History of Stem Cell Research — A Timeline
Since the 19th century, scientists from all over the world have studied stem cells, from plants, to mice, to patients in search of a cure for their diseases.
1868 — The term “stem cell” appears in scientific literature, when German biologist Ernst Haeckel uses the phrase stem cell to describe the fertilized egg that becomes an organism, and also to describe the single-celled organism that acted as the ancestor cell to all living things in history. Read more.
1886 — William Sedgwick uses the term “stem cells” to describe the parts of a plant that grow and regenerate.
June 1, 1909 — Russian academic Alexander Maximow lectures at the Berlin Hematological Society on a theory that all blood cells come from the same ancestor cell. This introduces the idea of blood stem cells that are multi-potent, or have the ability to differentiate into several types of cells. Read more.
1953 — Leroy Stevens, a Maine scientist performing cancer research in mice, finds large tumors in their scrotums. These tumors, known as teratomas, contained mixtures of differentiated and undifferentiated cells, including hair, bone, intestinal and blood tissue. Researchers concluded the cells were pluripotent, meaning they can differentiate into any cell found in a fully grown animal. Read more.
February 2, 1963 — Canadian scientists Ernest McCulloch and James Till perform experiments on the bone marrow of mice and observe that different blood cells come from a special class of cells. This is one of the first pieces of evidence of blood stem cells.
1968 — Robert A. Good of the University of Minnesota performs the first successful bone marrow transplant on a child patient suffering from an immune deficiency that killed others in his family. The boy received bone marrow from his sister, and he grew into healthy adulthood.
1981 — Two scientists, Martin Evans of the University of Cambridge and Gail Martin of the University of California, San Francisco, conduct separate studies and derive pluripotent stem cells from the embryos of mice. These early cells are the first embryonic stem cells ever to be isolated.
Dec. 5, 1986 — Andrew Lassar and Harold Weintraub of Seattle, Washington, report results from an experiment in which they converted rodent fibroblasts (a type of connective tissue) directly into myoblasts (which generate muscle cells), using a single gene (MyoD). Being able to convert one type of adult cell into another may be important for regenerative medicine.
1989 — Research from scientists Mario Capecchi, Martin Evans and Oliver Smithies comes together, creating the first “knockout mice,” which are mice specially bred in the laboratory to be missing specific genes. These mice are created using embryonic stem cells and homologous recombination, a process in which similar strands of DNA switch genes. Since scientists bred the first knockout mice, there have been more than 500 different mouse models of human disease. In 2007, the Nobel Assembly recognized these three scientists for their research, which has proven to be invaluable in understanding how various human diseases, including diabetes and cancer, develop.
1997 — Dominique Bonnet and John Dick of Canada discover that leukemia comes from the same stem cells that make our blood cells. This is one of the first major studies to say that cancer grows out of stem cells gone off course, supporting the concept of “cancer stem cells.”
Nov. 6, 1998 — A team at the University of Wisconsin, Madison, led by James Thomson and Jeffrey Jones, reports the creation of the first batch of human embryonic stem cells, which they derived from early embryos. After finding the cells were pluripotent, the team sees the potential the cells have for drug discovery and transplantation medicine.
Aug. 9, 2001 — President George W. Bush signs an order authorizing the use of federal funds for research on a limited number of existing human embryonic stem cell lines. (Click here for the President’s remarks.) Scientists fear several of these available lines are now too old for research.
April 5, 2002 — A Whitehead Institute team that includes future Children’s Hospital Boston stem cell researcher George Q. Daley, MD PhD reports combining the use of gene and cell-based therapy to treat a mouse model of immune deficiency. Read more.
Dec. 10, 2003 — George Q. Daley and his team publish findings on converting stem cells from mice into germ cells and, eventually, primitive sperm cells that are able to fertilize egg cells. These embryonic germ cells give scientists a chance to study different processes, including cancer growth and the development of sperm cells.
May 19, 2005 — South Korean scientists under the direction of Woo-Suk Hwang announce that they’ve used therapeutic cloning to create 11 stem cell liness that match their donors, one year after reporting the creation of the first human stem cells with this method. The report excites the scientific community, since the immune systems of patients receiving their own stem cells are unlikely to reject the transplants, a common problem for donated organ transplants. However, the journal Science later retracts the Hwang paper, when it is revealed that the Korean scientists falsified their results. Researchers at Children’s show that one of the lines was actually created through parthenogenesis, a process in which a single egg cell is stimulated to divide without a sperm cell.
