Author: Kerry Silva McPherson
Does every scientist have that one field of science that you don’t study, but for some inexplicable reason you’re obsessed with it? I’m married to the cancer biology research field, my sidepiece is stem cell research. I love the biology and all the drama (policy) that goes with it. I’m nowhere near an expert, I’ve briefly handled adult stem cells in the lab once or twice. But that doesn’t mean I can’t read and read and read... and write about it.
Before we get into the narrative I’d like to share today, here are some stem cell basics:
What are stem cells?
Any cell with two properties:
Why do we research them?
What kinds of stem cells are there?
To discuss stem cell research without including science policy is a disservice to the history of the field. Stem cells and science policy are inherently intertwined. Displaying a love/hate, push/pull relationship, policy restricts research, causing scientists to innovate. On the other hand, scientists advocate and educate, causing change in policy.
Stem cell research during the Bush Administration
The first embryonic stem cell (ESC) line was made in 1998 from spare IVF embryos, a marvelous feat which “provide[s] a potentially limitless source of cells for drug discovery and transplantation therapies.” Public response to ESC research was quick, in part due to religious advocacy. In 2001, George W. Bush placed a ban of federal funds for research on any newly created embryonic cell lines. Unfortunately, most eligible lines were derived from Caucasian lineage, leading to racial bias in stem cell research. Furthermore, these lines were cultured using nascent techniques and lacked the quality necessary for regenerative medicine treatment.
As I said before, stem cell scientists are innovative. They had restrictions on their ability to perform ESC research, so they made embryonic-like stem cells. In 2006 the first adult mouse cells were de-differentiated into embryonic-like stem cells by Japanese researchers, leading to numerous research groups reporting the methodology on how to revert human cells to a stem cell state in 2007. The reprogrammed cells, induced pluripotent stem cells (iPSCs), exhibited stem cell-like morphology, expressed stem cell protein markers, and were capable of differentiating into cells of all three germ layers. iPSCs, in my humble opinion, is one of the coolest accomplishments in cell biology history. Converting adult cells into stem cells is Harry Potter-like transfiguration class stuff, but it’s not magic, it’s science!
iPSC and ASC research flourished during Bush’s administration. And scientists did some pretty impressive stuff with these cells. iPSCs are used for patient-specific cell models to study pathogenesis and drug discovery of diseases like Parkinson’s, autism, and heart disease. iPSCs are also potential therapeutics to rebuild tissues with limited risk of an immune response. Amidst the success of iPSC research there is concern about iPSCs’ limitations. iPSCs are not true ESCs and unwanted artifacts of the cell’s origin likely persist. Also, iPSCs take a long time to differentiate with a low success rate. Clearly, there is still a need for ESC research.
President Barack Obama's Executive order
The Bush stem cell restriction era was halted on March 9, 2009, when President Barack Obama issued an executive order allowing federal funding of embryonic stem cell research on new embryonic stem cells lines. This order was welcomed by Americans at a 60% approval rate (props to stem cell advocates and Michael J. Fox). But the ethical controversy did not die there.
Obama’s executive order was interpreted by some to violate the Dicky – Wicker Amendment, a 1995 law that restricts “research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero.” In 2010, ASC scientists, Dr. James Sherley and Dr. Theresa Deisher sued the NIH for allocating funds to ESC research in violation of Dicky – Wicker. Although possible that Sherly and Deisher’s motivation to sue were their pro-life beliefs, it should not be ignored that Sherly and Deisher competed for funding with ESC researchers. Sherly and Desher ultimately lost. Obama’s executive order was upheld and the Sherley vs Sebelius appeal was rejected by the supreme court.
The 14-day Rule
Even with Obama’s executive order, ESC research is restricted by a 14-day policy where ESCs cannot be cultured for longer than 14 days in vitro. The 14-day rule is ubiquitous in most countries that conduct ESC research. For some time, the 14-day rule wasn’t much of a limitation, mainly because scientists could not sustain embryonic development in vitro for long. The embryo implants itself to the uterine wall on day 7, and until 2016 scientists could not cross the 7-day threshold. Recent advancements enable scientists to now culture embryos for two weeks in vitro. Researchers currently conducting embryonic research must halt their experiment at 14 days, not because the embryos aren’t viable but because of the 14-day policy.
Once again, researchers are facing a restriction impeding their research, and thus, they must innovate. Since scientists cannot use human embryos in vitro past 14 days, they have started making synthetic embryos from ES cell lines. Researchers at the University of Michigan are using microfluidics to culture embryonic-like structures in vitro and have successfully passed the threshold of the formation of the primitive streak, the hallmark event of gastrulation (production of three germ layers). The primary investigator of the study, Jianping Fu, claims the embryonic-like structures should be less controversial than using IVF embryos for research. They can be used to study embryo development, improve IVF methods, and test pharmaceutical toxicity to embryos.
Perhaps Fu is overly optimistic about the public’s opinion on synthetic embryos. In addition to destroying embryos, pro-life advocates are ardently against the creation of life. Fu argues that these synthetic embryos will not and cannot develop into a human being, and therefore should not be privy to the 14-day rule.
The NIH has not made any restrictions against synthetic embryo research, and as of now, it remains ambiguous as to whether or not synthetic embryos will be regulated similar to human embryo research. It seems once again that stem cell research policy needs to be revisited. But in which direction? More or fewer restrictions?
Regardless of which side of the stem cell debate you lean towards, it is necessary to consider public opinion. In a current climate where public trust of doctors and science is falling, we must advocate for policy that does not give the public further feelings of mistrust. The policy set into place should somewhat reflect the beliefs of the tax-payers who fund our research. If you are a scientist who passionately believes in the advancement of stem cell research, please participate in science education and science communications and advocate for your cause.