Archive for the ‘Embryonic Stem Cells’ Category

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Keeping the brain plastic

Wednesday, 31 March, 2010

Neural plasticity, the capacity for neurons to change their connections, is a fundamental property of the brain. It’s what allows us to learn. But as we age, the plasticity of the brain decreases. Indeed, there are developmental windows called ‘critical periods’ where the brain is especially plastic, usually when very young. The neural basis for vision, as an example, is laid down at during infancy, and doesn’t change easily thereafter. This is why kittens, raised in a visual environment of many vertical stripes, find it difficult as adult cats to see horizontal stripes – their brains, while plastic, had adapted for certain visual features, and found it difficult to adapt to new ones.

Recently, researchers at the University of California San Francisco have found a way to renew the infant-like plasticity of the mouse brain, allowing childlike learning to begin again. They did this by injecting embryonic mouse neurons (not to be confused with embryonic stem cells) into young mice, which had been raised with one eye deprived of light. Without the injection, mice that were deprived up until around a month old (the usual critical period for mouse ocular dominance) would have difficulty adapting to seeing through the eye that had been deprived of light. But with an injection of embryonic neurons into the brain, the mice went through sort of a second critical period, when the injected brain cells were about a month old, thereby aiding the mice to learn to see from their deprived eye.

This has profound consequences for enhancement of human intelligence. The obvious therapeutic outcome would be using embryonic human neurons, taken from human embryos or cultured from human embryonic stem cells, and injecting these into adult humans to give a second chance at a critical period of learning, which would be useful for re-learning to walk after an injury or learning to adapt to blindness (or, I don’t know…learning to control your new cyborg limbs?). But on a grander scale, if we could have a constant trickle of neural stem cells, developing into immature neurons, throughout life, we could very well keep our critical periods going for the rest of our lives, allowing our brains to stay young and malleable!

There is one caveat I can think of. There must be a reason why the brain has evolved to shut off critical periods of learning. Most likely, learning is a costly process in some way, thereby creating a pressure to keep learning periods are short as possible.  If this is merely an increased energy cost, humans in the first world can probably deal with it (seeing as most of us eat too much food energy anyway). But if shutting down mechanisms of learning is necessary for enhancing the function of the newly learned circuits (that is, if we don’t perform as well if we keep ‘changing our minds’), there may be a question of whether learning is worth the cost.

I would assume in this ever changing technological environment and with our lives getting longer and longer (making what we learned during our critical period more and more irrelevant), that keeping the brain plastic would be very useful indeed.

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NIH-funded embryonic stem cell research is now ALMOST legal

Tuesday, 10 March, 2009

I really, really don’t want to rain on anyone’s parade, but you still can’t get federal funding for embryonic stem cell research in the US. But with President Obama signing an executive order yesterday (my time) overturning President Bush’s 2001 statement that banned federal funding for embryo-destructive research, it is one step closer.

It would be good, however, to remember that the ban on federal funding for such research did not orginate with President Bush. The Dickey-Wicker Amendment, which was enacted by Congress in 1996 (during Clinton’s years) and renewed every year since. This law prohibits the US Health and Human Services (of with the National Insitute of Heatlh is a part) from using funding for

(1) the creation of a human embryo or embryos for research purposes; or
(2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death

So Obama himself hasn’t pulled down all the barriers, contrary to most uninformed media reports (The New York Times gets it right, though it is a bit unfair on Obama. And scientific journals like Nature, of course, get this right as well). In addition, Obama has not said anything expressly approving federal funding for embryonic stem cell research, so the matter is far from settled legally.

But don’t despair just yet. The removal of the Bush ban on funding this research, and the fact that Obama is supportive of such research, means that when new legislation does appear to permit such funding, President Obama will likely not veto the changes like Bush did (twice).

An important battle has been won, but the war is not over yet. I wouldn’t be celebrating freedom of research just yet.

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Foetal stem cells cause tumours: Irrelevant and obvious

Friday, 20 February, 2009

Too many people overreacting about a recently released story of a boy developing tumours subsequent to being treated by foetal stem cells, grasping onto the case as evidence for the soundness of their moral viewpoint on embryonic stem cells. A typical example is Josephine Quintavalle of Comment on Reproductive Ethics, who is reported to have said:

The risks of tumour formation in association with embryonic stem cells are widely acknowledged and one reason why there are very serious concerns about the proposed use of such cells in treating spinal cord injury in the US. It would appear from this report that foetal stem cells are similarly unstable. These are not areas of therapy we should be rushing into, whatever the ethical debates surrounding the use of embryo or foetal tissue per se.

