Thank you for such an informative post on stem cells.
I am posting this on multiple threads, which I apologize for. It isn’t meant to be spam, but it is my own lengthy thoughts on stem cells, which I hope will help clarify some issues that are not widely understood, and that is the reason I’m doing it.
Since Bush’s decision to provide federal funding for human embryonic stem cell (hES) research using existing hES lines, I’ve been debating within myself what that decision means to investors and potential investors in companies associated with adult or embryonic stem cells. I thought I’d post my current thoughts, by no means final. Disclosures: I am not an expert, but work in the field of bone marrow transplant and am relatively familiar with the research in hematopoietic stem cells (capable of making bone marrow and all the red blood cells, platelets and white blood cells we need to live). I am not long or short in any stem cell associated stock.
Why are hES important in medical research, when adult stem cells have also been isolated (like the hematopoietic stem cell)? The promise they hold is pluripotency, the ability to become any type of cell, any organ, make any substance the body makes, perform any function the body can perform. They are also thought to be eternal, being such primitive cells that as they replicate and divide into millions of copies they do not deteriorate or change in nature. Imagine each cell out of millions in the stem cell line, or colony, capable of all of the wonders of growth and differentiation that the fertilized egg carries! An adult stem cell, on the other hand, has already moved a long way down the road to a specific organ or even a particular type of cell. It can also replicate and divide, keeping its primitive nature, and with the right triggers, can differentiate into cells of a particular organ or group of specialized cells. But it no longer has the pluripotency of the hES, it is already bone marrow, or liver, or nervous system.
So what does Bush’s decision mean? The first hES to be successfully isolated and grown in the lab were reported in 11/98 from two institutions. Thomson and his colleagues at the University of Wisconsin isolated hES from early human embryos (blastocysts, a stage at which the embryo has about 140 cells) and Gearhart and his colleagues at Johns Hopkins isolated hES from fetal tissue. The research was privately funded by Geron who holds rights on these hES lines with the institutions. I have not found other published reports of hES lines being established, if they exist, they have been isolated and grown in more secretive environments than universities. Bush alluded to about 60 hES lines available for federally funded reasearch; it is not clear that there are that many (Thomson, for example, clearly a leader in this field, apparently has five hES lines). Geron has publicly questioned whether there are 60 hES lines. How will scientists access hES for research? Presumably Thomson and Gearhart will be well placed to apply for federal funding; will other researchers have “equal access” to hES? (I know it’s a completely different situation, but we saw what happened when the government tried to regulate equal access for the CLECs J
Why is it a bad thing to only fund research in a few hES lines? Think about what an hES line is. For example, Thomson was able to create five hES lines in his original work. Each line came from a different blastocyst, so each has its own unique genome derived from the original sperm and egg. If I were a researcher, I could take cells from these cell lines (with payment to Geron, of course) to study what environmental factors might be needed to trigger differentiation into muscle, or neurons, or into pancreatic cells capable of producing insulin (as has been done with mouse embryonic stem cells). Once I can get them to differentiate reliably, I can expose pure samples of cells (e.g. skin cells) to different chemicals and substances to look for possible new medications. I could take cells to study the genetic sequencing and the pattern of gene activity and protein production that govern normal differentiation. I could look for abnormal genes in these cells, genes involved in diseases like breast cancer or juvenile diabetes, and study the way in which those genes are expressed as the stem cell differentiates into breast tissue or pancreas. I could study ways of getting these cells into animals suffering from a variety of disorders and diseases to explore how they might be able to repair tissues or produce the right enzyme or other substance to reverse the disorder or disease, hoping that eventually that would lead to helping humans.
What I won’t be able to do is to create any more hES lines. If something happens to an existing line, perhaps as a result of a gene it carries, there’ll be 59 available genomes instead of 60. If my research studies suggest that I should be looking at the activity of a p52 gene (associated with some breast cancers) and none of the hES lines carry that gene, I won’t be able to make a new one. What are the characteristics of the existing hES lines? How many have a Y chromosome to study? What genes do they carry for their immune systems (HLA antigens) and other systems that might prove critical down the road when we are ready to transplant them into humans, and don’t want them to be rejected?
If Bush had said no federal funding, the backlash might have run a bill through Congress with fewer restrictions. Restricted funding is better than no funding, and it’s good news for Geron, but IMHO if these restrictions stay in place it ties the hands of American researchers compared to their colleagues in Canada and Europe, and pushes research into the private sector where the ethical questions are more likely to be swept aside. |
