The Stem Cell Controversy

Robbie Majzner, Legislative Advocacy

Quick Review: What are the characteristics of a stem cell?1) POTENCY• The ability to differentiate into any type of cell in

response to cell signaling• Pluripotency: This is why stem cells have the

potential to "cure any disease" 2) SELF RENEWAL

o The stem cell can divide over and over and remain in this undifferentiated state.

o This is why you hear a lot about stem cell "lines." 3) CONTROVERSY

o No matter what, they seem to cause controversy

Types of Stem Cells: Somatic/Adult

• Cells that come from human sources that have some measure of multipotency (usually less so than embryonic, but can be made pluripotent)

 • Sources include bone marrow, cord blood, teeth (-->

hepatocytes), neural cells, skin, and more • Used in bone marrow transplant (allogenic or

autologous), tendon/ligament injury in horses, and in 2008, used to regenerate a section trachea that was transplanted into a woman

 • Used to be without controversy but have now

stepped into the limelight

Embryonic Stem Cells• Derived from Embryos, thus the controversy of when

life begins • Harvested from embryos at the blastocyst (day 5)

stage• PLURIPOTENT• Express transcription factors that suppress

differentiation • Cells that survive growth/harvesting process can

become pluripotent stem cell lines

Embryonic Stem Cell Uses

FANTASY

• Spinal Cord Regeneration

• Traumatic Brain Injury• SC+ Cloning = New

livers for everyone, no risk of rejection

• Extra limbs• New islet cells in DM1• Post MI, heart

remodeling • Replacing SN cells in

Parkinson's

REALITY 

•  A single Phase 1 trial of injecting stem cells into spinal columns of patients with acute spinal cord injury approved in 2009, but held due to safety concerns until July 2010

Induced Pluripotent Stem Cells

• In 2006, researchers in Japan successfully inducted mouse somatic cells to become pluripotent stem cellso pluripotency depends on transcription factors o retroviruses used for introduction of these TF's

• First successfully performed in human cells by same group at University of Wisconsin who first isolated hESC in 2007 and the same group in Japan in 2007

• Possible problems with this cell is retrovirus that randomly inserts could interrupt tumor suppressor genes

• Current research focusing on using protein only induction

• Promising field as avoids the controversy of embryonic SC

The History of Embryonic Stem Cell Politics & Research

• 1981: First Embryonic Stem Cells are isolated from mice (Camridge, UK and UCSF)

•  1995: Accomplished in Primate (Rhesus Monkey) in Wisconsin

• 1995: NIH Human Embryo Research Panel recommends federal government fund research using BOTH embryos left over from IVF  and on embryos created for experimentation

• Bill Clinton, citing ethical concerns, seeks middle ground and by executive order to HHS/NIH declines to fund research on embryos created for experimentation

Divided Government, Republicans Chime in...

Newt Gingrich Jay Dickey (AK)

The Dickey Amendment, 1995

• Despite Clinton's opinion, Congress intervened and passed the Dickey Ammendment "banning stem-cell research"

• Passed as a Rider on other legislation, every year since 1997, prohibits HHS/NIH funding for:

(1) the creation of a human embryo or embryos for research purposes;  or

2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death...

• Illegal for government to fund, but not for private citizens to carry out research (some European countries ban all)

Research Continues...(privately)

• In '98, two groups w/private funding successfully harvested HUMAN EMBRYONIC STEM CELLS (Hopkins, U. Wisconsin)

• Brought to limelight, so Clinton reconsiders his position

•  In 1999, the president's National Bioethics Advisory Commission again recommended that hESC harvested from embryos discarded after IVF treatments eligible for federal funding but Dickey stands in his way

Legal Cover

• Chief Counsel for the Department of Health and Human Services Harriet Rabb (now at Columbia Center for Bioethics) writes a legal opinion in 1999 that changes the Clinton Administration opinion and determines US policy for 10+ year

• Government cannot fund any destruction of embryos but can fund the research once the stem cells are created

• Creative work around accepted by Clinton Administration but called "Legal Sophistry" by Republicans at the time

Clinton and NIH Setup to start funding in 2000/2001, but....

