Stem Cells Technology, business, & ethics By Steve Mushero Swedish-American Chamber of Commerce & Silicon Vikings

11/14/02Stem Cells - Swedish-American Chamber of Commerce2 Overview A little about Stem Cells What are they good for ? Latest news, cool research Swedish contribution Ethics and the big issues How can we make money ? Future

11/14/02Stem Cells - Swedish-American Chamber of Commerce3 What are stem cells ? Stem = Root = Source Stem cells are the source of all cells Some stem cells can become any cell type Eventually differentiate to 200 cell types Very complex, poorly understood process Several stages of differentiation Stem, blood, red blood,... Reversible ? Yes, no, maybe, perhaps, don’t know

11/14/02Stem Cells - Swedish-American Chamber of Commerce4 Where are the Stem Cells ? Two choices – Embryo & Adult Embryo Start with one single cell - the fertilized egg !! Most flexible - can become any cell type Two choices of embryo source Fertilized in the usual way (Man & Woman) Cloned (use your own cells) Adult Present in normal tissues, including brain Have significant and poorly understood limitations

11/14/02Stem Cells - Swedish-American Chamber of Commerce5 Getting Embryonic Stem Cells Need an embryo Old fashioned way - With egg & sperm In Vitro Fertilization Most common Excess embryos (usually dozens created) Never implanted, so not aborted Fetal (Abortion) – Used for some R&D Therapeutic Cloning More exciting – allows use of own cells Needed to eliminate rejection Not reproductive cloning Move in Congress to ban therapeutic cloning

11/14/02Stem Cells - Swedish-American Chamber of Commerce6 Getting Embryonic Stem Cells Egg divides - first 2 cells, then 4, then 8... Becomes “Blastocyst” Hollow ball with key cells inside Harvest at 3-5 days – 30 cells in inner mass Embryo is destroyed in process, key ethical issue Two crucial embryonic cell characteristics Not yet differentiated (pluripotent) Can divide forever (key to culturing)

11/14/02Stem Cells - Swedish-American Chamber of Commerce7 Adult Stem Cells Extracted in VERY small amounts from normal tissues Key to avoiding rejection issues – your own cells Traditional rejection Graft vs. Host Disease – The Stems Attack ! Key to avoiding embryonic ethical issues Always partially differentiated (for now) BUT, research points to plasticity Liver stem cells to brain, muscle, and liver Bone marrow to muscle Brain stem cells to blood and muscle Not found in many key organs (Pancreas) Difficult to grow in culture; can’t mass produce Holy Grail - Is there a real master adult stem cell ?

11/14/02Stem Cells - Swedish-American Chamber of Commerce8 Using Stem Cells Reverse damage Central Nervous System (CNS) damage Parkinson’s Disease Multiple Sclerosis Heart Damage, Diabetes, Bone/Joint loss Cancer - Bone marrow transplant avoidance Fix genetic problems !! Severe Combined Immune Deficiency (SCID) Chronic Granulomatous Disease (CGD) Make good cells as needed ! Make whole organs as needed ! Kidney, Liver, Pancreas, maybe a Thumb

11/14/02Stem Cells - Swedish-American Chamber of Commerce9 Recent Research Three ongoing key focal points Understand basic processes, especially differentiation Differentiation triggers Expand uses (usually embryonic & cloning) Brain – Lots of progress, especially in dopamine, neurons Blood – Lots of immune system work Bones / Joints Pancreas (Diabetes) Liver – Cells come from marrow ? Weekly announcements – eyes, veins, heart muscle, skin Improve Adult Cells - Transdifferentiating / Plasticity Found a receptor/protein that limits plasticity (GCNF) Stanford found in Sept they cannot make other cells from adult blood stem cells How do adult cells work – fusion, division; Cancer risk ??

