Session I | Session II
Stem Cell Research
Ronald McKay, Ph.D.
Senior Investigator, National Institute of Neurological Disorders and Stroke
May 22, 2003
Mr. Chairman, Senator Harkin, and Members of the Subcommittee, I am pleased to appear before
you today to testify about human embryonic stem cell research. Human embryonic stem (ES) cells
have been proposed as a limitless source for the many specific cell types of the adult body.
Cells obtained in this way will likely have many uses in the future, including the development
of new cell therapies for degenerative diseases. There is wide agreement on the potential
importance of knowledge about stem cells but much of this information comes from work on mouse
ES cells. In the last few months, published reports have shown that mouse ES cells can generate
cells of the skin, blood, brain and pancreas. Even in the mouse system there are technical
questions we do not fully understand but there is no doubt that mouse ES cells can be used to
generate many somatic cell types.
There is clear evidence that human ES cells will form teratomas, complex mixtures of
different cells, but much less is known about efficiently generating specific cell types. There
are encouraging published reports of a preliminary nature but the research and biotech
communities still needs to demonstrate that human ES cells can rapidly generate large numbers
of a specific cell type of clinical interest. The recent wider access to human ES cells made
possible by the President's decision of August 9, 2001 will accelerate progress on this
question and I am confident that procedures for making some of the human cells that most
interest us will be reported in detail in the next few months.
As this area is new and rapidly developing, the major technical barriers that may slow our
progress are not understood. However, some of the potential difficulties can be anticipated.
The human ES cells may be difficult to grow and differentiate. Their genome may be unstable.
The different cells may show very different properties resulting from their genetic origin.
There may be unexpected difficulties in taking the cells to a point where they are clinically
relevant. And once we have obtained the differentiated cells, it may be difficult to integrate
these cells with the other cells of the body.
All of these possibilities may be influenced by the history of the cell line. There are
several variables that differ when human ES cells were first placed in culture by different
research teams around the world. But in the first wave of work most success was obtained by
growing the human cells in the company of a supporting mouse cell. This procedure was derived
from data showing that mouse ES cells grow well in the presence of another cell type, a
fibroblast. We do not know the exact reason for the effects of this interaction. Workers in
the field still actively discuss whether one or another type of mouse fibroblast is more
effective. Recent work suggests that the beneficial effects of mouse cells can be replaced by
human cells or by introducing specific chemicals into the environment that supports the
human cells. There are many possible ways that differences in the growth conditions could
influence the properties of the human ES cells. But there are two simple questions that must
be asked: Can we accurately measure these effects of these different growth conditions and do
they cause irreversible harm to the human ES cell lines?
The answer to the first question is yes, but as we have discussed above, we are still
developing the techniques to accurately measure all the interesting properties of human ES
cells. So today, we cannot compare precisely the properties of cells grown under different
conditions. A detailed answer to the second question depends on having access to these
techniques. However, it is clear that any major irreversible change would immediately influence
the use of an existing cell lines. The genome carries biological information through time so it
is important to establish if the ES cells carry alterations in their own genes or harbor genes
from other organisms that significantly affect their properties. Many cells carry pathogens
that would have no practical consequences but we are explicitly concerned that the human ES
cells have acquired significant genetic changes from any stage of their previous history.
These problems have been clearly stated by the biomedical research community in discussions
held by the NIH Stem Cell Task Force. The NIH response to these concerns is outlined in Dr.
Zerhouni's statement but it might be useful for me to amplify on the resources and role of the
Human ES Cell Characterization Unit that Dr. Zerhouni has asked me to direct. The ES Unit has
been established to directly compare the cell lines that are available on the NIH stem cell
registry. The groups holding intellectual property rights have agreed to allow the ES Cell
Unit to compare the available cells and provide open access to this information. Space has
been renovated, equipment is being purchased and we hope to have a core team of four scientists
at work in 3 or 4 weeks. We are building strong contacts with scientists in this country and
overseas to acquire additional eligible cells. This work is monitored by a committee that
includes senior investigators at other medical research facilities. This project has been
actively sponsored by Dr. Zerhouni, the Director of the Intramural Research Program, Dr.
Gottesman and Dr. Battey. We will compare ES cells with adult stem cells that may be
pluripotent and move quickly to analyze as many of the critical features of these cells as
possible. The genetic composition of these cells will be one of several measures that we use
to define the cells. Our immediate goal is to rapidly develop the Human ES Cell Unit as a
source of high-quality information that will allow informed use of these cells.
In this statement, I have placed the specific issue of mouse feeder in cells in the wider
context of characterizing human ES cells. New data confirms that human ES cells can
differentiate to cells of great clinical interest. We are all aware that there are many
potential sources of problems as we move forward with this exciting technology. Should we
find that the currently available cells carry irreversible changes that restrict their value,
this information will be discussed openly without delay. But this specific issue is only one
of many that we must address as we explore the potential of human ES cells. I am confident
that the National Institutes of Health, here in Bethesda, will contribute both technical
information and sound advice to the world-wide effort needed to harness the benefits of stem