Saved by the cell

Two recent cases show the progress being made by stem-cell researchers – but their work is still und

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.

Federal funds

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.

Mouse key

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.

Duncan Robinson

This article first appeared in the 29 November 2010 issue of the New Statesman, Congo

Edel Rodriguez for New Statesman
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Rehearsing for war

From the Middle East to North Korea, Donald Trump is reasserting US military strength and intensifying the rivalry among the great powers.

As Vice-President Mike Pence arrived in South Korea from Washington on Sunday, he announced that the “era of strategic patience”, in which the US sought to monitor and manage the nuclear threat from North Korea without pushing the matter for fear of escalation, was over. “President Trump has made it clear that the patience of the United States and our allies in this region has run out and we want to see change,” Pence declared. The heat under a crisis that had already been bubbling ominously was turned up another notch.

Much has been written in recent years about the stability provided by the post-1945 world order and the dangers of letting it crumble. The conflict in Korea provided the first big test of that order almost 70 years ago, but the difficulty was never really resolved. It remains the proverbial “wicked problem” in international affairs, “frozen” in an obsessively monitored and deeply uneasy stalemate, demarcated by the Demilitarised Zone: a line 160 miles long and roughly two and a half miles wide scored across the middle of the Korean Peninsula, drawn with superpower supervision in 1953. Partition has allowed a strong and ­successful state to flourish in the South while the North has survived in a state of ­arrested development.

The problem has been passed down from generation to generation because attempting to solve the issue risked opening a Pandora’s box. The risks included the unleashing of huge military force, potential world war and a refugee crisis on a scale that could severely destabilise even China. By the 1990s, it was clear that the North Korean regime had fastened upon another strategy for survival as the Cold War passed into history and its sponsors in Beijing and Moscow began to question the value of such an ally: the acquisition of nuclear warheads. Pyongyang has long had the firepower to flatten Seoul in a matter of hours. The mission since has been to develop its missile technology to carry that material as far as possible – certainly to Japan, but ideally also to the west coast of the United States.

The day after Pence’s announcement, the US and South Korea undertook a joint air and army exercise to ensure readiness in the event of an attack from the North. This followed a joint naval war game earlier in the week and the US decision to send a navy group led by the nuclear-powered aircraft carrier USS Carl Vinson, which Donald Trump described as an “armada”, to the region. No sooner had the fleet appeared than Japanese sources reported that it had been followed by Chinese and Russian submarines as it entered North Korean waters. Such are the great-power manoeuvres of the 21st century – whether on air, sea or land – in which the world’s most potent military machines shadow the moves of their competitors, and openly rehearse for war.

***

Asia has not had a major inter-state war since the 1970s but it is not immune from the tragedies of power politics that have beset other rapidly developing parts of the world. Across the region, military spending is rising fast as states jostle in anticipation of a changing balance of power.

The purpose of Pence’s Asia-Pacific tour is to offer reassurance to America’s allies in the region, which have been watching the rise of China, in particular, with trepidation. The stark change of tone emanating from the White House – and change of gear – has been noted. After years of steady consistency in US grand strategy, there is a sense of a building crisis and the Americans are being watched in anticipation of their next move more closely than they have been scrutinised in many years.

Before he left South Korea, Pence also visited Panmunjom, where the 1953 armistice was signed at the end of the Korean War, as well as Camp Bonifas, a UN military compound near the Demilitarised Zone, set up to monitor the ceasefire that followed. It is an eerie echo from the past that Pence’s own father served in the war that divided the country. Edward Pence was awarded the Bronze Star on 15 April 1953 for heroic service. The vice-president proudly displays the medal, and a photo of his father receiving it, in his office. He is no doubt aware of the costs of a conflict in which an estimated 36,000 of his countrymen were killed.

Just over a thousand British soldiers also lost their lives in the Korean War after being sent to fight in a joint UN force. But it was far more deadly still for the peoples of the Korean Peninsula, killing more than a million people, including 400,000 troops for the People’s Volunteer Army, among whom was Mao Anying, the eldest son of Chairman Mao, the leader of the Communist Party of China and protector of the North.

