Posts Tagged ‘embryonic stem cells’


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.


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.


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.


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.


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.


Positive feedback loops in bioethics

Wednesday, 23 April, 2008

There are some situations in bioethics were people use a prior action has justification for further actions. I like to call these positive feedback loops, as they remind me of the positive feedback mechanisms of the body; an increase in one property (say, the level of a hormone) causes a set of signals to be releases that cause that property to change in the same direction as the initial perturbation. In economics, such loops are called ‘vicious circles’, such as where lack of education leads to a lack of income which leads to a further lack of education leading to a further loss in income and so on.

The most obvious loop is that involved in the debate about human embryonic stem cell research. These were banned or restricted (by limiting funding) in many places around the world, and many researchers no doubt shied away from the field due to the funding or legislative insecurity. Unsurprisingly, there have been far more treatments developed that involve adult stem cells than those using embryonic stem cells. Detractors of embryonic stem cells claim this lack of results is due to the inferiority of embryonic stem cells, and without the push for therapies, the restrictions on embryonic stem cell research are not likely to change, and could even be increased.

Similar examples involve agricultural biotechnology, where harsh restrictions GM crops causes them to be far more expensive and less efficient to grow, which weakens claims about solving the food crisis, which removes the major reason for allowing the research, which causes restrictions to increase.

I’m worried a similar problem of this sort could arise with human enhancement technologies, like genetic modification. They will first be banned for ethical problems or safety concerns. Then a few researchers will begin their research in other nations where there are no safety concerns or clinical trials, leading to horrible experimental disasters unrivaled in sci-fi films. Then those experiments will be exposed to the public, leading to mass panic. This social pressure will leading to even harsher restrictions on the research, driving the research even further underground, thus restarting the cycle again.

We need to watch out for these loops. It is entirely unscientific for people to claim that stem cells are better derived from adults than embryos if both are not on equal footing. It is entirely illogical for people to claim that growing GM food is more expensive if their concerns about GM food are what made it so expensive in the first place. And, it is especially bad to force research underground where it will be carried out in a manner unsafe to both the researchers and the research subjects, and illogical to believe such research would be equally dangerous if carried out in approved facilities under regulatory oversight. These loops can quickly spiral out of control into a land of very, very harsh restrictions on scientific research. And I, for one, would much rather have too much science than too much legislation.


German Parliament changes stem cell law

Saturday, 12 April, 2008

An update to the story I blogged about a couple of months ago regarding proposed changes to Germany’s stem cell laws. The proposed changes were just approved.

In brief, under German law (the Stem Cell Act of 2002) no embryos can be destroyed for research, but they were allowed to import embryonic stem cells lines created before 2002. But, of course those stem cell lines would have been created with inferior technology and knowledge, so scientists from the German Research Foundation lobbied to get the laws changed slightly to allow importation of more recent stem cell lines.

The law was passed yesterday, so now embryonic stem cell lines created before May 2007 are allowed to be imported into German.

It’s a minor loosening of very strict laws, but I guess any improvement is good news.


Comments on Britain’s cybrid ‘part human, part cow’ embryos

Thursday, 3 April, 2008

Researchers at the University of Newcastle have announced that they created human-animal hybrids! What do we say to that?

My response – a rather unimpressed “that’s nice”. Despite all the press it is getting, there are some important things to remember:

  • This is not new – human-animal cybrids were first created over five years ago, by Huizhen Sheng at the Shanghai Second Medical University, China. They used anucleated rabbit cells and inserted the human nucleus into those to create stem cells. It is the first time this was done in European labs though, so in that respect it is a first.
  • This is just for stem cells – for some reason, hopefully just safety concerns, it is illegal to implant human-animal cybrids (and human-human cybrids in some countries). The cells were therefore destroyed at the blastocyst (because as you surely know, a blastocyst will die unless it is implanted).
  • Cybrids are not a different species – cybrids differ only in their source of mitochondrial DNA. They are the same species as their nuclear DNA, meaning that a human nucleus inserted (properly) into an anucleated bovine cell will grow into a perfectly normal human embryo, and if implanted will grow into a human being capable of reproducing with any other member of the human species.
  • On that note, the cybrid will not act like animal – human nuclear DNA controls almost everything that DNA can control, so if these human-bovine cybrids were implanted and grown to term, they would not have an udder, they would not have horns or hoofs and they would not be making cow’s milk (females would be capable of making human milk though). They would human, and you wouldn’t even be able to tell them apart from anyone else. It is possible that some problems could occur due to the foreign mitochondrial DNA, but they are not going to be problems of the bovine variety.
  • A cybrid (cytoplasmic hybrid) is different to a true hybrid – a true hybrid is created by mating two species. A cytoplasmic hybrid is just inserting the nucleus from one species into the the cytoplasm from another. Because all of the cytoplasm, except for the mitochondria (which reproduce by themselves), is a product of things produced by the nuclear DNA, after just a couple of days only the mitochondria are still foreign in origin.

