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Typhon's children

  
 
jentacular dreams
10:02 / 08.11.06
Following on from this and this

Human-bovine chimarae for use in stem cell research. The current plans would not allow the resulting zygote (assuming one is viable) to develop for more than a few days, but I still find myself unnerved.

The bovine-human hybrid wouldn't be the first human chimera but it would still be 100% human from a nuclear standpoint. Is this any different to simply working on human fetuses? If not, I think I like it even less as it seems like a long way to go to (attempt to) dress up the experiments as something other than what they are. And once this line is crossed, once it becomes acceptable, how long before such a chimera is brought to term. A baby with - best case scenario - the mitochondria of a cow (the worst case scenario isn't worth contemplating). Is there any moral difference between this and cloning for research purposes? And is there really any greater scientific benefit than cloning experiments would produce? Is it just me or is there an element of "guess what hasn't been tried yet" coupled with a slightly worrying "it's not really human so no-one will complain" spin to this? And if the latter succeeds, how far can society let it proceed?
 
 
Evil Scientist
13:42 / 08.11.06
Is this any different to simply working on human fetuses?

In short, yes it is. The foetus is not considered to have developed until the eighth week of pregnancy. There is a very big difference between that and the cluster of cells that will be created and then disposed of by the fifth day of development.

And once this line is crossed, once it becomes acceptable, how long before such a chimera is brought to term?

Well, this is an attempt to create an alternative source of stem cells for research rather than a development in reproductive technology. Nothing I have read on this so far suggests that anyone believes there would be any benefit to bringing such an organism to term (even if it was viable to do so).

Is there any moral difference between this and cloning for research purposes?

I would say so yes. Cloning for research purposes in this case creates and uses viable clusters of human cells. Most people involved in the area seem to agree that use of nuclear transfer technology (to give it its proper name) to produce humans as a method of reproduction is, at best, extremely impractical.

Is it just me or is there an element of "guess what hasn't been tried yet" coupled with a slightly worrying "it's not really human so no-one will complain" spin to this?

Well considering anything involving "potential baby" cells and scientists tends to get whipped up into a media panic pretty quickly I have a feeling they didn't do this thinking they wouldn't get any kind of opposition/criticism.

Also, it's unlikely to be a matter of them trying it for no real reason other than it hasn't been done. There would most probably be a certain amount of theoretical research to support it before it went into practical research.
 
 
jentacular dreams
15:15 / 08.11.06
"Is this any different to simply working on human fetuses?"

In short, yes it is. The foetus is not considered to have developed until the eighth week of pregnancy. There is a very big difference between that and the cluster of cells that will be created and then disposed of by the fifth day of development.

Perhaps I should have used 'blastocyst', but the scientific question surely still stands? I'm not convinced that utilising a bovine zygote as the recipient of NTT as a source of stem cells is all that different to normal blastocystine stem cell research. It just seems a strange branch to head off on.

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

Given that mitochondrial dysfunction is pretty close to the heart of both conditions (along with a host of other neurodegenerative disorders), is removing human mitochondria from the equation actually going to give much insight into the mechanism of the diseases? The majority of these conditions do not manifest until well into maturity, so is it not unlikely that a stem cell will exhibit the relevant symptoms within the window allowed for? I'm also less than convinced that the stem cells will operate normally unless something in the process reverses telomere breakdown.

If it's going to be done, why not just use a human ova? Of course there's no current plans to bring such organisms to term, but it strikes me that this is the start of something that could end very badly. Currently we use human genes in animal models. How long before we're doing the reverse - popping 'animal' genes into a human genome (or even just shuffling chromosomes), then shunting that nucleus into a bovine cell? It's generally agreed that good animal models are hard to find, so I fear it's only a matter of time until someone takes a human model and makes it just animal enough so that the law's not quite so stringent.
 
 
Evil Scientist
09:30 / 09.11.06
Given that mitochondrial dysfunction is pretty close to the heart of both conditions (along with a host of other neurodegenerative disorders), is removing human mitochondria from the equation actually going to give much insight into the mechanism of the diseases?