11/14/02Stem Cells - Swedish-American Chamber of Commerce10 Treatment Progress Modest to date – Very early in clinical process Parkinson’s injections Mixed, but promising results Last week - Got neural stem cells to make dopamine Multiple Sclerosis Treat by killing own rogue stem cells Israel in June 22 month old infant with immune system failure (SCID) Cured via repaired bone marry stem cells Mouse research this year Extract and fix cell DNA Clone cells to get embryonic stem cells Inject new stem cells to fix immune system

11/14/02Stem Cells - Swedish-American Chamber of Commerce11 Fixing an Immune System Baby with damaged immune system Remove bone marrow stem cells Fix genetic problem in DNA Culture cells to get useful volume Inject new immune cells into baby Normal immune system results !! Works when you have stem cells Mouse Immune Research - Cloned embryonic cells Remove ANY cell Fix DNA problem Clone cells to produce embryo/blastocyst Harvest stem cells Coax to differentiate into immune cells Inject new cells Crucial when body has no usable stem cells

11/14/02Stem Cells - Swedish-American Chamber of Commerce12 Swedish Stem Cell Research Leading stem cell research center Over 30 teams, 300 people 38% of NIH approved cell lines (25 lines) Main centers - Karolinska, Sahigrenska, Lund Work in all areas – embryonic, adult, cloning Legally favorable Therapeutic cloning allowed No embryonic issues Many research firsts Adult neural stem cell discovery First human embryonic stem cell cultures Number 1 or 2 per capita in patents, startups, biotechs, R&D spending, researchers, funding

11/14/02Stem Cells - Swedish-American Chamber of Commerce13 Swedish Companies Cell Therapeutics – Therapies and broad stem cell applications Neuronova – Adult neural stem cells for Parkinson’s NsGene – Neural stem cell therapies Vitrolife – IVR and fertility system supplier

11/14/02Stem Cells - Swedish-American Chamber of Commerce14 Ethics – What’s Wrong ? Most issues surround Embryonic Stem Cells Embryo cannot survive cell extraction When does life begin ? What is an Embryo ? Does it matter if it’s cloned (no sperm) ? Does it matter if not implanted (not aborted) ? Is it okay if IVF embryos discarded anyway ? Abortions also a source and worry Will we harvest humans ? Already having kids for marrow matching But, must abort for stem cells (cord blood ?)

11/14/02Stem Cells - Swedish-American Chamber of Commerce15 President Bush Chooses Balance scientific needs versus ethical & religious issues Federally funded scientists may work only with existing lines Cannot create any new stem cell lines (kill no embryos) Bottom Line - 78 cell lines are now in registry (27 in USA) 14 approved sources in 6 countries - UCSF has 2 lines 25 lines in Sweden, mostly in early stages (3+ ready) University of Gotenborg had 50 other Blastocysts, but rejected because embryo not yet destroyed 90% of mouse work over 20 years with only 5 lines Controversial Sufficient diversity Quality and purity issues Licensing, access issues Federal funding issue only Allows considerable private research and new lines Co-mingling decision – Allows mixed use in same lab – Big deal

11/14/02Stem Cells - Swedish-American Chamber of Commerce16 Business / Future Significant funding for basic research Very International – Sweden, US, India, Israel, Korea Massive promise in many of the most serious diseases Opportunities all along the development tree, in many specialties Suppliers, tools, equipment, reagents Stem cell sources (extraction from fat, etc.) Registries for matching (bone marrow) Processes for differentiating Actual therapies using cells (like drugs) Actual therapies targeting cells Entirely new views of the world

11/14/02Stem Cells - Swedish-American Chamber of Commerce17 Future of Stem Cells Immense promise, though much work remains Therapies beginning to emerge – SCID, Parkinson’s Embryonic cells from cloning No actual embryo, reduced ethical issues Adult stem cells will work eventually Eliminate need for embryonic cells & ethical issues Tremendous progress with applications Repaired genetic defects, maybe in womb New therapies for non-genetic diseases (Heart) New organs Repairing genetic defects will be common Change brown hair to blonde ? Ethics, ethics, ethics...

11/14/02Stem Cells - Swedish-American Chamber of Commerce18 Thanks & Questions Steve Mushero Swedish – American Chamber of Commerce & Silicon Vikings