By Ricki Lewis
Palm Springs Ive been hearing about stem cells at scientific meetings for nearly a decade from the yearly International Society for Stem Cell Research meetings, to stem cell symposia at various large conferences, to focused events such as the New York Stem Cell Foundation meetings. But it is a poster at a meeting here in Palm Springs that really has excited me.
Im at the annual meeting of the CHDI Foundation, which funds research to discover treatments for Huntington disease. This cruel illness begins in men and women in their prime, causing uncontrollable movements and sometimes cognitive decline. With the ruthless pattern of autosomal dominant inheritance, children watch affected parents and other older relatives slowly lose control, knowing that this may be their own, or their childrens, future. Genetic testing can identify pre-manifest individuals who have inherited the mutation, and there is no cure despite the House episode in which a patient jerks and the snarky doc barks, Order a genetic test! Start the Huntingtons meds!
The poster Im drawn to is on a square of neat white fabric in the corner of the exhibition room. It lacks the complex biochemical pathways and clever experiments of the other posters, but instead quietly describes the potential of stem cell research with this one powerful example Huntington disease.
The author, Tomas Stojanov, PhD, explains how Sydney IVF has obtained human embryonic stem cells that have the Huntingtons mutation from extra embryos that couples undergoing IVF have donated. The human research ethics committee of the National Health and Medical Research Council approved the culturing of the embryos for legally defined embryos that are excess to the couples reproductive needs or intentions. The decision did not affect their treatment, they werent paid, and their private information and identity were kept confidential.
Obtaining hES cells requires in vitro fertilization (IVF) followed by pre-implantation genetic diagnosis (PGD), which tests a cell of an 8-celled embryo for a familys mutation. If it isnt there, the remaining 7-celled embryo can be implanted in the woman. If not, it can be discarded or studied. Nurturing it into an embryo is technically not possible and ethically too disturbing, evoking images of the pickled fetuses in Brave New World. But letting development go far enough to collect inner cell mass cells, which can then be cultured to yield ES cells, can be a tremendous boon to basic research. That is actually the goal of most hES cell research, not the therapeutic applications that the media and politicians trumpet.
These HD hES cells, which will be available to researchers in a few months, will make it possible to chronicle the earliest hints of the disease by supplying cocktails of the appropriate growth factors to steer specialization towards neural progenitors and, ultimately, the neurons that accumulate intractable tracts of the amino acid glutamine in the disease. Global gene expression profiling can reveal effects on all other genes, painting portraits of the pathology that have never before been seen, which hopefully will reveal new drug targets. Most exciting is the coming use of inducible genetic controls that enable researchers to activate the mutant gene at any time, so that what is growing in cell culture can mimic what is happening in a person in the decades before those first telltale movements begin.
The HD hES cells promise a degree of mimicry that is not possible with the much-promoted induced pluripotent stem cells. Read the papers on the iPS cells and youll find qualifiers galore essentially identical to ES cells; almost identical, behave like, and similar to. Dumping four biochemical factors onto skin fibroblasts is simply not the same as starting from scratch to watch a disease develop in tissue culture.
What researchers find from the Sydney hES HD cells, and from similar efforts at a handful of universities, will complement ongoing studies to catalog the earliest signs of HD the unusual eye movements, changes in gait, and even altered facial expression that some clinicians say reveal who has inherited the family legacy.
Thousands of families worldwide are living with Huntington disease. A few hundred early embryos not fetuses, not babies stuffed into test tubes as President Bush imagines, but the deceptively unremarkable inner cell mass cells that become ES cells can illuminate the disease process in a way never before seen. Multiply that by the many other diseases whose underpinnings we do not understand, and it is clear that it is unethical to not allow this research. Wheres the controversy?
Ricki Lewis is a fellow at the Alden March Bioethics Institute and a geneticist. She has just published Stem Cell Symphony, a novel about HD, stem cells, iPods, and U2. Check it out on amazon.com.