Are you sure about that? As far as I am aware Alzheimer's is caused by the build-up of plaques of malformed amyloid beta protein in the brain. Parkinson's is caused by the loss of dopamine secreting cells (and subsequent melanin loss). I haven't found anything in my quick hunt around on the subject that suggests mitochondrial dysfunction is at the heart of either problem.

From the second article:

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.

Unfortunately they don't describe this very well, but to clarify; they aren't saying that the mitochondria of the cell will be 100% of bovine origin. What they are saying is that there will still be a small percentage of bovine mitochondria present in the new cell. It will, however, have an overwhelming majority of human-origin mitochondria present.

Perhaps I should have used 'blastocyst', but the scientific question surely still stands?

Well, a blastocyst is still very different to an embryo. It's more differentiated than what you have in the first five days of development, but arguably (obviously depending on your stance on this) still little more than a cluster of cells.

If we modify your original question to "Is this any different to working on human blastocysts?" then the answer is still yes.

If it's going to be done, why not just use a human ova? Of course there's no current plans to bring such organisms to term, but it strikes me that this is the start of something that could end very badly.

There's certainly an "ethical" factor being taken into account here that by creating a chimerical cell they are getting around the rather controversial subject of having to use truely human pre-foetal cell masses in their research.

But you do need to separate the two fields of somatic nuclear transfer technology and it's sister science of reproductive cloning. There is no intention to even attempt to bring these cells to term. Your argument that this could be the start of a slippery slope towards us implanting animal genes is one that should most certainly be considered. But you seem to be ignoring the fact that this area of research is not being given free range to create whatever they want. It's heavily regulated.

Now you could counter with the argument that all it will take is for one "mad" scientist to go and do a Doctor Moreau in some third world dictatorship. But this is an argument that can be applied to practically any technology. Which is where international law, etc, comes into play.
 
 
jentacular dreams
12:39 / 09.11.06
Really, I though the point of NTT was nuclear transfer, where do the human mitochondria come from? I should probably look up the original article really.

As for the mitochondrial dysfunction thing, it's fairly well reported. Try this and this. There's plenty of articles and reviews on pubmed, but linking into their search engine is beyond my abilities.

The second article I linked to in my original post talks to an extent about the lack of regulation for such experiments, especially if the line between human and animal is less clear cut. And I know from firsthand experience how easy it is to carry on with experiments because they seem interesting without giving full thought to the ethical implications. I just question the experiment's neccessity and validity, and worry that, yes, it might lay the groundwork for some potentially very unethical work. I don't hold with the one mad scientist viewpoint. No-one can do any serious work on their own (not something that major anyway). But such regulations are rarely international.
 
 
Evil Scientist
08:32 / 10.11.06
The pubmed stuff seems to be mainly abstracts as far as I can access. But here is a line from one of them which seems to be mentioned in on form or another in most.

The pathogenesis of Parkinson's disease (PD) remains obscure, but there is increasing evidence that impairment of mitochondrial function, oxidative damage, and inflammation are contributing factors.

"Contibuting factor" are the words that I want to focus on here. You're not wrong that mitochondrial dysfunction is one of the causative agents of these conditions (and thanks for the links, it's always nice to learn something new). However, it is inaccurate to say that it is at the heart of the condition. There are other factors which contribute to the development of these diseases.

One factor is that of genetics. It has been established that there are inheritable genetic factors which make one more likely to develop these conditions.

Earlier you asked how this particular technique could be used to study Alzheimers as it is a condition which generally presents later in life.

From the wiki on Somatic cell nuclear transfer technology:

A potential use of genetically-customized stem cells would be to create cell lines that have any genes linked to a particular disease. For example, if a person with Parkinson's disease donated his or her somatic cells, then the stem cells resulting SCNT would have any genes which contribute to Parkinson's disease. In this scenario, the disease-specific stem cell lines would be studied in order to better understand the disease.

This abstract was taken from Pubmed by following the link sited by that sentance.

Human embryonic stem cells: origin, properties and applications.

Semb H.

