June 1, 1909: Alexander Maximow presents a lecture at the Hematological Society of Berlin introducing the concept of stem cells as the common ancestors of cellular elements in the blood.
1959: First successful use of stem cell transplants in humans, in three separate studies all involving hematopoietic stem cells (HSCs). E. D. Thomas and colleagues use syngeneic grafts from identical twins to treat two leukemia patients, George Mathe and colleagues perform allogeneic (from a separate individual who is not an identical twin) bone marrow transplants on five patients accidentally exposed to irradiation, and McGovern and colleagues treat a leukemia patient with autologous (from the patient) bone marrow cells.
1963: E. A. McCullough and colleagues prove that stem cells exist in the bone marrow of mice and that HSCs have the key properties of self-renewal and could become any type of blood cell.
June 1966: R. J. Cole, R. G. Edwards, and J. Paul isolate embryonic stem cells (ESCs) from the pre-implantation blastocysts of rabbits.
1968: First successful use of bone marrow transplantation to treat patients with leukemia or hereditary immunodeficiency: success due to presence of HSCs in the marrow graft, which can reconstitute blood and immune systems after myeloablation.
1974: Congress imposes moratorium on federal funding for clinical research on embryonic tissue and embryos, which remains in place until 1993.
1981: Nature announces that two research groups, working independently, successfully derived embryonic stem cells from the inner cell mass cells of the blastocyst in mice; one group is led by Martin Evans at the University of Cambridge (UK), the other by Gail Martin at the University of California, San Francisco.
1987: Peter Hollands demonstrates the first therapeutic in vivo (in a living animal) use of ESCs: injection of ESCs restores lost bone marrow stem cells in lethally irradiated mice.
1988: Bone Marrow Donors Worldwide, a collaborative network of stem cell donor registries and cord blood banks, founded in Leiden (the Netherlands) to facilitate sharing of HLA phenotype and other information to physicians of patients who need a hematopoietic stem cell transplant.
1992: Y. Matsui and colleagues announce successful isolation of mouse embryonic germ cells, which have properties similar to embryonic stem cells.
January 1993: Newly elected president Bill Clinton instructs Donna Shalala, Secretary of the U.S. Department of Health and Human Services, to remove the ban on embryonic research.
1995: Congress bans federal funding for research on embryos, but leaves it unclear whether this ban applies to cells already derived from an embryo.
November 1995: James A. Thomson and colleagues at the University of Wisconsin derive the first non-human primate embryonic stem cells, from rhesus monkeys, suggesting that embryonic stem cells could also be derived from humans.
November 5 and 10, 1998: James A. Thomson at the University of Wisconsin, and John D. Gear-hart at Johns Hopkins University report almost simultaneously that they have successfully isolated human embryonic stem cells (hESCs). Despite the therapeutic potential of hESCs, which can become any type of cell in the human body and thus offer hope for currently intractable conditions such as Parkinson’s disease and spinal cord injury, the announcement is not without controversy due to the origins of the cells used in the research. Thomson’s team worked with cells from human embryos created in vitro (“in glass,” i.e., in the laboratory) while Gearhart’s team obtained their stem cells from human fetal primordial germ cells.
August 2000: The National Institutes of Health (NIH) legal department advices that NIH may fund research on cells derived from blastocysts, but may not fund the derivation of the cells themselves (which may be performed by private companies).
December 2000: Mouse experiments by Timothy Brazelton and colleagues at Stanford University discover that HSCs can transform themselves to neuronal cells, demonstrating a plasticity (ability to become other types of cells than blood cells) which could have important therapeutic implications). This research has been challenged on several grounds but research continues because of the ready availability of HSCs (every person could serve as their own donor, making hESCs unnecessary).
July 2001: The Jones Institute, a private infertility clinic in Norfolk, Virginia, announces that it has created embryos from donated gametes (reproductive cells).