Dec. 15, 2005 — Yuan Wang, George Q. Daley, and other researchers at Children’s publish findings in which they dramatically improved the process of converting embryonic stem cells from mice into blood stem cells for transplantation.
Aug. 25, 2006 — Japanese scientists Shinya Yamanaka and Kazutoshi Takahashi announce the creation of rodent induced pluripotent cells (iPS cells). iPS cells are adult cells reprogrammed to look and function like embryonic stem cells, which makes them another valuable resource for stem cell research and eventual cellular therapeutics.
Dec. 14, 2006 – George Q. Daley and colleagues at Children’s report the creation of donor-matched embryonic stem cells in mice through parthenogenesis. (Read Children’s press release.) Parthenogenesis may prove to be an alternative to embryonic stem cells or therapeutic cloning. The team hopes to one day use patient-specific, parthenogenetic stem cells for therapies in their female donors, whose immune systems are unlikely to reject the cells.
November/December, 2007 — Three independent teams in Japan, Wisconsin and Boston, led by Shinya Yamanaka, James Thomson, and George Q. Daley, respectively, announce that they have created human iPS cells. The study in the Daley Lab at Children’s is the first iPS project to begin with a donor walking in and having a sample taken, rather than being generated from a frozen sample. Genetically matched to their donor, iPS cells would theoretically not be rejected by the immune system, an important advantage in transplantation medicine.
Aug. 6, 2008 – The Stem Cell Program at Boston Children’s Hospital announces the creation of 10 disease-specific lines of iPS cells. These cells provide scientists with laboratory models of diseases such as Down syndrome and muscular dystrophy, and will help them find innovative ways to understand, prevent and treat such diseases. (Read Children’s press release.) This work was recognized at the end of 2008 as contributing to the Breakthrough of the Year in Science magazine.
In the video above, George Daley is interviewed for a Science magazine video introducing cell reprogramming as its 2008 Breakthrough of the Year.
Aug. 27, 2008 — A team of scientists from Harvard and Children’s publish an experiment in which they turn a rodent pancreatic exocrine cell into an insulin-producing cell. Similar to the pioneering work of Andrew Lassar and Harold Weintraub from 1986, this experiment shows it is possible to reprogram one type of adult cell into another type of adult cell, skipping the intermediary step of creating iPS cells.
Jan. 23, 2009 — Geron Corporation announces the FDA’s approval for a limited phase I trial of Geron’s new treatment for spinal cord injuries. This was the first FDA approval of a clinical trial for a therapy based on human embryonic stem cells.
March 1, 2009 — Scientists in Toronto report the creation of iPS cells in their lab in a manner that is safer than previously used methods. These researchers are able to remove the genes necessary to reprogram an adult cell into a stem cell after the reprogramming step is complete.
March 9, 2009 — President Barack Obama signs Executive Order 13505 to repeal some of the restrictions on human embryonic stem cell research funds placed by the previous administration. The order requires the National Institutes of Health to draft new guidelines for federal funding policies within 120 days.
July 7, 2009 — The NIH issues the revised guidelines on federal funding for stem cell research. Included are strict provisions for informed donor consent and the ethical procurement of leftover embryos from in vitro fertilization.
May 2009 — Phase I clinical trials begin for PGE2, a known drug that Children’s researcher Leonard Zon discovered can increase production of blood stem cells. These trials are being conducted in leukemia and lymphoma patients who have been implanted with blood stem cells from donated umbilical cords. If the trials are successful, single doses of umbilical cord blood stem cells, combined with PGE2, may be a viable source for blood stem cells for adult patients who cannot receive a bone marrow transplant. Read more.
Dec. 2, 2009 — The NIH deems 13 lines of human embryonic stem cells, the first under the new administration’s guidelines, eligible for research funding. Eleven of these 13 lines were created at Boston Children’s Hospital. Any scientist wanting to conduct research on any of these cell lines can now apply for federal funding. Read more in this blog post.
Stem cells hold great promise and potential in the field of medicine, whether doctors inject them into patients to replace diseased bone marrow, or lab scientists scrutinize them under a microscope to see how lung cancer develops. The road to innovation is long and full of obstacles, and there are plenty of questions left unanswered. But progress is ongoing and in many cases startling. At Children’s Hospital Boston, researchers continue the journey to bring these advances to the clinic, ethically and safely.