Notice she just assumed foetal stem cells are the same as embryonic stem cells?

The first objection to this madness is simply that embryos are not foetuses and foetuses are not embryos. The paper in which this case was presented, in the journal PLoS Medicine, clearly states that the “neural stem cells used were derived from fetuses aborted at week 8-12”, and in fact defines the term fetus as “unborn offspring from the end of the 8th week after conception”.  These are not pluripotent embryonic stem cells, sourced from embryos and able to develop into many tissues. The cells used were ‘merely’ multipotent foetal neural stem cells, sourced from foetuses and only able to develop into neural tissues.

Pro-life groups, who rely on misusing words to equivocate babies with single-celled zygotes, are likely to continue making this mistake. Strangest of all, they should not be opposed to foetal stem cells, as they are sourced from abortions that would have happened anyway. In this sense, they are similar to the embryonic stem cells sourced from otherwise discarded leftover IVF embryos. Better they be used as a cure rather than be binned and incinerated, right? So, this case, while unfortunate, is irrelevant to whether embryonic stem cells should be used.

Secondly, cancer is a risk present with all stem cells (and indeed all cells). After all, stem cells are, by definition, able to proliferate – to grow and mitotically divide – many times. As a consequence, it only takes a single mutation to some aspect of growth regulation for a stem cell to become a tumour. For a normal cell to become cancerous, it must gain the ability to proliferate in addition to a lack of regulation. This has been known for ages, and is reviewed well by Michael Clarke and Michael Becker in Scientific American and, more technically, by Michael Clarke and Margeret Fuller in the journal Cell. All stem cells pose a risk of turning cancerous, regardless of whether they are adult stem cells, embryonic stem cells, or a somatic cell induced into pluripotency.

Embryonic stem cells, foetal stem cells and induced pluripotent stem cells carry such high risk of cancer for the same reason that makes them have such great potential for repairing tissue and curing disease. While adult stem cells can divide many times, only embryonic stem cells (or similar) can divide almost indefinitely.The restricted lifespan of adult stem cells make them less likely to form a tumour, but also means they have less time to repair the tissue. Preferring stem cells for this reason is rather like preferring to hire elderly people to be spies because they likely to retire or die before they go rogue or are turned into being a double agent.

Unfortunately, all current stem cell therapies with the promise of embryonic stem cells also carry the elevated risk of cancer.  So this case of a boy developing tumours from stem cell therapy, while unfortunate, was obviously going to happen to someone.

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Mice reject human embryonic cells – so what?

Friday, 22 August, 2008

Researchers at Stanford University School of Medicine found that mice mounted an immune response after being injected with human embryonic stem cells (hESCs). The result: all the transplanted stem cells—which hold the promise of maturing into several different types of tissue—were dead within a week [from Scientific American].

All of this is leading many to claim that embryonic stem cells won’t work. But that is is big stretch from the data in that study.

First, this study examined human cells implanted into mice. Mice are not the same as humans. The genetic difference there is obviously going to be a factor. That said, it is true that mice have also rejected murine embryonic stem cells (Wu et al 2008), but some research has shown that mice are more likely to develop a tolerance to embryonic cells than to other transplanted tissues (Robertson et al 2007).

Second, scientists already thought this would happen. It is for that reason that the whole concept of therapeutic cloning was considered. If the embryonic cells were genetically identical to the patient, the immune system would likely not attack those cells.

That said, therapeutic cloning still leaves the 16 genes that are present in the egg donor’s mitochondria. It is possible (though, considering that these genes are not cell-surface proteins, unlikely) that this slight difference could still cause an immune response. This has lead some to tout induced pluripotent stem cells as an answer, but those cells are genetically modified in order to induce their pluripotency, so not even they are identical.

I think that both therapeutic cloning and induced pluripotency will be solutions to this immune problem, although I personally would favour the genetic modification of the immune system to stop it being so reckless and killing that which is trying to help. After all, those of us who suffer from autoimmune diseases know that the immune system can quite easily attack cells which are genetically identical to all your other cells.

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Even if an embryo is a full person, can embryo destruction still be ok?

Saturday, 26 July, 2008

The title of this work asks a difficult question for anyone to answer in a way that reflects their full view. It is easy to respond flippantly, saying “No, killing is always wrong, no matter the good that could come of it” or “The ends justify the means”. But from experience, I know these answers do not always reflect the view taken outside of the ‘status of the embryo’ debate. So, if we do accept that an embryo deserves all human rights, does that mean that no treatment or cures to come of it are justifiable? I wish to take you through an embryonic stem cell research scenario, and then a few other scenarios which I will argue are ethically similar to judge responses. Finally, I will look at one scenario – that of normal human procreation – to see if it is similar.