August 9, 2001: President George W. Bush, in a speech on prime-time national television, announces federal research funding will be available for the first time for hESC research, but that such research would be limited to the estimated 60 preexisting stem cell lines.
November 2001: NIH invites proposals for stem cell research and releases a list of 74 acceptable stem cell lines; many of the lines are not suitable for human trials because they have been grown in mouse media.
November 25, 2001: Advanced Cell Technology, a private company in Worcester, Massachusetts, announces that it has cloned human embryos from adult cells, creating cells that are a perfect genetic match for the donor.
2002: The United Kingdom announces that stem cell research is a scientific priority and allocates an additional £40 million to support stem cell research.
January 2003: Nine funding agencies form the International Stem Cell Forum (ISCF) to encourage international collaboration and promote increased funding for stem cell research; as of January 2004,14 agencies from 13 countries have joined the ISCF.
2004: Annual Report of the International Bone Marrow Transplant Registry reports that over 27,000 patients annually are treated by blood stem cell transplantation, for various cancers, hereditary diseases, and bone marrow failure
March 2004: Hwang Woo-Suk and colleagues at Seoul National University announces in the prestigious journal Science that he successfully cloned patent-specific stem cells suing somatic nuclear transfer. Because the embryos were cloned in order to produce stem cells, rather than for reproduction, this reported success reopens the debate about therapeutic cloning (cloning cells for the purpose of treating human disease). Hwang’s previous research had been in genetically modified livestock, and he claimed to have successfully cloned two cows in 1999, although he provided no scientific data to back up this claim.
June 25, 2004: New Jersey becomes the first state to fund stem cell research, as legislators create the Stem Cell Institute of New Jersey and allocate it $9.5 million in state funding.
November 2, 2004: Partly as a response to federal research funding restrictions, California becomes the second state to allocate funding for stem cell research, as voters approve Proposition 71. This bill creates the California Institute for Regenerative Medicine, which is allocated $3 billion in taxpayer funding over 10 years.
January 1, 2005: Connecticut Governor M. Jodi Rell announces that she will recommend that the state budget include a special fund to support stem cell research in Connecticut. The state budget, passed in June, includes $100 million to support stem cell research over 10 years.
May 23, 2005: The Starr Foundation announces awards of $50 million to support stem cell research at Weill Medical College of Cornell University, Rockefeller University, and Memorial Sloan-Ket-tering Cancer, all in New York City.
May 31, 2005: The State of Connecticut Stem Cell Advisory Committee allocates $19.78 million in stem cell research funds to researchers from Yale, Wesleyan, and the University of Connecticut. These are the first grants from Connecticut’s Stem Cell Research Fund, which was created in 2005 and is charged with allocating approximately $100 million to support stem cell research by the year 2015.
June 2005: Hwang Woo-Suk and colleagues publish an article in Science claiming that they have created 11 human embryos from somatic cells from different donors. He claims to have developed a more efficient process that uses fewer eggs to create more hESCs.
July 13, 2005: Illinois Governor Rod Blagojevich issues an executive order which creates the Illinois Regenerative Institute for Stem Cell Research, which will award $10 million in state funds to support stem cell research. This makes Illinois the fourth state, and the first midwestern state, to allocate public funds to stem cell research.
August 18, 2005: Colin McGuckin, Nico For-raz and colleagues at Kingston University (UK) announce discovery of cord-blood-derived embryonic-like stem cells (CBEs), which appear to be more versatile than adult stem cells found in bone marrow, although less versatile than hESCs. This discovery could skirt ethical objections to hESC research with cells derived from embryos, because umbilical cord blood can be acquired without destruction of human life.
September 19, 2005: Brian Cummings, Aileen Anderson and colleagues at the University of California, Irvine, announce that they successfully used adult neural stem cells to repair spinal cord damage in mice. The mice receiving neural stem cells showed improvement in coordination and walking ability, suggesting the research may lead to therapies to aid humans with spinal cord injuries.
