Organ transplants: Could advances in cross-species donors and lab-grown body parts offer hope for the future?

Hundreds of people die each year while waiting for transplants and the number of available organs is falling. 

Jeremy Laurance
Monday 19 October 2015 18:20 BST
Ella, six, pictured with her mother Alice, had to wait six months for a heart transplant
Ella, six, pictured with her mother Alice, had to wait six months for a heart transplant (True North Productions)

Six-year-old Ella had been waiting for a heart transplant for six months. At one in the morning, her parents Alice and Darren got a call from Newcastle's Freeman hospital telling them there was a potential new heart for Ella and asking them to bring her in within half an hour.

It was an emotional moment for Alice. “I broke down and cried and cried. We had been waiting a long time,” she says.

Ella was born with a congenital heart defect and had already had three major operations. A transplant was her last chance of life. For her family, that was worrying enough. But for others in their position it is worse. The outlook for children such as Ella, whose story is told in The Gift of Life, a new Channel 5 series on organ donation starting tomorrow night, is deteriorating.

Last year, for the first time in a decade, the number of organ donors dropped. Just 182 heart transplants were carried out in the UK, 12 per cent down on the previous year. The number waiting for a new heart has more than doubled in five years. Overall, 224 fewer patients received life-saving or life-transforming transplants in 2014–15, a 5 per cent fall on the previous year. For 429 patients, time ran out – they died while on the waiting list.

In part, this is good news. Fewer people are dying in accidents and advances in medical care mean more lives are being saved. The decline in donors can be seen as evidence of social and medical progress. But it is hard to sustain this argument in the face of the number of potential donors whose organs are going to waste. There are almost 7,000 people on the transplant waiting list, plus a further 3,300 who have been temporarily suspended from it because they are too ill to undergo a transplant operation. On present trends, little more than 4,000 will get the organ they need by the end of the year.

Among the 250,000 people who died in UK hospitals last year, fewer than 1,300 actually donated organs (up to eight recipients can be helped – with heart, kidneys, liver, lung, bowel, corneas – from a single donor).

A question of consent: the crisis in transplantation is intensifying around the world as demand is rising but the supply of donors is failing to keep pace (Getty)

Despite real success in boosting the number of deceased donors, up 68 per cent since 2005, still just 30 per cent of the UK population are on the Organ Donor Register, indicating their willingness to give their organs in the event of their death. As 90 per cent say they support organ donation, there is still a long way to go. The number of living donors – mainly those giving a kidney to a relative or friend, who account for half of all transplants – increased sharply to 2010, but has since levelled off at just over 1,000 a year.

The crisis in transplantation is intensifying around the world as demand from ageing populations for replacement body parts is rising but the supply of donors is failing to keep pace. Desperate people are driven to desperate measures and there is a growing international trade in organs, which is illegal in most countries, with patients who can afford it travelling abroad to get the transplants they need.

In response to the crisis, doctors, policy makers and scientists are urgently seeking solutions, including boosting the number of donors and finding new sources of organs, either from animals or by growing them in the laboratory. Among the most radical is a change in the law being introduced in Wales this year. Instead of requesting the public to “opt in” to organ donation by joining the organ donor register, from December, Wales will operate a form of “presumed consent” requiring members of the public who object to having their organs used after death to “opt out”.

An opt-out scheme already operates successfully in Spain and Belgium, two countries with high rates of donation. Welsh ministers hope the measure will boost transplants by a quarter, although the Welsh scheme will be a “soft” opt out – meaning that if family members object to having their relative's organs used, the transplant will not go ahead.

The expectation is that people will be more likely to follow the default position and do nothing rather than signing the register to opt out – thus making their organs available for transplantation after their death. Critics warn, however, that this risks undermining the vital relationship of trust between doctors and patients if doctors can take organs without specific consent.

The test for the Welsh scheme will be whether it successfully boosts the number of donors by a significant degree. If it does, pressure will grow for its introduction in the other countries of the UK. If, on the other hand, it causes protests, it could damage the transplant programme. A death in the family is a time of high emotion and consent is vital before any intervention. The sensitivity of the issue was seen in the Alder Hey scandal in the 1990s, when the bodies of babies who had died at the Liverpool children's hospital were systematically stripped of their organs for research, without their parent's knowledge or consent, provoking public outrage.

It is also seen in the transplant community when relatives refuse to allow the organs of a loved one to be taken after their death, even though the deceased person had expressly consented by adding their name to the organ donor register before they died. In one in 10 cases where suitable donors whose names are on the register are identified, relatives overrule their wishes and refuse consent.

Elisabeth Buggins, chair of the UK Organ Donation Taskforce, which reported in 2013, said the level of family refusals was unacceptable. She said it should be mandatory for doctors to refer a potential donor to the NHS Transplant service if their name appeared on the donor register. Although doctors had a duty to support the family and do what was right for them, “they have not done enough to support the wishes of those who have died,” she said.

The taskforce report proposed a change in the handling of relatives' opposed to donation, among 40 recommendations aimed at boosting the supply of organs. It also called for changes to the hospital tariff to “reward best practice”, and the withholding of merit awards from consultants who failed to refer potential organ donors. These moves were seen as a means of redressing the wide variation in referral rates around the country.