So get over it people. I mean, it’s cool that British researchers have had success in this difficult procedure, but not enough to get upset about. It’s certainly not an experiment of “Frankenstein proportion”.


How to determine the status of human embryos

Wednesday, 2 April, 2008

This bioethics twist on the classical ‘fat-man trolley problem‘ of moral philosophy can be used to determine whether a person considers embryos to be full human beings or not, and exactly how much of a human being an embryo is. So, here it is:

A train is hurtling down a track, and on this track is a single railway worker, unaware of the train. You are on a bridge under which the train will pass, and you can stop it by dropping a heavy weight in front of it. For reasons unknown, there is a refrigerator (from the local IVF clinic) on the bridge next to you, which you know contains a thousand human embryos – your only way to stop the train is to push the refrigerator off the bridge and onto the track, killing all thousand of the human embryos to save the life of the railway worker. Should you push the refrigerator off the bridge?

If this seems confusing, there is another very similar example that may make more sense because of its more realistic premise (though, technically, it is a version of the original trolley problem, not the fat man version):

Imagine that an IVF lab is on fire. A fireman realises that the roof is about to collapse and that he has very little time left, only enough to rescue either a tray of 1000 frozen embryos, or the lab technician, who is already unconscious because of the smoke. What should the fireman do?

To determine the moral status of a human embryo, all you must do is vary the number of embryos until it becomes immoral for them to be destroyed in the process of saving a life. Let that number of embryos be [E], then the perceived status of the embryo is PS, given by:

PS= 1/[E]


PS = perceived status of the embryo (1 is a full person, 0 is not a person at all)

E = number of embryos required to make their destruction in saving a single adult’s life morally unacceptable

The result you get from this thought experiment essentially can determine whether you are in favour of using human embryos in medical research or not (like embryonic stem cell research). The higher your PS score, the more likely you are to oppose embryo-destructive treatments and procedures. The lower your score, the more likely you are to be in favour of using human embryos to discover treatments for human diseases.

The fun part is when people hold the wonderfully contradictory position of having a low PS score but are hostile to embryo research (I’m sure the reverse is possible, but I don’t know anyone who holds it). Sparks fly with accusations of hypothetical hypocrisy!


Therapeutic cloning can also cure!

Monday, 24 March, 2008

Researchers have used therapeutic cloning to cure Parkinson’s disease in mice. This is a landmark study, published in Nature Medicine, because the embryonic stem cells were cloned from the patients that they later cured.

The researchers, led by a team at the Memorial Sloan-Kettering Cancer Center in New York, USA, used the classic cloning technique – somatic-cell nuclear transfer (SCNT). The nuclei from skin cells from the tail of the mice were inserted into anucleated ova, to create the cloned mouse embyros from which the stem cells were derived. The stem cells were differentiated into the dopaminergic neurons of the basal ganglia that are damaged in Parkinson’s.

Test animals were artificially given Parkinson’s disease, whereby the above-mentioned dopaminergic neurons were lesioned by chemicals. The neurons derived above were transplanted into the basal ganglia of the mice. Those mice that were treated with neurons derived from embryos cloned from their own tail recovered well within eleven weeks, but those receiving neurons from other stem cells lines were not significantly better eleven weeks later. This confirmed the advantage that therapeutic cloning has – the stem cells will be genetically matched to the individual, overcoming the problems with immunological compatibility.

But, just to satisfy those opposed to cloning and embryonic stem cell research, the researchers said that they are now going to see if they can use the embryonic-like cells that have been shown to be able to be derived from skin cells.



Only embryonic stem cells secrete cancer-busting protein

Tuesday, 4 March, 2008

Researchers at Northwestern University in the USA have found that human embryonic stem cells secrete a protein, called Lefty, that blocks the formation of some skin cancers (e.g. melanoma) and breast cancer. Now the researchers have looked at placental cells, amniotic stem cells, cord-blood stem cells andadult haematopoietic stem cells, but none of them have been able to do what the eSCs do – prevent cancer.

From what I could gather by reading the article, the protein Lefty appears to block a protein, Nodal, produced by cancers. Nodal is hypothesised to be a protein that causes the cancer cells to continually divide, and Nodal is somehow blocked by Lefty. The researchers added tumour cells to embryonic stem cells, and within 3 days (for the melanoma) to 5 days (for the breast cancer), the tumour cells had stopped producing Nodal. Without Nodal, the cancer cells entered apoptosis (cell suicide).

So, now when asked the question “what can embryonic stem cells do anyway?”, you can respond with “Oh, nothing much. Just cure both melanoma, the cause of the majority of skin cancer deaths, as well as breast cancer, the fifth most common cause of cancer death in the world.”

(Link to Full Article not yet available, despite what the ScienceDaily summary says. I think they get confused with the other NWU story, in PNAS this week. So, look at some earlier work on Nodal pathways, similarity between embryonic cells and cancer cells and the effects of embryonic microenvirons on metastatic tumours)