Wolverine from the X-men is pretty awesome. Not only does he have a hairdo to die for and claws coated in adamantium (ask you nearest nerd), he also has the power to self-heal. As a naturally clumsy person, if I could pick a superpower then regeneration would be amongst my top choices, along with the clichéd invisibility and maybe a super-human metabolism. Excitingly, whilst many superhero powers remain just that, super, a breakthrough in stem cell technology may have brought us mere mortals a step closer to mimicking Wolverine’s healing powers*.
The technology in question involves generating a specific type of cell, called an embryonic stem cell (ESC). These cells are special because they are the only naturally occurring cells capable of becoming any and every cell type in the body, a property known as pluripotency. In nature, they are found only in embryos in the very earliest stages of development, and give rise to the entire body from a tiny number of cells.
Research into ESCs has great potential for human therapy because, if we could harness their power, we may be able to regenerate failing organs and tissues, allowing a ‘natural’, Wolverine-style repair process to occur. Their pluripotent nature means that we could instruct them to become any cell type needed, from new retinal cells to cure blindness, to new heart cells to replace damaged heart tissue. However, the scarcity of the cell type makes them incredibly hard to come by ordinarily. What’s more, because they are only found in early-stage embryos, harvesting ‘natural’ ESCs for research is very controversial, as it requires experimentation on aborted fetuses at early stages of growth.
The new stem cell technology aiming to provide an alternative means of generating ESC cells is known as Somatic Cell Nuclear Transfer (hereafter called SCNT so we don’t all go mad). Scientists from Oregon Health and Science University extracted the DNA from a human skin cell donor. They placed this donor DNA into a human egg cell that lacked any DNA of its own. The egg cell was treated with different proteins in such a way that it was coerced into becoming reprogrammed stem cell which began to develop into an early-stage embryo, making ESCs. The ESCs could then be collected and grown separately on petri dishes.
This research is exciting in the scientific community for several reasons (although to be honest, it takes surprisingly little for scientists to get excited). Firstly, SCNT could provide a more ready supply of ESCs for investigation and implementation of regenerative therapies. Secondly, because the technology uses skin cell DNA, which is very easy to obtain with a simple swab, a new batch of ESCs would be made for each patient that needed them. This would mean that the new cells would have the same DNA as the other cells of the body, which should eliminate the risk of immune rejection.
It sounds great, but there is a fly in the ointment. You may have realized by now that what we’re talking about is in essence human cloning. The newly generated embryo could in theory become a human being, who would have the same DNA as the person who donated the skin cells. In fact, the technology has been used in animals for over a decade to create clones such as world famous ovine Dolly the sheep. Of course, this makes the research somewhat contentious. As always, with great potential for good comes great likelihood of cries of ‘this is an outrage!’ But do the naysayers have a right to be worried?
The first thing that is important to make clear is that, although this is technically cloning, as the ESCs have exactly the same genetic material as those of the skin cell donor, what has been achieved is nowhere near to creating a fully grown human clone. During the media frenzy surrounding the birth of Dolly, there was a lot of talk about the generation of human clones as though the breakthrough was imminent. But what this scaremongering failed to take into account is that SCNT technology has been around since 1962, when the British developmental biologist and all-round science legend John Gurdon used the technique to produce cloned frogs (incidentally, his contribution to science was recognised this year when he was awarded the Nobel prize for medicine for his frog cloning research).
The thing is that as we have long suspected, we humans are special. Fundamental differences between egg cells in primates versus other vertebrates means that it has taken of a decade of research since Dolly was made to get past the very first hurdle of human cloning: generating ESCs that don’t immediately die. In the present research, the scientists have generated cloned embryos that grow and divide up to the 150-cell stage before they are taken apart and the ESCs grown separately. The human body has around ten thousand billion cells. So it’s easy to see we’re not there yet.
It’s fair to say that the use of embryos for this kind of research often makes people uncomfortable, no matter how early their growth is stopped. But, to put as little perspective on this, British law currently permits abortion up to 24 weeks into a pregnancy, by which time the embryo has billions of cells, as well as fairly well formed facial features, a heartbeat, fingernails and developing lungs. 150-cell embryos are in no way viable. Nonetheless, the slow development of human SCNT technology has meant that scientists have been exploring other avenues of stem cell technology.
Currently being used in the UK, adult stem cells are a much less controversial cell pool with many useful properties. Adult stem cells have the potential to give rise to many, but not all, cell types in the body. For example, haematopoetic stem cells, found in the peripheral blood and bone marrow, are responsible for the daily renewal of blood and immune cells. Bone marrow transplants utilise the power of haematopoetic stem cells to replenish the patient’s blood supply with healthy cells. Nowadays HSCs can often be obtained from the blood instead of the bone marrow, and are used to treat cancers such as leukemia and lymphoma. The downside of adult stem cells is that, as they are more restricted than the pluripotent ESCs, they have more limited uses.
In the last few years, one more possible alternative to SCNT has arisen: the artificial generation of pluripotent cells in the lab. The cells, called induced pluripotent stem cells (iPSCs) are made from ordinary adult cells which are forced to turn on and off the same genes as an embryonic stem cell. iPSCs can then be grown on petri dishes, meaning that they don’t require the initial growth of a cloned embryo. In 2012, scientists managed to generate human iPSCs from kidney cells extracted from urine. This means that, if iPSCs were to be used in regenerative medicine, they could be generated from readily available sources. Not only would this avoid the controversy generated by ESCs, but it would also overcome one other major downfall of SCNT – the need for human egg cells. Egg cells are relatively rare, must be donated by a person rather than grown in the lab, and must be of extremely high quality to produce good quality ESCs. iPSC technology sounds perfect, but, alas, recent research has suggested that iPSCs may be inferior to ESCs, as they tend to have genetic abnormalities which may affect their ability to produce other cell types of high quality. Whether this technology can be harnessed for use in regenerative medicine remains to be seen, but for now, SCNT may be the better bet.
Many argue that use of SCNT technology is a slippery slope, that we are paving the way for a future in which genes can be picked at random, loved ones brought back from the dead and armies of human clones generated by unstable nations. To these people, I would say: first, stop reading so much science fiction and get out of the house more. Second, it is true that there are inherent dangers when developing this kind of technology. But, because cars kill on the roads, does that mean they should never have been produced? Or, to take a more biological example, because botulinum toxin (the stuff used in botox) could potentially be used as a weapon in biological warfare, does that mean that we should stop investigating whether we can use it to help patients with cerebral palsy?
If we are to improve quality of life through scientific research, at some point we have to trust that we will know when enough is enough. Is does not seem remotely likely that, because the technology is available, the government will suddenly approve human cloning. And it is hard to believe that there are many scientists out the who would want to see it achieved, although of course there will always be a minority who desire ‘progress’ at any cost. Instead of fretting about unlikely ‘what ifs’, we should celebrate this benchmark in stem cell technology for what it is – a step on the road to regenerative medicine. This month, we find ourselves closer to superhero status, a little more like Wolverine.
*Disclaimer: Not actually at all like Wolverine’s powers