H 1 uman Embryonic Stem Cells 1
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Human Embryonic Stem Cells - and Politics
October 16, 2007

I. Therapeutic Cloning involves the creation of a blastocyst via somatic cell nuclear transfer (cloning) from an animal (i.e.: a person) with a disease, to derive hES cells immunologically identical to donor, in hopes of treating the disease. The cloned blastocyst would exist only until day 5, when it would be used to isolate hES cells.

  • The nucleus of a somatic cell from the donor would be removed and placed into an enucleated human egg.
  • "Fertilization" would be simulated with electric shock.
  • The inner cell mass would be removed from the 5-day old blastocyst, which is genetically identical to the donor.
  • hES cells would be cultured into the tissue type needed by the donor.
  • This immunologically identical tissue would be placed back into the donor, curing or treating the donor's disease



The ethical dilemma:

The blastocyst, which is fully capable of developing into into a baby (if successfully implanted) , is grown only for 5 days and then destroyed = used to derive embryonic stem cells.

 

(Just one) Potential application of therapeutic cloning:
October 2003: Research Shows Therapeutic Cloning Can Cure Parkinson's-like Disease In Mice Nature Biotechnology, October 2003 Volume 21: 1200 - 1207

Several interesting new developments about our little pluripotent friends that boggle the mind:

  • 1) May 2, 2003: "Derivation of Oocytes from Mouse Embryonic Stem Cell". Karin Hübner and colleagues "developed a way to generate unfertilized eggs, known as oocytes, from mouse embryonic stem mES cells. " If the same procedure could be done with hES cELLS (make oocytes) scientists would have a ready source of oocytes that would be needed for personalized therapeutic cloning".

  • 2) Jan 8, 2004; Derivation of embryonic germ cells and male gametes from embryonic stem cells, Nature 427, 148 - 154 Niels Geijsen et al. Yes, these little wigglers from mES cells can actually fertilize eggs and produce early embryos. May be a new way to treat male infertility?

  • 3) May 9, 2005; Altered nuclear transfer (ANT) Rudolf Jaenisch and Alexander Meissner: 'the cdx2 gene essential for trophectoderm (--> placenta) differentiation is turned off before nuclear transfer. The resulting egg grows into a normal ball of cells called a blastocyst from which ES cells can be derived, but the deactivated gene means that the ball lacks the ability to implant in a uterus and so develop into a baby' (What do YOU think of this?). 

  • 4) Oct 17, 2005 (Mice) and Oct 26, 2006 (Humans) Robert Lanza/ Advanced Cell Technology Human embryonic stem cell lines derived from single blastomeres [PDF] [Humans - PDF] - derived hES cells from 8-cell state blastomeres - and showed that the remaining 7 cells could potentially develop into a healthy mouse, in the same way that PGD is done today

Politics

Is therapeutic cloning of humans currently legal in the US?
Is reproductive cloning of humans currently legal in the US?
Can federal research dollars (NIH) be used for either of these purposes?

Is therapeutic and/or reproductive cloning of humans currently legal in the world?

 

Various branches of government and their views on human cloning or hES research: 10 points to know! Note - this in no way includes all the legislation, but I have tried to include the bills that have either passed OR those that have repeatedly come up!

 
1995-1999
2000
2001
2002
2003
2004
2005
2006/7
Executive
2
3
5a
6
5b
10c, 10d
House
1
4
7a
7c,10a
7e;
Senate
7b
7d
10b
Private
1a
8a

8b; 8c
8d
Other
9a, 9b
9c

1995-2002

1) Preamble: The 1995 Dickey-Wicker Amendment: (Clinton Administration; Rep. Jay Dickey, R-Ark and Rep. Roger Wicker, R-Miss) Congress bans the use of federal funds for any experiment in which a human embryo is either created or destroyed, thus relegating all human embryo research to the private sector.

1a) James Thompson, John Gearhart, 1998, Geron, fell under Dickey-Wicker.

2) August 2000: The Clinton Guidelines: NIH / NBAC "hES cells are not a human embryo within the statutory definition - Dickey-Wicker does not apply. The NIH can allow federal funding of hES cell research".

  • Forbid the use of federal funds to destroy human embryos to derive stem cells but
  • Permit federal funding on stem cells already derived from surplus embryos (privately funded - like Thompson, Gearhart, and any new lines privately derived).
  • NO federal funding ever granted because... it was August 2000!


