In early October, someone – we don’t know who – in or around Atlanta, Georgia, became paralysed. This is not exceptional – spinal injuries paralyse 12,000 Americans each year. The victim, however, is exceptional: for this is the first person to receive a treatment that might restore his or her damaged cells. Imagine, then, how that patient feels to know that a nearby judge is considering forcing the American government to stop funding further research into this treatment because it uses embryonic stem cells (ESCs).
There has been so much fuss about ESCs that it is startling to realise that this patient in Atlanta was the first person to get them. But he was not alone for long. On 16 November, doctors in Glasgow announced that they had injected a slightly different kind of stem cell into the brain of a man disabled by a stroke.
The trials will continue. The next few years are their make-or-break time. The bottom line is that stem cells are not yet a panacea. Many scientists are convinced that they could be used to treat injured spines and brains – as well as diabetes, Parkinson’s, Alzheimer’s, MS and other conditions. Yet research is under renewed threat after Republican victories in the US midterm elections reinforced opposition to it.
We all start as a clump of identical cells. Their descendants then differentiate into our 200-odd specialised components – nerve cells, blood cells and the rest. But if you lose nerve cells, nearby blood cells do not revert to their embryonic state and re-differentiate into the nerve cells that you need. Very early embryonic cells, however, can become anything. ESCs come from surplus embryos created during in vitro fertilisations – abortions, as far as the US religious right is concerned. They are coaxed to become differentiated cells that can, in theory, be given to those in need: insulin-producing cells for diabetes patients, for example.
Geron Corporation of San Francisco has turned ESCs into a kind of cell that insulates nerves. In most paralysing spinal injuries, says Anna Krassowska of Geron, it is those cells that are damaged. If Geron’s cells are injected into rats soon after such an injury, they restore some normal movement. But the trial in Atlanta must first ensure that they are safe in humans: ESCs can become confused and proliferate into an unhelpful mass. So the team is waiting, Krassowska says, to see if the cells behave, before starting on a second patient.
Geron’s cells were taken from an embryo created before 2001. On 9 August that year, President George W Bush decreed that federal funding could be used only for work with the 21 lines of ESCs already established. Hundreds of new lines, with useful genetic differences, have since been established – but US scientists could not use federal money to study them.
Funding does exist elsewhere: Glasgow is a case in point, while the London Project to Cure Blindness hopes to treat age-related degeneration of the retina with ESCs by 2012. But the political uncertainties have stifled private investment in stem cells, analysts say, while the sheer scale of US science funding meant that the ruling was a blow. “Federal funding just for work with those 21 permitted cell lines between 2001 and 2009 was still more than the rest [of the funding] put together,” Chris Mason of University College London tells me.
In 2009, President Obama lifted the restrictions. But in August this year, a US district court halted ESC research under a budget law banning the use of federal funds to destroy human embryos. If the decision is upheld, government-funded ESC work, even on previously permitted lines, must stop. Plaintiffs in the case charge that ESCs take funding away from research on non-embryonic stem cells, an argument that anti-abortion groups have seized on.
Non-embryonic cells are already used therapeutically. Doctors can culture a patient’s own skin or cartilage cells to create grafts or rebuild windpipes. But these are differentiated and are not stem cells. Bone-marrow cells that normally generate blood cells are stem cells, however, and have been transplanted routinely for years. Similar, relatively undifferentiated “adult stem cells” are thought to lurk in most organs, capable of becoming that particular tissue. Such cells in the eye are used to regenerate corneas after chemical burns. In humans, these cells do only so much and there are lots of tissues we can’t regenerate. The long-term hope is to induce them to do more – maybe even regenerate lost limbs. This is fine with those who oppose ESCs, but it’s also far in the future.
More immediately, cells in the developing human foetus, at a later stage than embryos, are already committed to a certain range of types – skin and nerves, say – but are still flexible. These sorts of cells, from a line derived by ReNeuron, based in Guildford, were injected into the stroke victim’s brain in Glasgow. However, their foetal source means they attract the same opposition as ESCs.
Induced pluripotent stem cells (IPSCs) are another story. These are differentiated cells that have been turned back into something like embryonic cells by reversing four kinds of chemical change in their DNA. It is IPSC research that plaintiffs in the US legal battle claim is unfairly deprived of funding by work on ESCs. Many hope that IPSCs will make ideological opposition to other stem cells moot. “It is understandable that individuals should feel uneasy about the use of foetal cells,” says Darren Griffin, professor of genetics at the University of Kent. But IPSCs “have the potential to get around many of these ethical concerns”.
The key word is potential: IPSCs are far from ready. Differentiation flips thousands of chemical switches in a cell’s DNA. Flipping just one the wrong way can make a normal cell into a cancerous one – and we don’t know where all the switches are in any given IPSC, Mason says. “In ESCs, we know where they are.” There’s also something not quite right about current IPSCs. You can breed a normal-looking mouse from them – but it doesn’t live long. Does this make them unsafe for repairing a broken spine? We don’t know yet. But for ESCs, we soon will.
The supposed choice between funding foetal or embryonic stem cells and adult ones seems more ideological than scientific. “We need to work on all avenues,” Mason says. Future IPSCs or adult stem cells – or even remodelled differentiated cells – may one day work better for certain things than ESCs or foetal cells, especially if they are a patient’s own. “But research on ESCs is ten years farther along,” Mason says. “We’ll lose what we’ve already learned if we stop working with them.”
For now, ECSs and foetal cells present the best hope of success soon. And a few successes, researchers hope, could change everything. If the kind of cells now settling into a spine in Atlanta and a brain in Glasgow can make the lame walk and the blind see, ideological objections might melt away as they did for in vitro fertilisation. How soon that happens depends partly on what happens in a US courtroom.
Debora MacKenzie writes for the New Scientist
The American right to life
When the scientist James Thomson and his team first succeeded in isolating human embryonic stem cells at the University of Wisconsin-Madison in 1998, they inadvertently triggered a debate that has dominated political discourse in the US. In the index of George W Bush’s memoir, the stem-cell controversy receives more mentions than Osama Bin Laden.
Arguments over stem-cell research have emerged as a virulent offshoot of the abortion debate, with pro-life campaigners seizing on stem-cell research as another assault on the sanctity of life. Bush’s decision in 2001 to limit such research was challenged repeatedly by Congress, which tried to pass bills opening up research in 2005 and 2007, when the house was under Republican and Democrat control respectively. Despite Barack Obama’s reversal of the restrictions, the issue has not been put to bed.
The recent success of the Republican Party in the midterm elections has been powered in part by the pro-life Tea Party movement. It is unlikely that the current Republican-controlled Congress will support the liberalisation of research.
Advocates of stem-cell research have high-profile backers such as the actor Michael J Fox, who has Parkinson’s. But they will need to speak loudly to be heard over the resurgent right.