September 21, 2005: Floridians for Stem Cell Research and Cures, Inc., an advocacy group for stem cell research, propose a ballot initiative requiring the state of Florida to spend $200 million in state funds over the next 10 years in support of stem cell research. On September 23, Citizens for Science and Ethics, Inc., a group opposing stem cell research, files a petition which would amend Florida’s state constitution to prohibit embryonic stem cell research.
November 2005: Gerald Schatten a former colleague of Hwang Woo-Suk now at the University of Pennsylvania, announces there were ethical irregularities in Hwang’s procurement of oocyte (egg) donations used in his research. Roh Sung-il, a close collaborator, announces at a press conference on November 21 that oocyte donors had been paid $1,400 each for their eggs. On November 24, Hwang announces that he will resign from his post due to the scandal.
December 16, 2005: New Jersey becomes the first state to allocate public funds for hESC research, as a state commission grants $5 million awarded to 17 research projects, most located at the University of Medicine and Dentistry of New Jersey, Rutgers University, and Princeton University.
December 29, 2005: In South Korea, a Seoul National University investigation of Hwang’s scientific work concludes that all 11 stem cell lines claimed in his 2005 published paper were fabricated.
2006 (calendar year): Over 1,100 articles on ESC research are published, a nearly 10-fold increase from 140 in 1997.
January 11, 2006: Science retracts both of Hwang’s papers due to scientific misconduct and fraud. On January 12, Hwang holds a press conference to apologize but does not take responsibility for the fraud claiming that members of his scientific team sabotaged his work.
April 2006: Maryland allocates $15 million in state funding for ESC research, beginning in July 2006, through passage of the Stem Cell Research Act.
May 12, 2006: South Korea indicts scientist Hwang Woo-suk on charges of fraud, embezzlement, and bioethics violations. Three of his collaborators are also charged with fraud.
June 21, 2006: Florida Governor Jeb Bush, speaking at the annual biotechnology Industry Organization meeting, announces his disapproval of hESC research. Bush further announces that no stem cell research will be performed at any Florida university, nor at the Scripps Research Institute in Palm Beach.
July 2006: ES Cell International in Singapore becomes the first company to commercially produce hESCs that are suitable for clinical trials; vials of stems cells are offered for sale on the internet for $6,000.
July 18, 2006: Senate Majority Leader Bill Frist (R-TN) publishes an editorial in the Washington Post announcing his support of federal funding of stem cell research, in opposition to President Bush’s policy. Frist also announces that he sees no contradiction between stem cell research and his pro-life beliefs.
July 19, 2006: President Bush vetoes a bill, passed by the House in 2005 and the Senate in July 2006, that would expand federal funding for hESC research.
August 23, 2006: Scientists from the private company Advanced Cell Technology announce they have developed a technique which allows them to remove a single cell from an embryo. The embryo is not harmed in the process and the cell can then be grown in the lab, circumventing ethical objections to hESC research which requires the destruction of embryos.
November 7, 2006: Missouri voters pass Amendment 2, a constitutional amendment that states that any hESC research or treatment allowed by the federal government will also be allowed in Missouri. The narrow victory (51%-49%) galvanizes opposition to the bill, much of which is centered on their contention that it would allow human cloning.
November 28, 2006: In the wake of the Hwang Woo-Suk scandal, a panel lead by John I. Brau-man recommends changes in the procedures used to review papers submitted for publication in Science. The changes recommended include flagging high-visibility papers for further review, requiring authors to specify their individual contributions to a paper, and online publication of more of the raw data on which papers are based.
January 7, 2007: Dr. Anthony Atala of Wake Forest University and colleagues from Wake Forest and Harvard Universities report the discovery of amni-otic-fluid-derived stem cells (AFS), which seem to hold similar promise to hESCs. The researchers reported that AFS could be extracted without harm to mother or child, thus avoiding some of the moral controversies regarding hESCs.
