Of mice and men

Rebecca Morelle
Health reporter, BBC News

UK scientists are seeking permission to place human nuclei into animal eggs in a bid to create stem cell lines.

Why do researchers believe the intermingling of species could be vital to science?

The latest application is to create stem cells

The mixing up and merging of species is not new to science: a multitude of creatures straddling the line between animal and human already exist in laboratories around the world.

But far from seeing their role as creators of freak-show fodder, scientists believe the creation of part-human part-animal creatures can help to study disease, advance areas such as fertility, and boost understanding of our basic biology.

These creatures are called chimeras, and are defined as organisms that contain at least two genetically different groups of cells originating from different organisms.

Different from hybrids, which are formed when one species' egg is fertilised with another species' sperm, such as the horse-donkey-cross mule, chimeras can occur between the same species or between different species; exist in nature or be created in the laboratory.

Although fairly rare, chimeras made of two humans do exist, most commonly formed when non-identical twins fuse in the womb to create a single person.

If a male embryo fuses with a female embryo, this can result in hermaphroditism, where a person has a mixture of male and female sexual organs. But, if the embryos are of the same sex, then there may be no obvious differences apparent at all.

Sheep + Goat = Geep

However, it is the chimeras made from different species that are currently proving of most interest to scientists.

The creation of the oddly named Geep in 1984, a creature formed by merging the embryos of a sheep and goat, opened the floodgates into an unprecedented area of research.

The "Geep" opened the floodgates into chimera research

And these interspecies chimeras can be created in a variety of ways.

In the proposed stem cell research, although the animal egg has been emptied of its nuclei, tiny amounts of mitochondrial DNA would mix with the human nuclei and the resulting stems cells would be about 99.9% human and 0.1% animal - on the cusp of being chimeric.

Other methods for creating chimeras include:

• Fusing embryos of different species together;
• Transplanted genes, cells, tissues or organs from one species into another;
• Or injecting stem cells from one species into a developing embryo or an adult of another species.

Scientists say these interspecies creatures could help science in a number of ways - from making human stem cells and improving animal models to study disease, to one day, perhaps, creating organ or tissue factories for transplants into humans.

And using chimeras also helps scientists to carry out experiments, such as those using developing embryos, which would be ethically difficult to perform on human beings.

Grafting tissue

On the application for proposed human-cow stem cell study, Dr Stephen Minger, of King's College London, said: "What we are proposing to do is not really create chimeras but rather use non-human oocytes (egg cells) merely as a surrogate to generate human embryonic stem cell lines from individuals with genetic forms of neurodegenerative diseases."

The group plans to use the disease-specific stem cells to study conditions such Alzheimer's or Parkinson's.

Other chimera research is also underway where scientists are merging species to create better animal models to study disease.

One group is working on sperm production

In Boston, US, scientists have transplanted human breast tissue onto mice to study the development of breast cancer.

While another American team recently showed it was able to grow immature human testicular tissue in mice. The researchers wanted to see if it would be possible to harvest sperm, for example from boys who had contracted cancer in childhood, from this tissue which could then be frozen and stored for later use.

And whole organ research is also underway: researchers have shown that it is possible to create a mouse with 95% of human liver cells, and other teams have created a mouse with a human immune system - both groups hope they can use the animal-human models to better understand the origins of disease.

One of the latest chimeras to hit the headlines was created by scientists in Korea. They sparked controversy when they injected human embryonic stem cells into developing mouse embryos.

The finding that these the cells were then distributed throughout the mouse's body, including the brain, caused public outrage, and the scientists later abandoned the experiments as the protests increased.

But as ethically difficult as this research seems, these scientists said they believed it could add a great deal to our knowledge of how embryos develop.

The creation of chimeras forces us to reconsider just what it really means to be human, and the answer to this is not clear cut.

Loopholes

The lack of a clear answer is posing problems in regulating this fast-moving area of science.

In the UK, all experiments concerning the use of human embryos are currently regulated under the Human Fertilisation and Embryology Act which came into force in 1990.

And while the proposed UK research to create stem cells by mixing human with cow probably falls under this jurisdiction because the stem cells will be 99.9% human, in other cases, where the human-animal boundary is more blurred, it is not as straightforward.

We've agreed as a community that we do not believe these experiments are necessary, so we have agreed not to do them Dr Stephen Minger Send us your views

Dr Minger said: "For other chimeras, there is a regulatory void and there are no guidelines that dictate what can happen one way or the other."

He said in the UK, the scientist community had introduced a self-imposed ban to stop experiments where human stem cells were injected into developing embryos of another species.

"We've agreed as a community that we do not believe these experiments are necessary, so we have agreed not to do them."

He said it would be useful to have additional regulation to this research.

"If it would make the public feel more secure for us to have chimeric regulations, then I'm alright with that.

"What is important is that we have a system whereby we can have an informed debate about this and then make a decision that is consensual."