3) First Federal Legislation allowing federal funding of hES cell research - - the Bush 64- August 9, 2001: The President's Decision. See, he's ALWAYS been "the decider"! In his first address to the nation, Bush approves a compromise on stem cell funding. His decision allows for

(a) full federal funding for research on adult and umbilical stem cells,
(b) limited federal funding for research on human embryonic stem cells (hES cells) to pre-existing cell lines drawn from surplus embryos created for in-vitro fertilization,
(c) no federal funding for research on hES cells from Donor Embryos created specifically for developing stem cells or for research in therapeutic cloning

4) 3 Aug 2001: Weldon-Stupak, Round I: Human Cloning Prohibition Act of 2001 (HR 2505) (Dave Welson, R-FL, Bart Stupak D-MI) Bans all human cloning — for reproduction or research — and imposes a $1 million fine and a prison sentence of up to 10 years for violators. Passed by a vote of 265 to 162 in the US House of Representatives in 2001, after rejecting an alternative bill (H.R. 2608) [Jim Greenwood (R-Penn) and Peter Deutsch (D-Fla)] 178 to 249.

  • This so far (along with Weldon-Stupak Round 2, below) is the ONLY LEGISLATIVE VOTE ON CLONING !

A bit of "soapbox here" - just read ...

5) November 28, 2001: NBAC: Executive order 13237: Creation of The President's Council on Bioethics - 17 leading scientists, doctors, ethicists, lawyers, and theologians. Most prominent scientist and only biomedical research PhD is Elizabeth Blackburn, Professor, Department of Biochemistry and Biophysics, UCSF and former president of ASCB.

6) 28 January 2003: In his State of the Union Address, President Bush states to congress that "...because no human life should be started or ended as the object of an experiment, I ask you to set a high standard for humanity and pass a law against all human cloning."


7a) 28 February 2003: House Passes Ban on All Human Cloning: Weldon-Stupak (HR 534) Bans all human cloning — for reproduction or research — and imposes a $1 million fine and a prison sentence of up to 10 years for violators. H.R. 534 Passed, 241-yes, 155-no, 38-not voting. Again, stalled in the senate.

7b). 2003 Senate: prepared two rival bills, but neither had the votes to go forward:

2004: In the meantime, some significant private action....

8a) East Coast: 2001: Harvard, HHMI and Boston IVF began a collaborative research effort = therapeutic promise offered by human embryonic stem cells. Doug Melton, Andy McMahon, and Douglas Powers / Boston IVF

 

8b) 03 March 2004 Doug Melton, Harvard Professor and HHMI Investigator, derives 17 new hES cell lines "Derivation of Embryonic Stem-Cell Lines from Human Blastocysts" NEJM, 350:1353-1356 [PDF] (note: NOT cloned embryos - just hES cells from IVF blastocysts) using private funds from Harvard, the JDRF, and HHMI and excess, pre-implantation frozen embryos from Boston IVF. Melton makes these 'robust' cells freely available to all researchers (as long as they aren't using federal funds to do research on these lines, it is OK under the Bush Administration). Note: today, that number is at 28 stem cell lines - more than the true number of the "Bush 64" cell lines...

  • Written informed consent and approval by a Harvard IRB
  • 286 frozen and thawed cleaved embryos (6 to 12 cells each) were cultured to the blastocyst stage,
  • 97 inner cell masses were isolated, and
  • 17 individual human embryonic stem-cell lines (HUES1 through HUES17)
  • Son's disease propels a stem cell pioneer "Melton abandoned the work that had brought him tenure as a biologist at Harvard University and set out to cure juvenile diabetes, the disease that nearly took his son. 'I have done," Melton said, 'what any father would do.'"
  • Today 28 (40?) cell lines!

22 April 2004: Harvard Stem Cell Institute formed: "Seven Harvard schools, seven teaching hospitals, and close to 100 researchers and scientists are banding together in an ambitious new institute with a simple goal: to use stem cells to help the 150 million people nationally living with or dying from five types of organ and tissue failure."

  • Co-directors: Doug Melton and Harvard Medical School Professor David Scadden, (also director of Mass General's Center for Regenerative Medicine and Technology).
  • 5 diseases targeted: diabetes, neurodegenerative diseases, (Parkinson's disease, spinal cord injury);blood and immune diseases (leukemia, AIDS); cardiovascular disease, musculoskeletal diseases (DMD). Funding by private philanthropic donors, alumni, HHMI, JDRF and more (institute has now raised $26 million to date).

8c) 2 Nov 2004: West Coast: Arnold, Prop 71 (the California Stem Cell Research and Cures Initiative) passes 59% to 41% by statewide ballot

  • What is it? a CA bond proposal initiative ($3 billion in bonds and $3 billion in interest payments for 10 years) to create CIRM (California Institute for Regenerative Medicine) grants for stem cell research, research facilities, and other research. The first grant proposals were received on October 16, 2006 - $24 M in grants to be awarded shortly!
  • Who gets it? California researchers are eligible for ~$300 million a year in grants to work on hES cells from five-day-old human embryos.
  • Who monitors it? Governed by the ICOC (The Independent Citizens’ Oversight Committee), a 29 member panel of PhDs, patient advocates, lawyers, University administrators.
  • Update: Oct 13, 2006: California Stem-Cell Institute Unveils 10-Year Plan
    • $823 million is slated for basic research
    • $899 million for preclinical R&D
    • $656 million for clinical trials
    • $295 million for training and
    • $273 million for construction and renovation of labs to keep any ES cell work separate from facilities funded by the National Institutes of Health (NIH)
    • CIRM’s goals, according to the plan, are to generate a “clinical proof of principle” that ES cell therapy is able to “restore function for at least one disease" and produce 20 to 30 disease-specific cell lines.

