Q&A on Stanford’s Stem Cell Research Announcement

? Work that does not involve stem cells
? Work that involves adult stem cells
? Work on new stem cell lines that the institute may develop

This Q&A is intended to help clarify how any potential new stem cell lines would be developed, how that work would be funded, how that work is different from reproductive cloning, and how those cell lines would be used to study human diseases.

Q: Is Stanford planning on cloning human embryos?
A: No. The new institute will study adult stem cell lines generated from individuals with specific diseases such as cancer or neurodegenerative disorders. The institute will also investigate two different ways of generating new embryonic stem cell lines ? initially in mice. This may be extended to human cell lines if the techniques prove useful.

? The first method involves inserting the nucleus isolated from an adult cell into a cell from an existing embryonic stem cell line that has had its own nucleus removed. By using a nucleus with the genetic information that predisposes an animal to develop certain genetic diseases, the researchers will create new stem cell lines to study the development of these diseases.
? The second method involves inserting the nucleus isolated from an adult cell into an unfertilized egg that has had its nucleus removed. The researchers will then stimulate the egg with the new nucleus to divide seven or eight times before removing some cells (called pluripotent stem cells) that have the potential to become many different types of cells in the body.

The second method is sometimes called therapeutic or biomedical cloning. Confusion, especially among the lay public, arises when this is referred to as “human embryonic cloning.” In fact several different national science and medical institutions (including the National Academy of Sciences) as well as President Bush’s own bioethics review panel, have determined that “human embryonic cloning” is an inaccurate and misleading term for this research. The approved term is “nuclear transplantation (or transferal) to produce human pluripotent stem cell lines.” This research is endorsed by these organizations as a necessary step in the development of novel new therapies for cancer, diabetes, Parkinson’s disease and others.

Once researchers recruited to the institute determine which of these techniques is most successful in mice, they will use that technique to create new human embryonic stem cell lines to better study human diseases. No one at Stanford is currently attempting to create new human embryonic stem cell lines.

Q: How is this different from cloning humans/making new babies?
A: Human embryonic cloning, or reproductive cloning, is an effort to create new humans with genetic material identical to the donor. Researchers at Stanford are unanimously and unambiguously opposed to human cloning for reproductive purposes. The second method using eggs with donor nuclei allows seven or eight cell division cycles (creating a ball of about 150 cells). This is the same first step as in reproductive cloning. However, and very importantly, the difference is that in generating a new stem cell line, cells are removed from the blastocyst and that blastocyst is destroyed. Neither the blastocyst nor the stem cell line can go on to become an adult human. In reproductive cloning, such as that used to create Dolly the sheep and other cloned animals, the blastocyst is put into an adult animal’s womb and is allowed to develop normally. Again, Stanford is opposed to human cloning for reproductive purposes.

Q: If human eggs are used, where will they come from?
A: It is far too early to predict the best method of generating new embryonic stem cell lines. If researchers decide to create the new cell lines by transferring the nucleus into an egg, they will assess bioethical concerns and review any new legislation to determine the best method with which to proceed. The institute will not use any human eggs, embryos or subjects without a thorough review process and without the individual’s fully informed consent. No biological materials ? eggs or embryos ? that Stanford currently has in its possession will be used in this research.

Q: How will these new stem cell lines be different/better than existing lines?
A: About 70 existing human embryonic stem cell lines are said to exist around the world. While these lines may be useful for general research, they are not disease-specific. By creating human embryonic stem cell lines that contain the genetic information that predisposes an individual to develop a specific disease, scientists can study the multi-step progression of that disease in many different tissue types. Scientists from around the world, as well as Stanford, have identified this line of research as a critical part of developing therapies for diseases including cancer, neurodegenerative diseases, diabetes and others.

Q: What is the legal status of this research?
A: There are currently no restrictions on the types of research that can be conducted on mouse embryonic stem cell lines. At this time, no federal laws prohibit creating new human stem cell lines, although federal money cannot be used to generate those lines. When, after several years of research in mice, scientists at the institute deem it appropriate to try similar technology in human cells, they will comply with all federal laws in effect at that time.

Q: How will this research be funded?
A: Current restrictions prohibit the use of any federal funds to create new human embryonic stem cell lines; however private funds can be used for this purpose. Recent California legislation has also made state funding available for creating human embryonic stem cell lines.

Laboratories must already account for how they use different public and private funds. The institute is prepared to fully account for the usage of funds in the creation of human embryonic stem cell lines (if and when that is done), ensuring that only private monies are used for this purpose.

Q: What’s special about this institute?
A: The ways of generating embryonic stem cells discussed here are not new, and many different institutions have tried these techniques in animal cells. Similar techniques were used to create the approximately 70 human embryonic stem cell lines that are now available. What is new is the development of a multi-disciplinary institute that will marry the power of stem cell biology and cancer biology to create novel treatments for many different, devastating diseases including:

? Parkinson’s disease
? Lou Gehrig’s disease
? Cancer
? Diabetes
? Cardiovascular disease
? Autoimmune diseases
? Allergies
? Neurodegenerative disorders

The institute will build on the long-standing history of Stanford University School of Medicine, and Dr. Irving Weissman and other researchers, in the biology of cancer and stem cells.

Q: How will the cells be used to study disease?
A: Like cancer cells, stem cells are able to divide indefinitely. Most other cells in the body lose this ability during development. Embryonic stem cells are special because they are pluripotent ? able to produce many different kinds of tissues.

Researchers at the institute hope to study the steps that occur as embryonic stem cells divide and from that learn more about how these cells are different from normal adult cells. This work will help researchers understand and block the uncontrolled division that occurs in cancer cells.

Other embryonic stem cells that carry DNA with disease-causing mutations can help researchers understand how that mutation leads to disease. For example, they may learn more about how that mutation causes the cell to become diseased, or how the protein made by the mutated gene fails to function properly. By understanding the molecular basis of the disease, the researchers may be able to generate drugs or therapies that make up for the genetic defect and treat the disease.

Finally, stem cells themselves may be used as a treatment for disease. One example of this is in bone marrow transplant. By using stem cells rather than donor bone marrow cells to reconstitute the bone marrow of cancer patients who have received very high doses of chemotherapy, it may be possible to treat cancer more effectively and eliminate the need for long-term treatment with anti-rejection drugs.

Q: Where can I learn more about the differences between nuclear transplantation and human reproductive cloning?
A: The National Academy of Sciences has two published reports on the topic available online:

? Scientific and Medical Aspects of Human Reproductive Cloning http://www4.nas.edu/news.nsf/isbn/0309076374?OpenDocument
The panel’s full report is also available at: http://www.nap.edu/books/0309076374/html/. The executive summary on pages 1-18, as well as Chapter 2 “Cloning: Definitions and Applications” may be particularly helpful

? Stem Cells and the Future of Regenerative Medicine http://www4.nationalacademies.org/news.nsf/isbn/0309076307?OpenDocument
The panel’s full report is also available at: http://www.nap.edu/books/0309076307/html/

? In addition, the Federation of American Societies for Experimental Biology ? a federation of 14 national scientific societies ? has published a question-and-answer sheet on the topic:
http://www.faseb.org/opa/ppp/q_and_a.html