History throws up strange parallels. When the Korean War began in 1950 it was understood to be the first serious test of the international system established after the Second World War. It is striking just how many of the same ingredients remain, including the identity of some of the main protagonists. On 25 June 1950, a border conflict between North and South Korea escalated into full-scale war when Kim Il-sung’s Korean People’s Army – backed by China, and with the tacit support of the Soviet Union – invaded the Republic of Korea in the south, claiming that it represented the legitimate government of all Korea. This is a claim that the regime of his grandson Kim Jong-un has not abandoned to this day.

Two days after the invasion, on 27 June, the UN Security Council voted to send a joint force, under General Douglas MacArthur of the US, the former supreme commander of Allied forces in the south-west Pacific area, to protect the sovereignty of the South and repel the invaders. Much more was at stake than the question of territorial integrity or preserving international law. By bringing the Americans into confrontation with the Chinese – and with the Russians seen to be the steering hand in the background – the conflict had all the ingredients for rapid escalation.

From the start, there were concerns that the Americans might overdo the brinkmanship, even under the cautious leadership of Harry Truman. Fears that the self-confident MacArthur would exceed his brief were confirmed when the UN forces pushed back into North Korea in October. In response, the Chinese Communists, who believed that MacArthur had designs on China itself, flooded across the Yalu River in their tens of thousands.

It was in the autumn of 1950 that the danger of another world war, this one involving nuclear weapons, reached its peak. On 28 November, after a grave reverse for the UN forces, MacArthur stated that the advent of 200,000 Chinese had created “an entirely new war”, with much higher stakes than before. Suddenly, the prospect that the US might resort to using an atomic bomb against the North Koreans, or even the Chinese forces, seemed plausible.

While the nuclear scare passed, the war rumbled on towards an ugly stalemate over the next three years. A temporary solution of sorts was found with the 1953 armistice. But there was no resolution to Korea’s frozen war. In a way that no other totalitarian state has managed, the North zipped itself into a hermetically sealed chamber, preserving a three-generation dictatorship that is both comically anachronistic and frighteningly modern in its missile technology.

***

Some of this complicated backstory was explained to Donald Trump by China’s president, Xi Jinping, during his recent visit to the United States. Trump – who had been pressuring China to do more to deal with the North Korean regime – appears to have been receptive to what he heard.

“After listening for ten minutes,” he said, “I realised it’s not so easy.”

This is the first critical test of the “new era in great-power relations” which Xi has been floating for a number of years, but Trump has now decided to put to the test. According to Trump’s most recent tweets, Beijing has continued to work with the US on the North Korea problem. He has welcomed its contribution but insisted that America’s own willingness to deal with the problem does not depend on China. In other words, there is no master plan being played out here, even if – as seems credible – America did hack North Korea’s latest missile launch to make it a damp squib.

The Trump administration is not creating the conditions for a new long game, building a fresh multilateral consensus to contain the North Korean threat. Instead, with a newfound sense of momentum serving as a tail wind, it senses a moment to “solve” one of the longest-running and most treacherous problems in international affairs. It has decided, at the very least, to severely clip the wings of Kim Jong-un’s regime. And in doing so, it has set out to demonstrate that when America speaks, it speaks with effect.

Like much current presidential policy, “the Trump doctrine” is being made on the hoof. Much of the hyperactivity of the past month or so was not scripted but emerged in response to overt challenges – beginning in Damascus and panning to Pyongyang – to the United States and the “red lines” it has laid down in the past. One foundation stone of Trump’s approach to the world is firmly in place, however: the willingness to reassert US military power with swift and decisive effect. The idea that the “America First” slogan implied anything resembling isolationism is crumbling. The growing sense that it does imply unsentimental and unvarnished power politics in the name of the US interest rather than multilateral niceties is closer to the truth.

