03 Jul The brave new world of stem cells and human cloning
One of the great promises of embryonic stem cell research is being able to use human cloning to derive stem cells that carry genetic defects associated with myriad maladies. These cells can be used to study the development of tissues that are affected by genetic abnormalities and used as tools for testing new therapies for intractable genetic diseases.
The way that this works is that a researcher derives an embryonic stem cell line from someone with, say Parkinson’s disease. These stem cells can be coaxed into developing into the dopamine-producing neurons that are defective in patients with the disease. Then, a number of different things can be done with these cells. For instance, the development of diseased neurons can be compared to that of normal neurons under well controlled conditions to, hopefully, yield new information on the origins and progression of the disease. Alternatively, the Parkinsonian neurons can be used to test new approaches for treating the disease.
Thus, cloning and derivation of disease-specific stem cells promises to be a powerful and novel tool for studying certain types of cardiovascular disease, certain cancers such as neuroblastoma, Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), metabolic problems such as diabetes, and so on.
Ethical concerns of cloning human embryos notwithstanding, a confounding technical problem is where will researchers find the eggs necessary for the nuclear transfer cloning procedure (the procedure used to clone Dolly, the sheep)? Obtaining human eggs is done routinely at in vitro fertilization clinics, but it does involve hormonal manipulation of young women and a somewhat invasive procedure to harvest the eggs. Who would volunteer for this just so a scientist can do lab research? How many eggs will we need to all the research scientists want to do and are there enough women donors to supply the research needs?
Researchers in England are taking a new approach to deal with the problem of egg supply. They propose to undertake nuclear transfer cloning using eggs from pigs and chromosomes from a human with the desired disease in order to create animal-human hybrid stem cells. A UK regulatory agency recently licensed a laboratory to create human-pig embryos in order to study heart disease.
In an article just published in the British newspaper, The Telegraph, a spokesman for the British Human Fertilisation and Embryology Authority said it had approved an application from the Clinical Sciences Research Institute, University of Warwick, for the creation of hybrid embryos.
The effort at the University of Warwick is led by Professor Justin St John. “This new license allows us to attempt to make human pig clones to produce embryonic stem cells,” he said.
“We will take skin cells from patients who have a mutation for certain kinds of heart disease (cardiomyopathy, which makes the heart lose its pumping strength) and put them into pig eggs after their chromosomes have been removed. We will then make embryos so that we can attempt to derive embryonic stem cells which will allow us to study some of the molecular mechanisms associated with these heart diseases.
“Ultimately they will help us to understand where some of the problems associated with these diseases arise and they could also provide models for the pharmaceutical industry to test new drugs. We will effectively be creating and studying these diseases in a dish.
“But it’s important to say that we’re at the very early stages of this research and it will take a considerable amount of time. There is still a great deal to learn about these techniques and much of our early work will involve understanding how we can make the hybrid cloning process as efficient as possible.”
The study is aimed at understanding the way the cell’s power-producing structures, called mitochondria, are passed from egg to embryo. Mitochondria contain their own small genetic program that produces many of the proteins these organelles need to power cells. In the hybrid stem cell, the mitochondria mostly come from the pig egg, and the researchers will do experiments in order to ensure that the trace of human mitochondria that are present takes over, not least because it is designed to work with human nuclear DNA.
“The key thing we are doing is trying to create stem cells without any animal mitochondria in them. So even though these hybrid embryos normally have…animal mitochondria, we are hoping to create hybrid embryo cells that would have human chromosomes as well human mitochondrial DNA.” The reason is that, as the team puts it, “mixing of these two diverse populations of mitochondria can be detrimental to cellular function.”
In fact, this is not the first British group attempting to create animal-human hybrid stem cells. Other research teams in Newcastle and London are also doing this research. The former have reportedly created hybrids with cow eggs to study genetic regulation in early development, the latter group made hybrids with a range of species to generate stem cells from people with neurodegenerative disorders. Elsewhere, Chinese researchers in Shanghai have reported success in creating human-rabbit hybrid stem cells.
Such research is not allowed in the US, at least not in federally-funded labs. But, this does not seem to stop this field from going forward, world-wide.
Does all of this represent a brave new world, or are we making a Faustian bargain?
Read more on human-animal hybrid stem cells:
- Hybrids: separating hope from the hype
- Questions answered on animal-human embryos
- Embryo research: a source of hope or horror?
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