Stem Cell Center, Lund University, Lund, Sweden. henrik.semb@med.lu.se

Human embryonic stem cells originate from the human preimplantation embryo. The derivation of the first human embryonic stem cells was reported in 1998. Since then we have learnt a great deal about how to isolate and culture these cells. Additionally, their stem cell phenotype and differentiation competence have been determined. Although it is expected that many basic biological properties, such as self-renewal and cell specification, are evolutionary conserved, at least from the mouse, we lack significant knowledge about the molecular events that regulate the unique stem cell features of human embryonic stem cells. The pluripotent nature of human embryonic stem cells has attracted great interest in using them as a source of cells and tissues in cell therapy. Recent progress in human somatic cell nuclear transfer suggests that there may be a solution to the immunotolerance problems associated with the use of human embryonic stem cells in cell-replacement therapy. Thus, human embryonic stem cells supply the research community with unique research tools to study basic biological processes in human cells, model human genetic diseases and develop new cell-replacement therapies.

In this particular branch of Alzheimer's research the origin of the mitochondria in the cells is irrelevant, because that isn't what is being investigated here.

I understand your concerns regarding the legal and ethical questions surrounding the concept of creating human/animal chimeras even at a purely cellular level. But I think that as long as we are vigilant and ensure that we don't try to, for instance, use this as the foothold to breed a race of "lab humans" for testing purposes then this is an acceptable level of development.
 
 
Hydra vs Leviathan
10:44 / 10.11.06
So, if your default ethical position is that embryos/fetuses/whatever aren't human and don't have any rights until they're capable of survival outside the womb, is there any way in which this is either ethically or pragmatically superior to simply using human ova/blastocysts/whatever?

IMO the strongest argument against the use of non-human animals in any kind of medical [as opposed to species-specific veterinary] research is that it has been documented many, many times that drugs that work on or are harmless to one species can very easily not work on or be highly toxic to another (Thalidomide was harmless to guinea pigs IIRC, that drug that nearly killed the volunteers in that recent UK drug trial scandal had been tested on rats and monkeys, hell, chocolate is poisonous to dogs, and loads of animals can eat wild berries, fungi etc that could kill us...) Whether that would be true of mostly human cells, i don't know, but it would still seem far more sensible, if there's a choice between mostly human and completely human, to use the completely human option - after all, it won't be human/cow chimeras (unless there's some secret plan for mass breeding of a partially bovine slave race) that these therapies will eventually be used on...
 
 
Evil Scientist
12:45 / 10.11.06
So, if your default ethical position is that embryos/fetuses/whatever aren't human and don't have any rights until they're capable of survival outside the womb, is there any way in which this is either ethically or pragmatically superior to simply using human ova/blastocysts/whatever?

I guess it depends on whether that is your default ethical position or not doesn't it? It isn't exactly mine.

My personal preference would be to use human cellular material rather than chimerical cells, in part for the reasons you mention Natty. I don't personally consider blastocysts or ova to be anything other than human tissue, and don't think that human rights should be extended to protect them. Others feel differently however, and so we have come to the point where researchers are having to use the next best thing for their studies.

IMO the strongest argument against the use of non-human animals in any kind of medical [as opposed to species-specific veterinary] research is that it has been documented many, many times that drugs that work on or are harmless to one species can very easily not work on or be highly toxic to another (Thalidomide was harmless to guinea pigs IIRC, that drug that nearly killed the volunteers in that recent UK drug trial scandal had been tested on rats and monkeys, hell, chocolate is poisonous to dogs, and loads of animals can eat wild berries, fungi etc that could kill us...)

Of course there are many many more examples of drugs used commonly today that were tested on animals that work in exactly the same way in humans as they do in animals. I think it's inaccurate to hold up three (arguably four) examples of drug testing as a reason why the entire system is flawed. But we can discuss that over on one of the animal testing threads if you like.

Your argument here could be seen as a very good reason why we need to genetically modify animals to be more similar to humans so that we can more effectively model drug effects on them. There would be risks to creating transgenic creatures such as we could easily be creating a bridge for animal diseases to jump across into human hosts.

However in this case that isn't really a risk. The cells need to be kept in a sterile environment in order to be studied. They are to be used as a tool of analysis. They are not intended to be used to create chimerical humans (SNTT is not really the best reproductive technology anyway, its massively ineffecient, uneconomical, and potentially dangerous to any infants created this way).
 
  
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