8d) Oct 3, 2005: Midwest: Wisconsin National Stem Cell Bank to be Located in Madison: A $16 Milion NIH Grant to the NSCB, housed by the WARF offshoot WiCel (Director: James Thompson). "Having a centralized group helps to standardize not just the distribution of the cells but how they're grown, how they're tested and have one place where all the different cell lines can be tested under similar conditions," says Dr. Derek Hei, the UW director who led the effort to bring the bank to Madison.

...And news from other countries:

9a) 11 August 2004: Britain to allow cloning of human embryos "Britain (Newcastle Center) granted its first license for human cloning Wednesday, which is restricted by the Bush administration and which many scientists believe may lead to new treatments for a range of diseases."

 

9b) 28 September 2004: Dolly scientists' human clone bid - Ian Wilmut to clone cells for treatment of motor neuron disorder

9c) Human Cloning and World Politics! The UN General Assembly 59th Session - a few days of good ol' international fun

  • 19 October 2004 President Bush is continuing a push at the UN to ban both forms of human cloning -- for both reproductive and research purposes. On Nov. 6, 2003, the UN cloning ban lost by just one vote, 80-79. Two rival resolutions (2004):
    • Costa Rica’s draft calls for a treaty that would ban all cloning (backed by the Vatican and the Bush administration) while
    • Belgium’s draft = ban the cloning of babies, but allow therapeutic cloning
  • A vote on the proposal is expected Thursday, Oct 21, 2004."

  • 19 October 2004"George Bush's chief adviser on medical ethics, Dr. Leon Kass, accused Britain yesterday of crossing a "moral boundary" by allowing the cloning of human embryos. Dr Leon Kass launched his attack in an address to the conference ahead of a UN vote tomorrow which the Americans hope will lead to a worldwide ban on all cloning".

  • 19 October 2004! Response from our allies in England? "The United Nations should ignore a call by George Bush to ban all forms of human cloning." Therapeutic cloning has been legal in Britain since 2002. Lord May of Oxford, president of the Royal Society, the UK's national academy of science, said: "The US should be allowed to decide whether therapeutic cloning should be outlawed within its borders. But other countries, including the UK, have now passed legislation to allow carefully regulated therapeutic cloning while introducing a ban on reproductive cloning."

  • 24 October 2004 U.S. Stem Cell Policy Delays U.N. Action on Human Cloning "All 191 United Nations members agree on prohibiting reproductive cloning, but they are divided over whether to broaden the ban to cover therapeutic cloning. The Bush administration is aggressively seeking the total ban. That has set it against close allies like Britain and much of the world's scientific establishment.... By ignoring the fact that there is little likelihood of a consensus on therapeutic cloning research and pushing for a vote, the sponsors of the broader measure were effectively destroying the possibility of action on a ban on reproductive cloning on which all nations agreed. Vanu Gopala Menon of Singapore said progress on achieving that goal was being thwarted by countries that had "adopted an all-or-nothing attitude and paralyzed the process."

  • Indecision wins! 8 March 2005: U.N. vote urges human cloning ban" The UN has voted to approve a non-binding ban on all human cloning, ending two years of wrangling. The 191-nation assembly voted in favour of the declaration by 84 votes to 34, with 37 abstentions. The non-binding declaration was put to the vote after the UN had failed to reach an agreement on a binding ban. "It is a shame that the UN could not agree to a legally binding worldwide ban on reproductive cloning, simply because a small group of countries intransigently refused to allow individual countries to make up their own minds on therapeutic cloning."

The World of cloning

2005 - 2007: The Present

7) Revisited: 7c, 7d. 2005: but neither has come forward yet: Introduced for the 109th congress:

May 2005: Breakin' Away from Bush:

10a) May 24 2005: US House of Representatives passes the Stem Cell Research Enhancement Act H.R.810 (Rep. Michael Castle, D-DE) Immediately goes to

May 04 2005: Signed by Governor Mitch Daniels Senate Bill 268 (Public Law 126-2005) "Cloning. Declares that human cloning is against public policy. Prohibits using resources to knowingly participate in human cloning activities. Requires the state department of health to revoke the license of a hospital that knowingly allows human cloning activities. Requires the medical licensing board to revoke the license of a physician who knowingly participates in human cloning. Allows Indiana University to establish an adult stem cell research center. Defines adult stem cell and fetal stem cell and provides that research on these types of stem cells is not included in the definition of cloning. Makes:

  • (1) the unlawful participation in;
  • (2) the implantation of or the attempt to implant the product of; and
  • (3) the shipment or receipt of the product of;
  • human cloning a Class D felony.

