The Stem Cell Controversy

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The Stem Cell Controversy

• Robbie Majzner, Legislative Advocacy

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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
• The stem cell can divide over and over and remain
  in this undifferentiated state.
• This is why you hear a lot about stem cell
  "lines."
•  
• 3) CONTROVERSY
• No matter what, they seem to cause controversy

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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
  (--gt 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

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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

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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

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Induced Pluripotent Stem Cells

• In 2006, researchers in Japan successfully
  inducted mouse somatic cells to become
  pluripotent stem cells
• pluripotency depends on transcription factors
• 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

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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

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Divided Government, Republicans Chime in...

• Newt Gingrich

• Jay Dickey (AK)

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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)

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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

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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

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

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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 where
• The derivation process was initiated prior 8/9/01
• must have been derived from embryo that was
  created for reproductive purposes was no longer
  needed.
• Informed consent must have been obtained 
• Seen as a compromise by much of the media, but
  heavily criticized by liberals and the scientific
  community

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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

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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

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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 gt50 of
  conservatives)

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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

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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

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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
  research
• 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

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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."

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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

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Future Options...

• Unclear how this case will be decided
• Plantiffs, who claim, irreperable harm not
  clearly damaged by this policy
• Policy may not violate law, was accepted by both
  Republican and Democratic administrations
• 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

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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

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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