February 28, 2007: Governor Chet Culver of Iowa signs the “Iowa Stem Cell Research and Cures Initiative,” a bill which ensures that Iowa researchers will be allowed to conduct stem cell research and that Iowa patients will have access to stem cures and therapies. The bill also prohibits human cloning.
March 31, 2007: New York passes a budget for the fiscal year 2008 that includes an appropriation of $100 million for stem cell and regenerative medicine research. The funds will be distributed through the Empire State Stem Cell Trust, which will be funded at $50 million per year for 10 years after the initial appropriation of $100 million.
April 11, 2007: Richard K. Burt and colleagues report success in treating type 1 diabetics in Brazil with stem cells taken from their own blood. The experimental procedure, reported in the Journal of the American Medical Association, has allowed the diabetics to stop taking insulin for as long as three years.
May 30, 2007: California Governor Arnold Schwarzenegger and Canada’s Premier of Ontario Dalton McGuinty announce an agreement between Canada’s International Regulome Consortium and the Stem Cell Center at the University of California, Berkeley, to coordinate research. McGuinty also announced the creation of the Cancer Stem Cell Consortium, which will coordinate and fund cancer stem cell research, and announced an initial donation of $30 million Canadian to the consortium from the Ontario Institute of Cancer Research.
June 6, 2007: Rudolf Jaenisch and colleagues at the Whitehead Institute, affiliated with the Massachusetts Institute of Technology in Boston, announce in Nature that they have succeeded in manipulating mature mouse stem cells so they have the properties of ESCs. In the same issue of Nature, Shinya Yamanaka and colleagues at Kyoto University announce that they have developed a method to reprogram stem cells in mice back to the embryonic state, so they may then develop into different body cells similarly to hESCs. If this technique is adaptable to human cells, it would allow researchers to bypass most of the controversy involved with the use of hESCs derived from human embryos.
June 20, 2007: President Bush vetoes legislation that would have allowed federal funding for ESC research using cells from embryos from fertility clinics that would be destroyed anyway. At the same time, Bush issues an executive order encouraging federal financial support of research aimed at creating stem cells without destroying embryos. The veto places him in opposition to most American voters and many members of the Republican Party. In response to the Bush veto, Democratic presidential candidates Hillary Clinton and Barack Obama pledge to support federal funding for hESC studies if elected.
August 3, 2007: Kitai Kim, George G. Daley and colleagues and Children’s Hospital, Boston, report in the journal Cell Stem Cell that Hwang Woo-Suk, the discredited Korean researcher, did have one significant research result which appears to be genuine.
The Children’s researchers determined that Hwang’s purposed ESCs were produced by parthenogenesis (virgin birth) from unfertilized eggs, a result since achieved by other researchers as well.
November 6, 2007: New Jersey voters reject a ballot measure which would have allowed the state to borrow $450 million to fund for stem cell research. Defeat of the initiative is attributed to the state’s worsening fiscal condition and a vocal alliance of conservatives, antiabortion activists, and representatives of the Catholic Church who oppose stem cell research.
November 14, 2007: Shoukhrat Mitalipov and colleagues at the Oregon Health and Science University’s national Primate Research Center announce in Nature that they have successfully derived ESCs by reprogramming genetic material from the skin cells of rhesus macaque monkeys.
November 20, 2007: The journals Cell and Science report on discoveries by two independent teams of scientists that reprogram human skin cells to have the characteristics of hESCs. One team is led by Shinya Yamanaka; the other is led by James Thomson of the University of Wisconsin, Madison.
2008: Rudolf Jaenisch and colleagues correct sickle cell anemia in mice using iPS cells.
January 14, 2008: Doris Taylor and colleagues at the University of Minnesota report success in creating a beating rat heart by injecting cells from newborn rats into the values and outer structure from a dead rat heart.
February 20, 2008: Scientists at Novocell, a private biotechnology company located in San Diego, announce that they have successfully used hESCs to control diabetes in mice whose own insulin-producing cells had been destroyed.