In a future embryonic stem cell therapy, a human embryo – around four or five days after it was just a single cell – is harvested for stem cells. The inner cell mass (also known as an embryoblast) is a group of a few dozen cells that could give rise to any human body cell, except perhaps the placenta. Therefore, these cells could be taken out of the embryo and, instead of growing into a human child, could be multiplied endlessly in the lab, and then eventually turned into many human kidneys, human hearts and even human brain cells. But to get these replacement organs, which could be used to save lives of people who may never otherwise receive an organ, and replacement cells, which could prevent the need for organ replacement altogether by repairing the organ while it remains in the body, a human embryo must be sacrificed. So, that entails destroying a life in order to save many other lives.

Thought experiments A – Transplants and Terrorists

To examine the ethical problems that this may create, let us consider a thought experiment. This is Thomson’s transplant case:

A brilliant transplant surgeon has five patients, each in need of a different organ, each of whom will die without that organ. Unfortunately, there are no organs available to perform any of these five transplant operations. A healthy young traveler, just passing through the city the doctor works in, comes in for a routine checkup. In the course of doing the checkup, the doctor discovers that his organs are compatible with all five of his dying patients. Suppose further that if the young man were to disappear, no one would suspect the doctor.

Now, I’m fairly sure that most people would say it is not acceptable for the doctor to kill the man. And it is because the pro-life camp see each human embryo as a little person, not morally different to the traveler in the above example, that they object to embryo-destructive yet life-saving research.

Let’s look at another, this time real, incident. This one is used by John Harris, in his recent work Enhancing Evolution, in the chapter titled ‘The Irredeemable Paradox of the Embryo’ (p117-8)

On September 11, 2001, passengers on flight “United 93” are reliably believed to have overcome hijackers and forced a hijacked plane to crash into a field in Pennsylvania, so forestalling the attempt to target a highly populated and high profile building, but killing everyone on board. Such an act, while defending the victims in the “target of choice” did involve killing the innocent passengers and crew.

Harris then goes on to consider the moral implications of this, and concluded that there is an inconsistency present for those who are pro-life in the embryo debate but also approve of the actions undertaken on United 93. While it is true that the innocent would have died anyway, so too does everyone at one stage; murder is no less wrong because of the inevitability of death. The unwilling transplant donor will also have died anyway, though it may have taken several decades. So why is it that we can’t kill a person in order to save lives, but the actions of a few passengers on United 93 are rewarded for killing to save lives?

Thought experiments B – Trolleys and more Trolleys

I suspect that to find the answer, one must look at a few thought experiments known to ethicists as ‘trolley problems’. The classic trolley problem is the ‘Bystander problem’, which goes like this:

A trolley (i.e. tram/train) is running out of control down a track. In its path are 5 people who have been tied to the track by a mad philosopher. Fortunately, you can flip a switch which will lead the trolley down a side track to safety. Unfortunately, there is a single bystander on that side track. Should you flip the switch?

Generally, most people say that they would flip the switch – saving the five but killing the bystander (although some would say that this would make you responsible for the bystander’s death, but I say if you ‘d done nothing you would be responsible for five deaths). But a very interesting twist to this problem is the ‘Fat man’ scenario:

As before, a trolley is hurtling down a track towards five people. You are on a bridge under which it will pass, and you can stop it by dropping a heavy weight in front of it. As it happens, there is a very fat man next to you – your only way to stop the trolley is to push him over the bridge and onto the track, killing him to save five. Should you proceed?

People who say they would flip the switch often say they would not push the man. It appears that there is some sort of distinction between, as Harris puts it, “throwing trolleys at people and throwing people at trolleys”. The distinction lies in the fact that the Bystander is killed because saving five lives results in his death, and the Fat man is killed in order to save five lives. The embryo researchers are seemingly doing the former – destroying a human embryo in order to save lives – whereas the passengers of United 93 did the latter – saving lives but resulting in the death of innocents.

Don’t worry if you have a hard time working out the difference between these two points. I do too, and so does John Harris (Harris J, 2000). It appears we have evolved to think inactions that cause harm are more acceptable than actions that cause an identical harm. That is, killing is impermissible but letting die is not. But it’s just obvious, if we think about the problem with more than our gut, that choosing to do nothing (i.e. let somebody die) is still an action that results in the death of somebody – you have still killed them.

