Slashdot Mirror
Human-Mouse Hybrids?
scientistguy writes "There is a remarkable story by Nicholas Wade in the early
morning edition of the New York Times about a discussion to create human-mouse
hybrid organisms. One of these techniques involves the introduction of genetically altered mouse embryonic stem (ES) cells (e.g. with
genes 'knocked-out' or replaced) into a developing mouse blactocyst to create progeny hybrid organisms. Typically, these progeny organisms are then bred to unaltered mice to see
if the genetic alteration has gone germline or is heritable. If heritable, mice can be bred and
animals which are homozygous for the altered gene can be phenotypically examined as long as the manipulation is not homozygous lethal or cause
sterility in a single copy state. Unless using
blastocysts from immunologically crippled mice, there would most likely be a recognition of non-self by murine immune cells not educated (which haven't seen during their development) to the human cells that would wipe them out. Nonetheless, it's amazing that it's
being contemplated due to the ethical implications of such an experiment. What if it were viable? What if there were more than just a few
human cells? Could it be sacrificed? ... or even experimented on further if part 'human'? Perhaps these
types of experiments are best relegated to little known, deserted islands far
away from the reaches of civilization (or perhaps regulation) ..."
Cheers Google ...
The nation of registry of choice for many ships is currently Liberia. Just think about it the next time you consider going on one of those delightful Disney cruises.
~Idarubicin
Don't be so afraid, the reporter got almost all his facts wrong. There will be 0 (zero) human cells in the chimera. That's not the way this procedure works. The genetic material is put in the blastocyst, and is then absorbed by some of the cells there. Those cells can then (in theory) produce the proteins that the absorbed genes code for. So the mouse's brain might have some human protiens in it, but it would still be a mouses's brain.
Also, the Bishop's comment about a few human cells per organ being acceptable: not the way it works. As I said, there will be NO human cells, and the modified cells will come in patches. As a modified cell in the blastocyte divides, all it's progeny will have the modifications, so you'll end up with an area in the adult organism that has the modifications. Is it really too much to ask that the people who are trying to make these ethical decisions put in the effort to actually learn what they're talking about before passing judgment?
I believe the reference in the news blurb is to "The Island Of Doctor Moreau" by HG Wells. :)
'He was a dreamer, a thinker, a speculative philosopher... or, as his wife would have it, an idiot.' - Douglas Adams
this was a ref to the island of dr. moreau. irv weissman could reprise the role that brando more recently played. it wasn't meant seriously.
in truth, several similar things are done, but not approaching this scale, and not anything that would have the possibility (albeit remote) of creating offspring with cells that are entirely human.
Examples ...
(1) hybrids between murine (or other rodent species) and human cells. these experiments are typically done to map genetic factors unique to one organism or assay the recessive of dominant phenotypic nature of a gene factor. In long term culture, these are unstable. Mouse and human cells have different numbers of chromosomes which are duplicated at different speeds and move toward productive mitosis (somatic cell division) at different rates. The human chromosomes lag behind in the divisions and are eventually lost over time.
(2) immunologically crippled mice grafted with parts of the human immune system to study human immune function in an 'animal model'. These mice usually bearing the SCID or RAG genetic defect don't have an adaptive response/capability to recognize foreign cells as non-self. One popular model is the SCID-hu model in which mice typically are typically injected in their kidneys with human thymus, liver, and/or lymph node tissue in a capsule. There is partial immune reconstitution in these animals by the human immune system cells and they can be used in pathogen challenge or other studies. Obviously, potential progeny offspring would not genetically inherit human cells as a chimeric organism.
(3) Human genes can be introduced into mice as transgenes or by 'knock-ins' also more properly known as gene replacements. This is done to study human gene function in an animal context often looking at the cancer causing or cancer suppressing potential of genes of interest, the developmental role of particular genes, the immunological effect of genes, and more. These changes are very often heritable and there are many genetically altered mice currently available carrying numerous different human gene products
None of the examples above are on the scale of what is being considered in creating hybrid blastocysts between mouse and human. These are obviously most likely to be viable, but a concern I have is what happens when an enterprising individual takes it to the next level and successfully does the experiment using monkey (example was Rhesus) blastocysts ...what if human neurologic tissue is grafted
into this chimeric organism? This
type of research should not be taken out to an island run by a Dr. Moreau but
really needs to carefully considered before our science moves faster than our ability to comprehend
what we have created.
They already did, didn't you know ;-)
&partner=SLASHDOT
and so did you!!!
&partner=krnlpanic
I'll have something intelligent to add one of these days...
It says:
Dipliod organisms (like all mammals including both humans and mice) have two sets of chromosomes and thus two copies of chromosome 1, two copies of chromosome 2, etc. Therefore if a particular mutation or altered gene is on, for example chromosome 3, then a mouse could have two copies of a normal chromosome (called a wild-type mouse), one normal and one altered chromosome (heterozygous), or two copies of the chromosome with the mutation (homozygous). Sometimes an animal homozygous for a certain mutation cannot survive to birth -- such a mutation is called "homozygous lethal." If the mutation is not homozygous lethal, and does not cause sterility, then one could raise a colony of mice that all have this particular mutation through selective breeding. The mice can then be examined to determine the phenotype -- or physical charactersitcs -- cause by the mutation.
and now the second sentence:
Whoever does this will have to use mice with no immune system othewise the mouse's immune system will recognise the embryonic stem cells that are introduced by the scientists as being forign and attack them. This is the same mechanism used by the body to fight off disease. (Translator's Comment: I dont think that is actualy true)
When you add the cells at the blastocyst stage, they are not absorbed; you are probably thinking of the proceedure at the ES stage, or how it's done with transgenics. This is more analagous to a knockout. The resultant animals will be chimeras; in the animal some cells will be like the host (the blastocyst) and some will be like the donor (the introduced cells). No cell will be a hybrid of the two. You can see this in the mice made for knockouts; donor cells are typically FVB's (white mice) and the hosts are C57's (black mice). The resultant animals are park C57 & part FVB. You can see it on the coat, it has black & white patches on it. (that's actually why you do it; you look for animals that have more white on them for breeding; more likely that they got the gene you altered)
There is a reason for everything. Sometimes that reason just sucks.