For some experts, however, the report did not go far enough. They have called for a trade to be established in organs. Transplant tourism has existed for many years, with wealthy Western patients travelling to parts of the world where the market in organs is tolerated, or ignored, and life is cheap. Better to make it legal so it can be properly supervised and regulated, they say. Only in this way is the global demand for organs likely to be met.

In Iran, payment for organs is permitted, but in consequence very few people donate their organs freely. In Israel, there are low numbers on the organ donor register, resulting in a high rate of transplant tourism, with wealthier patients travelling to countries in eastern Europe to buy organs. To boost numbers on the donor register, the Israeli government offered those signing up a cash incentive or priority for a transplant, should they need one. The public chose priority for transplants over the cash.

Selling organs is banned in the UK, as in many other countries. However, our attitudes to cash payments are inconsistent, as the Nuffield Council on Bioethics, which examined the issue in 2010, observed. Paying for organs and for blood is illegal but egg and sperm donors can receive expenses. Women can receive free fertility treatment worth thousands of pounds in return for donating some of their eggs and volunteers who “donate” their bodies for medical research, such as testing new drugs, are paid thousands of pounds in cash.

The Nuffield Council recommended that the NHS test the idea of offering a cash incentive to organ donors in the form of payment for their funeral. Altruism should continue to be central to all types of donation, but that did not rule out allowing some form of payment in some circumstances. Funeral costs are a burden that can weigh heavily on the elderly as they approach the end of their lives. No harm could come to the donor, it said, and it would be a form of recognition from society.

Alongside these policy initiatives, scientists continue to seek the holy grail of transplantation: a new source of replacement organs, that would be safe, effective and abundant. The options are to “farm” organs by growing them in specially bred animals – the pig is favoured because its organs are about the same size as ours – or to grow them in the laboratory from the patient's own cells.

At the turn of the millennium, scientists held out a real prospect that the global organ shortage could be solved by a network of “organ farms” where white-coated technicians would raise herds of genetically modified pigs in sterile conditions to provide an unlimited supply of hearts, kidneys, and livers for transplant into humans whose own organs had worn out or failed. But the twin challenges of immune system rejection and fears about viral transmission proved insuperable, and the programme ran into the sand.

More than a decade on, hopes were dramatically revived earlier this month when scientists announced they had used the new gene-editing technique Crispr to sharply reduce the risk of a transplanted pig organ carrying a virus that could infect its human host, and claimed the same method might be used to overcome rejection.

Fears that the use of pig organs in transplants could trigger a new disease in humans has been one of the chief barriers to progress. Pigs harbour retroviruses that cause no harm to the animals themselves but which could theoretically emerge in another species, such as a human host. Aids is caused by a retrovirus – HIV – transmitted to humans from monkeys, and some scientists have raised the terrifying spectre that transplanting pig organs could trigger a similar pandemic.

Now, researchers led by geneticist George Church, from Harvard University, have described in the journal Science how they used the powerful gene-editing technique to destroy potentially harmful DNA sequences at 62 sites in the pigs genome. The group has since gone further and created pig embryos with inactivated retroviruses, Professor Church told a National Academy Sciences meeting this month.

Experts hailed the breakthrough as one more step towards growing safer pig organs and said it would revive interest in xenotransplantation – transplants across species – that has languished in the doldrums for 15 years. During the mid-1990s, Imutran, a small biotechnology company in Cambridge became the first in the world to transplant pig's hearts into monkeys and keep them alive, demonstrating that cross-species transplantation was possible. The pigs were genetically modified to overcome the primary immunological hurdle known as “hyper acute rejection” which normally causes an organ transplanted into a different species to turn black and die within minutes.

However, the secondary immune response known as “acute vascular rejection” has proved much more difficult to overcome. With the development of Crispr, researchers now face the task of identifying the many other molecules in pig cells that cause humans to reject them and then knocking the gene for each out in a way that doesn't kill the pig. Professor Church claims to have a list of the molecules and is working on finding ways of using Crispr and other methods to disable them.

While research on pigs proceeds, an alternative source of organs is being sought – in the laboratory. Kidneys or livers grown from a patient's own stem cells would not face the same problems of rejection and viral transmission. Brain cells are already grown in the laboratory for transplant into patients with Parkinson's disease. Growing solid organs poses greater challenges, but there is progress here, too.

Last month, Japanese researchers reported that they had successfully grown a kidney and bladder in the laboratory and transplanted them into a pig, where the organs continued functioning for eight weeks. UK researchers described the advance as “an interesting step forward”, but said a human transplant involving a lab-grown organ was still years away. In a second lab-based approach, scientists have stripped old organs unsuitable for transplant of their cells to leave a scaffold of fibrous tissue. The stripped-down scaffold is then regrown into a functioning organ using the patient's own stem cells – a quicker and simpler process than growing a solid organ from scratch.

The technique has been used to grow a replacement trachea which has been successfully transplanted into humans. Kidneys, hearts and lungs, which are more complex organs, have also been grown in this way, but the technique is not yet advanced enough to allow them to be used in humans.

On the success of these twin strategies – animal and lab-grown transplants – rest the hopes of thousands of potential patients, their families and their doctors who are desperate for any remedy that shows promise. As the organ shortage worsens, the pressure for solutions will increase. But for Ella and patients like her time is not on their side. Their chances will depend on adding donors to the register today and increasing the numbers from it who go on to donate the gift of life.

'The Gift of Life ', Channel 5, 10pm tomorrow

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