Therefore, unless there really is a significant difference between doing something because it has good consequences and doing something in order to bring about those good consequences, we are left with absolutely no distinction between embryo research and the United 93 passengers – no distinction between the two train scenarios. It is always permissible to act in a way that brings about the best results for everyone – because you are responsible for your actions, regardless of what you do.

Conclusion

Which brings us back to the original thought experiment, Thomson’s transplant. This would seem to be a case where the doctor kills in order to save lives, but as we have seen this is no different to the doctor killing a person because his death would allow many to survive. But this may still seem a bit extreme for other reasons, such as consent, extrinsic value, pain and so on.

But embryo research is very different from Thomson’s Transplant thought experiment. The donor is not unwilling, nor willing, because embryos do not have a will of their own – adult stem cells can’t consent to their use either, but their therapeutic use is accepted by most. The donor’s mother and father have presumably consented to the use of the embryo in research/therapy (as is current protocol for embryonic research). And embryos cannot feel pain, so this is not an issue.

So I am led to the conclusion that even if human embryos are little people, with a life as valuable as everyone else, embryonic stem cell research and therapy are still the right thing to do. The use of embryos in therapy and research is the action that has the most desirable consequences overall. Unless we believe that killing an embryo is far worse than letting dozens of patients die, then the good ends are sufficiently good to justify the means required to bring about those results. Pro-life groups will need to do more than show embryos are ‘one of us’ if they want to stop embryo destructive life-saving actions.

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GM Human Embryo? Nope, that doesn’t count!

Tuesday, 13 May, 2008

Those at the London Times are conveniently twisting the truth to claim that scientists have created the first genetically engineered human embryo. What did they do? Insert the gene for green-fluorescent protein. Big deal, that’s not what I want to hear when I see the words ‘GM embryo’!

Lots of hype over nothing. This was done last year, and now we finally hear about it. That alone should have you wondering if it had been a blow-up about nothing. If it was an amazing work, the scientists involved would have been calling press conferences and everything.

The embryo wasn’t even viable (it had ‘abnormal chromosomes’ according to the London Times. I think they mean it was triploid), and wasn’t even going to be implanted into a woman. Just a bunch of fluorescent green cells in a dish, destroyed after five days of growth. BORING! There have been stem cell experiments more exciting than this.

It’s only being brought up because the current HFEA bill in the UK actually expresses permission for this research, though it does ban implantation of such embryos.

Reading the comments on the London Times site, and on the other news sites that picked up the story, is fun at least:

“Read your bible people. We are living and acting out every word of revelation’s. , Next thing you know like one comment was made the rich would have perfect babies and the poor , would get thrown to the side like trash .” – Lola of the United States of America (of course)

“These mad scientists are totally out of control, They will completely destroy life on this Planet but before they do this, monsters will be created as in days of old. Which is why that old technology advanced civilisation were destroyed, you cannot mess with nature without being punished.” – Arthur of England

Oh noes, the sky is falling. A bit more sensible, but still wrong, is the commentary from New Scientist:

No-one is contemplating King’s “nightmare” scenario: the creation of genetically-engineered babies.

Actually, I’m contemplating it. So are many others. It’s not a nightmare, it’s a dream!

However, I think I prefer the words of Annalee Newitz over at io9.com, who said:

[Q]uit your whining and learn some science, bitches. This isn’t a designer baby.

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What pro-lifers don’t realise about induced pluripotent stem cells

Sunday, 4 May, 2008

It is often claimed by the pro-lifer crowd that induced pluripotent stem cells (iPSCs) are a great way to sidestep the nasty ethical issues of embryo-derived stem cells. Because, as you all surely are aware, an embryo is a unique human being. But clearly they either don’t understand the science behind iPSCs or don’t think about their pro-life arguments for the protection of the human embryo.

iPSCs are human life

It is often claimed that conception marks the beginning of a new life. But all human cells are alive, just as bacteria are alive. You can kill your own cells, such as killing brain cells by drinking alcohol. These are human cells, as they contain human DNA and would be classified as such. To be strictly true, life began four billion years ago, and hasn’t stopped since. Sperm are alive, and so are ova. There is a continuum of life stretching back to a single point for all creatures (just as all your siblings could be traced back to the zygotes that formed your mother and father, all creatures can be traced back to few cells billions of years ago)

Therefore, as induced pluripotent stem cells are created with the same DNA as would be found in living human skin cells, they are also human life – both human and life. Therefore, if we are supposed to be protecting human life, then we can’t use iPSCs.