Under Barack Obama, the US sought to withdraw from those areas in which he felt that the US had overstretched itself under his predecessor. Obama opted for a more rapier-like and cost-effective form of power projection. He drew down from formal military operations in Iraq and Afghanistan, while presiding over a huge uptick in drone warfare, cyber capabilities and selective but deadly use of special operations. Much of the full range of US power was submerged in various “secret wars”, and the diplomatic compass was reset to pivot east. This was because, as a legacy of the 9/11 attacks, national security was geared towards the containment of an elusive and amorphous enemy – various offshoots of the global jihad movement – that operated on the periphery of America’s radar.

But the real metrics of great power are those now on display off the coast of North Korea. For all the advances in drone technology, the missiles that cause the gravest threats to humanity are those on the scale that the North Korean regime is attempting to build. Trump’s test was one that a president of the United States would have to face sooner rather than later.

Not since Ronald Reagan has the US been so willing to engage in naked displays of its own military potency in quick succession – and seek to gather diplomatic yields from them as swiftly as possible. The past fortnight brought a missile attack on an airbase manned by the Assad regime – changing the tenor of US-Russian relations overnight – and the dropping of the so-called Moab (“mother of all bombs”) on an Isis affiliate in Afghanistan. The latter was a far cry from the “clear, hold, build” counterinsurgency operations in vogue half a decade ago. But it did fit with a campaign promise by the new president that he would “bomb the shit out of Isis” should the opportunity arise.

Does this fit into a wider pattern or constitute a new approach? The Trump administration is eager to leverage any opening that might have been created. In Seoul, Pence wasted no time in joining the dots: “the world witnessed the strength and resolve of our new president in actions taken in Syria and Afghanistan”. North Korea, he continued, “would do well not to test his resolve, or the strength of the armed forces of the United States in this region”.

It is the generals who have increasingly set the tone for Trump’s foreign policy. During the 2016 election campaign, he promised to give the Pentagon more leeway than it had under Obama to focus on “winning”. The new national security adviser, H R McMaster, and the defence secretary, General James Mattis, are now the steering hands.

Neither man has followed the rather crass and short-sighted fashion for running down diplomacy. Mattis once said that if the state department budget was cut, he would need more ammunition. McMaster is an urbane thinker who knows that the use of force must always be carefully calibrated and is just one tool in a continuum of factors. In this respect, it is a problem that so many jobs in the state department remain unfilled. Now that muscle has been flexed, the experienced negotiators and diplomats should be flooding through the door.

***

The policy of “strategic patience” was based on an understandable calculation. But, in hindsight, it does appear that North Korea has suffered from neglect. Mitchell B Reiss, one of the most experienced diplomats who led efforts on North Korea in the 1990s, notes that, despite unprecedented co-operation between the US and China in recent weeks, including open threats of economic pressure and military action, they were still unable to prevent North Korea from testing ballistic missiles on 16 April. Even though the missiles exploded immediately after lift off, “The failure of Washington and Beijing to stop the test in the first place has important implications for the Trump administration’s future policy options and for stability in north-east Asia.”

In Reiss’s view, it is “highly unlikely that the North can be cajoled, threatened or given incentives to surrender its nuclear weapons”. The uncomfortable truth is that “short of regime change, which could inflame the entire Korean Peninsula in war”, the US cannot halt the North’s nuclear weapons programme. But that does not mean there are no options. Slowing the pace and raising the costs would be “prudent steps”. More, too, could be done, Reiss says, to “interdict imports of sensitive technologies, to sanction Chinese and other nationals who act as purchasing agents for the nuclear and missile programmes, and to punish Chinese banks that help finance these programmes through so-called secondary sanctions”.

In the end, so much comes down to US-China relations. Could this be the basis for a reset and a new accommodation between Beijing and Washington? How much further is China willing to go to use its leverage on the North, which depends on it for energy and food? And how patient will the Trump administration be if its new strategy does not yield tangible results of the sort that are sometimes elusive in the long and often open-ended game of deterrence? 

John Bew is a New Statesman contributing writer and the author of “Realpolitik: a History” (Oxford University Press)

John Bew is a New Statesman contributing writer. His most recent book, Realpolitik: A History, is published by Oxford University Press.

This article first appeared in the 20 April 2017 issue of the New Statesman, May's gamble

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