Makes the purchase or sale of a human ovum, zygote, embryo, or fetus a Class C felony. Requires the state department of health to report to the legislative council concerning the feasibility of the state establishing an embryo adoption bank." Note: This bill had strong support from IU and the IU School of Medicine. "Members of the School's faculty and staff were instrumental in refining the language of the original bill in order to maintain the competitive integrity of stem cell research in the State of Indiana".

 

10b) First Presidential Veto, 2006:

  • May 24, 2005 (again): House passes the The Stem Cell Research Enhancement Act of 2005 [HR 810] that would have allowed expanded federal funding of stem cell research on lines of stem cells derived from discarded human embryos created for fertility treatments. The vote was 238 to 194

  • 21st April 2006 NIH stem cell chief resigns Mahendra S. Rao head of the stem cell group at the National Institute on Aging (NIA), has resigned his government post to join Invitrogen Corp, saying the US ban on federal funding of new embryonic stem (ES) cell lines posed a formidable barrier to his research goals.

  • 19 July 2006: Senate Approves Stem Cell Bill [HR 810]; Veto Is Expected "The Senate approved legislation t0 expand federal support of medical research using embryonic stem cells. White House officials said Mr. Bush planned to veto the measure as early as Wednesday, ignoring the substantial support it won from Senate Republicans, including the majority leader, Bill Frist of Tennessee. The vote was 63 to 37, with 19 Republicans joining all but one Democrat in support.
  • Where was Indiana?

  • 19 July 2006: First Bush Veto Maintains Limits on Stem Cell Use "By defying the Republican-controlled Congress, Mr. Bush re-inserted himself forcefully into a moral, scientific and political debate in which Republicans are increasingly finding common ground with Democrats. (Until Wednesday, Mr. Bush was among just seven presidents — all of whom served before 1881 — who had never vetoed a piece of legislation. Four served only partial terms; the other three were John Adams, Thomas Jefferson and John Quincy Adams"

  • HR 810 is the the first bill ever vetoed by George W. Bush, more than five years after his inauguration. The bill, which passed both houses of Congress, but by less than the two-thirds majority needed to override the veto. The House of Representatives then failed to override the veto (235 to 193) on July 19, 2006.

  • Election 2006: Oct 25, 2006: Michael J. Fox, Parkinson’s and Stem Cells Michael J. Fox Ad For Missouri's Claire McCaskill

And back to: 7e/f)

Coming up the pipeline! Stay tuned!

10c) Third Presidential Veto, 2007:

  • April 11, 2007 Stem Cell Research Enhancement Act of 2007 [S.5] = This bill would have amended the Public Health Service Act to provide for human embryonic stem cell research = similar in content to the vetoed Stem Cell Research Enhancement Act of 2005. The bill passed the Senate on by a vote of 63-34
  • June 8, 2007: House Votes to Expand Stem Cell Research: the Stem Cell Research Enhancement Act of 2005 passed on a vote of 247 to 176. The House bill received support from 210 Democrats and 37 Republicans, 35 votes short of what would be needed to override a presidential veto; 16 Democrats joined 160 Republicans in opposing the legislation. (nice graphic)
  • June 20, 2007: Bush Vetoes Measure on Stem Cell Research "President Bush on Wednesday issued his second veto of a measure lifting his restrictions on human embryonic stem cell experiments. The move effectively pushed the contentious scientific and ethical debate surrounding the research into the 2008 presidential campaign.
    • “Destroying human life in the hopes of saving human life is not ethical,” Mr. Bush said in a brief ceremony in the East Room of the White House. He called the United States “a nation founded on the principle that all human life is sacred.” More here
    • At the same time, Mr. Bush issued an executive order intended to encourage scientists to pursue other forms of stem cell research that he does not deem unethical. But that research is already going on, and the plan provides no new money. (June 2007: Biologists Make Skin Cells Work Like Stem Cells Yamanaka; Bush Will Pair Veto With New Cell Initiative; NY TImes)

 

Objectives


1. What is human Therapeutic Cloning? Why may this procedure be needed to realize the potential of hES cells?
2. Explain the interesting new developments about hES cells related to the Lanza paper the technique of Altered Nuclear Transfer (ANT)

3. Harvard Stem Cel lInstitute: Summarize the importance of Doug Melton - Boston IVF, HHMI, and the HSCI. Be able to explain the major findings of Melton's NEJM paper!

4. Prop 71: What is Prop 71 and what it its significance?

5. Legislation: Be able to state the major provisions and outcomes of:

 

Schedule