Biotech Takes
The brave new world of stem cells and human cloning
Steve Clark
July 2, 2008

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?

Steve Clark, Ph.D., a former professor and medical researcher at the 
University of Wisconsin School of Medicine and Public Health, is a 
free-lance writer and consultant on biotechnology issues. His blog 
BioScience Biz can be read at http://stevensclark.typepad.com/bioscience_biz

Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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