The Bush administration puts a hold on all NIH funding in January 2001...• Tommy Thompson, the new head of Health and

Human Services, instructs the NIH to suspend the reviewing of all grants involving hESC

• President Bush took seven months to issue his decision regarding stem cell research in a TV speech that was supposed to be one of the biggest decisions of his term

The Bush Stem Cell Decision, 8/9/01• Similar to Clinton's decision, the NIH could fund

research on stem cells after they were created (no funding embryo destruction)

• Unlike Clinton's decision, these funds could only support research on already established stem cell lines whereo The derivation process was initiated prior 8/9/01o must have been derived from embryo that was

created for reproductive purposes & was no longer needed.

o Informed consent must have been obtained • Seen as a compromise by much of the media, but

heavily criticized by liberals and the scientific community

The Stem Cell Lines

• Initially thought to be 77 cell lines available world wide (from labs in US, S. Korea, India, Sweden, Israel, and more)

• Turned out there were only 21 available • Some cell lines were contaminated, others had

genetic mutations!• Criticized as not genetically diverse• Put a lot of money/power in the hands of those that

owned these lines• Engendered controversy throughout the Bush

presidency and became a big issue in the 2006 and 2008 elections

During Bush, the states speak out...• Several states put their own money into stem cell

research• 2004: NJ legislators pass a state budget that includes

$9.5 million for a newly chartered Stem Cell Institute of New Jersey

• 2004: California Proposition 17 authorizes the state to spend $3 billion on embryonic stem-cell research over 10 years, making it a larger funder than the federal govt. 

• Efforts also in IL, FL, CT, Iowa and others

Congress considers relaxing the restrictions...• After initial victory in 2004, there was significant

weakening of the Republicans and Conservatives in congress

• Stem Cell research a hot button issue in '06/'08 campaigns

• State funding as well as celebrities like Christopher Reeve helped bring this issue to the forefront of the media 

• 2005 poll, 70% Americans favored loosening the Bush restrictions (including >50% of conservatives)

But Bush sticks to his guns...

• President Bush used his first ever veto in July 2006 to veto a bill that would have increased federal funding for other stem cell lines

• Bush vetoed only 12 bills in his 2 terms as opposed to 44 for Bush 41 in 1 term and 37 for Clinton in 2 terms

• Of those 12 bills, only 7 did not become law• 3 of those 7 bills were for increased stem cell

funding

Democratic Takeover/Obama '09

• Obama campaigned promising to increase Federal Funding for Stem Cell Research

• In his first 100 days, Obama reversed the Bush restrictions, but also signed an appropriations bill extending the Dickey Amendment, thus returning policy to that under the end of the Clinton Administration

• In the years between Clinton and Obama, many other stem cell lines were created by private industry, total now ?75

• Obama did not legalize government funding of the creation of new hESC lines

Sherley v Sebelius, August 2010

• James L. Sherley and Theresa Deisher, two Adult Stem Cell researchers, brought suit in federal court against HHS to protest the funding of hESC research over aSC research

• They maintain that original intent of the Dickey Amendment was to prohibit all research on destroyed human embryos

• U.S. District Judge Royce Lamberth (DC Appelate) issued a preliminary injunction on funding hESC researcho If one...piece of research of an ESC research project

results in the destruction of an embryo, the entire project is precluded from receiving federal funding

• This was a temporary injunction, case not yet decided

The plaintiffs and their backing

• The two scientists were represented by The Alliance Defense Fund:

"a servant organization that provides the resources that will keep the door open for the spread of the Gospel through the legal defense of religious freedom, the sanctity of life, marriage  and the family."

• Sherley was formerly at MIT; when denied tenure, he went on a hunger strike and claimed racial bias:

“When I say ‘embryoism,’ I mean discriminating against human embryos, just like there is discrimination against people of different culture and races,” he said."

NIH/HHS Response

• Initially the NIH said they would stop all further funding of projects until the lawsuit was resolved but current grantees could continue research

• Appeal to Judge Lamberth for a stay of the injunction was rejected

• One week later, an appeal to the DC Court of Appeals granted an administrative stay of this injunction, returning federal funding to the initial Obama policy

• Now the court is hearing full arguments in Sherley v Sebelius before determining policy

Future Options...

• Unclear how this case will be decidedo Plantiffs, who claim, irreperable harm not clearly

damaged by this policy o Policy may not violate law, was accepted by both

Republican and Democratic administrationso If government loses, would likely mean a stop to

all federal funding of hESC research• Appeal to US Supreme Court • Legislative option to repeal or not renew the Dickey

Amendment• State by State funding

Get Involved

• Embryonic Stem cells, while they have little practical application today, have the potential to help cure and understand many congenital and acquired diseases.

• AAP Statement:   Research using human embryos and pluripotent

stem cells is of sufficient scientific important that the NIH should fund it and...federal oversight is morally preferable to the currently unregulated private sector approach.

• Write your senators and congressmen to repeal the Dickey Amendment

• Be an advocate for scientific research in your own states,  state pressure changes the action of the Federal govt

Possible Compromises...

• Repealing Dickey would allow for funding of destruction of embryos by the federal government, which may not be universally acceptable...Other possibilities:

 • Ammend the Dickey Ammendment to reflect the

Clinton/Bush/Obama understanding• Induced Pluripotent Stem Cells• Return to Bush era policy with a renewal of the date

after which we can use the stem cell lines to incorporate more lines