iPSCs have a unique human genome

It is often claimed that because the embryo has cells which are distinct from the cells of the mother, they represent a new human being. But if a woman was to receive treatment with iPSCs, they would also be cells that are genetically distinct from the mother, and indeed anyone else on the planet. iPSCs are genetically engineered cells: genetically-modified into becoming pluripotent. A retrovirus is used to insert genes essential for pluripotency, and these can insert in random locations on the genome. Therefore, they contain a unique human genome that would not be found in any other organism. So, if cells with unique human genomes represent humans worthy of protection, then iPSCs are in the same category as embryos.

iPSCs are potentially human beings

I’ve often heard it argued that we should treat embryos as full persons because they have the potential to become full persons (or, because they have ‘inherent capacity’ to become persons). Even if we ignore the the most obvious failure of this argument (young children are potential adults, but it doesn’t follow that we should give them the right to vote. Adults are potential seniors, but they won’t get a senior’s discount. Seniors have the inherent capacity to be dead, but we should not treat them like they are corpses), and assume that something with potential to become a fully functional human being should be treated as such, we are still left with the inability to use iPSCs.

A zygote has the potential to become a human child, but is it not also true that sperm and ova have the potential to become a zygote? And, embryonic cells, and embryonic-like iPSCs, have the potential to form sperm and ova (even though nobody has done that yet). So it clearly follows that if potential is just as good as the real thing, then iPSCs are just as good as you and I. And because any (diploid) adult cell has the potential to become an iPSC, then all human cells are equal to human beings. Unless, of course, potentiality is irrelevant.

In addition, though slightly outside the scope of this blog entry, it may soon prove possible to created induced totipotent cells (iTCs)- that is, to insert genes that would turn a stem cell into a cell identical to a cell found in a zygote. An iTC would have the capacity not only to form sperm which could form a zygote which could form a full human being, but it would also already be a zygote: a clone of person who gave the cells from which the iTCs were derived. So, clearly conception cannot be a significant event, because it is possible to bypass it and end up with a person like you or I.

Conclusion

I don’t actually think iPSCs are worthy of protection. I do, however, think all of these pro-life arguments I’ve heard are useless, as I hope I’ve shown by the reductio ad absurdum above. I think that the right to life is only applicable to a lifeform that is ultimately valuable – that is, valuable to that lifeform itself. To quote British ethicist John Harris

I suggest there is only one thing wrong with dying and that is doing it when you don’t want to. (Harris J, 2003)

A necessary requirement for some organism to value its own life is self-awareness, which is a feature found only in a few brainy creatures (chimps, gorillas, elephants, dolphins etc), and only appears in humans at around 18 months of age. So I tend to agree with those people who say consciousness is a requirement for a right to life, although I would argue that technically it requires at a minimum only one characteristic of higher consciousness – the capacity for self-awareness.

This seems to me to help clear up a common argument put forth against the consciousness view – the protection of humans in subconscious states, such as sleep. Consider an analogous situation. The answer to the question “Does he speak English?” remains the same even though the boy/man may not be English at the time, or may not be speaking at all if he is asleep. If the answer is yes, then this person does have the ability to speak English but isn’t currently doing so. This is not relying on a potential ability to speak English – he is able to speak English. On the other hand, if he has never learned English, it could only be said that he has the potential to acquire the ability to speak English – he is not yet able to speak English, but potentially could be able in the future.

Likewise, you could ask ‘Does he value his life?’ and the answer should not change whether the person is asleep or not currently thinking about their death. On the other hand, an embryo or brain-dead person is not able to value their life, because they have lost that ability or not yet acquired it, but could potentially acquire(or re-acquire) that ability. Consciousness is a state of being, whereas to value oneself is an ability. This is why ultimate value is better than consciousness as an indicator of how much you should respect a person’s life – you can be said to a person even if you are not conscious and therefore not presently doing valuing your life, just as you can be said to be an ‘English-speaker’ even if you are not presently speaking English.

Anyway, the key point here is that iPSCs, and embryos, are not ultimately valuable – they do not yet have a capacity for valuing their own lives, and there is no way to assume they think such an unconscious state as valuable because they have as yet never been able to even have such a thought. And yes, I know that later in life when those cells have turned into you or I they will value their embryonic state in retrospect because it led to their existence, but such people would also value the state when they were comprised of an ovum and sperm, or when they were comprised of iPSCs that were stimulated into making that ovum and sperm – all necessary for their existence (you could even go back 4 billion years). But the important thing is that they have not as yet had the ability to make such value judgements, and as such do not need to be respected. After all, we don’t respect bacteria just because they have the potential to evolve into sentient beings that could, in billions of years, value their prior existence as bacteria.