative approach to the treatment of some 
genetic diseases. The basic idea behind gene 
therapy is to iiuert normal genes with correct 
information into the DNA of the cells that 
contain malfunctioning genes. Adding genes 
V this way is called gene iiuertion. The 
added genetic information would allow these 
cells to function properly and might reduce or 
' eliminate the sigru or symptoms of the 
disease. For example, instead of repeatedly 
treating a hemophiliac with clotting factor, 
one could insert the correct genetic 
information into his cells to allow those cells 
to make their own clotting factor. 
It seems likely that human gene therapy 
will abo be used to combat certain diseases 
that may not be genetim For example, 
malignancies are usually treated with 
surgery, radiation and/or chemotherapy. For 
cancer patients who are not helped by these 
therapies, researchers are now planning to 
treat the patients' disease with genetically- 
altered white blood cells. 
Scientists have developed methods for 
inserting genes into human somatic cells. The 
techniquies for isolating human genes and 
making multiple copies of them in the 
laboratory are well established. Now 
scientists are studying how to insert those 
genes into cells and how to make those genes 
work properly once inside the cells. One 
. method for inserting genes into cells is to link 
the genes with a virus that has been crippled 
and rendered harmless. As part of the 
modification, such a virus, sometimes called 
a vector or vehicle, has been deliberately 
altered so that it can carry genes into cells 
but cannot then escape to infect other cells. 
After the cells to be treated have been 
temporarily removed from a patient’s body, 
the virus or vector is used to carry the 
desired gene into them. The final step will be 
to return the treated cells, which now contain 
the correct genetic information, to the 
patient’s body. For example, bone marrow, 
liver cells, or white blood cells could be 
removed from the body of a patient, treated 
in the laboratory, and returned to the patient. 
Whether bone marrow cells or some other 
tjTJe of human cells were used; the added 
genes would be inserted only into somatic 
(non-reproductive) cells and not into germ 
line (prcductive) cells. Therefore, newly 
inserted genes could not be passed to 
patients’ children. The therapy would be 
called somatic cell gene therapy and would 
not attempt to affect the germ line cells, 
which carry genetic information to the next 
generation. 
’The best outcome of human gene therapy 
would be a single treatment that would 
correct enough cells to provide a permanent 
cure for the patient’s disease. This kind of 
.complete success is unlikely in the beginning 
stages of human gene therapy but will remain 
the long-term goal of research scientists 
working in this field. 
PART 2— GOVERNMENTAL OVERSIGHT 
AND PUBUC PAR’nClPATION 
Oversight of government-funded 
experiments involving gene therapy for 
human patients occurs at both the local and 
national levels. 
At the local level facilities at which 
experiments would take place are required to 
have two types of committees. First, hospitab 
and universities involved in experiments with 
human subjects are required to have 
Institutional Review Boards (IRB) to ensure 
that the research complies with Department 
V of Health and Human Services (DHHS) 
regulations for protection of human subjects. 
Second, experiments that involve gene 
insertion must be approved in advance by an 
Institutional Biosafety Committee (IBC). 
These local review boards provide an 
opportunity for the general public to become 
involved in the decisions made about 
research involving gene therapy for human 
patients. The DHHS regulations require that 
at least one nonscientist serve as a member 
of each IRB. Further, the NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules encourage research facilities to 
open their IBC meetings to the public. 
At the national level the Director of the 
NIH must approve each human gene therapy 
proposal. In making this decision, the 
Director seeks advice from' the Recombinant 
DNA Advisory Committee (RAC). The initial 
review of the proposal is performed by the 
RAC's Human Gene Therapy Subcommittee, 
which is guided by the Points to Consider in 
... 'the Design and Submission of Protocols for 
the Transfer of Recombinant DNA into the 
Genome of Human Subjects, discussed later 
in this brochure. 
'.The general public is represented on the 
RAC and the Human Gene Therapy 
Subcommittee, as well as on the local review 
boards. The membership of the RAC (25 
— ' people), and of the Human Gene Therapy 
Recombinant DNA Research, Volume 14 
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