The future of diagnostics is digital

The heart beats rhythmically, its muscles quivering, the bright red blood pulsing through its chambers. It appears vibrantly — queasily — alive. But this heart is not inside a human body. It is kept artificially beating by a state-of-the-art machine, the Organ Care System (OCS), which simulates the body’s functions and even re-oxygenates the blood — one of the latest extraordinary inventions set to revolutionise the landscape of organ transplantation.

The same system is being developed for lungs — which keeps them ‘breathing’ outside the body — and others will sustain livers and kidneys. Kept at body temperature, they are fed with blood and nutrients while their function is observed. The benefit is not just that doctors are able to assess their suitability for transplant, or that they can be preserved for longer (up to 12 hours) before being transplanted; the machines, research has shown, actually improve the quality of the organs.

The development is so exciting that the traditional ‘ice box’ approach to transporting organs may be obsolete within five years. In use since the 1960s, the process involves flushing donor organs with a specialist preservation solution and keeping them packed with ice at 4 C, which slows the rate at which cells deteriorate. But it needs updating because the demographic of organ donors has radically changed. Improvements in cardiovascular medicine, and the introduction of helmets for cyclists and motor bikers, means the pool of organ donors is now older, and more likely to have died from a range of co-morbidities. In short, organs are of poorer quality, and more likely to fail. Additionally, the process of transplantation causes progressive injury at every stage as cells die.

The answer, according to transplant experts, is threefold: improve the condition of the organs that are available, repair those that suffer injury, and preserve them better before transplant. Medical journal the Lancet last month called for more research to meet this goal. While some of the work remains science fiction, most is tantalisingly close.

André Simon, director of heart and lung transplant at the Royal Brompton and Harefield NHS Foundation Trust, uses the TransMedics’ OCS system to transplant every heart — 120 since 2015. He is working with Imperial College London to develop a cheaper alternative: OCS has cost an estimated £229 million so far to develop, and consumables amount to £30,000 per transplant.

‘The OCS is a brilliant system, but we have so many ideas it would be a crime if we didn’t use them,’ Mr Simon says. ‘We envisage a versatile system working like this for every organ, that’s affordable and adaptable. It could be the single most important thing to make a difference in organ transplantation in the UK.’

He adds: ‘The goal would be to have a heart that you have observed beating, and then you put it into some kind of storage, and you store it for a week. You can bank it so you have time to find the right patient.’

In Sweden, researchers revealed last month that they had transplanted a patient with a heart which had been preserved ‘in a deep sleep’ state at 8 C, using a blood-like solution containing high levels of potassium. This reduces cell activity and the organ’s need for oxygen, and could keep hearts outside the body potentially for days, in order to find the perfect recipient.

The OrganOx system, developed by Professor Peter Friend and Constantin Coussios at the University of Oxford, keeps the liver functioning at body temperature for up to 24 hours — but experimentally they have been stored for up to 48 hours and, in theory, could be kept significantly longer. The team is actively looking at developing its system for other organs.

‘The evidence we’ve come up with thus far suggests two things — you can make bad organs better, and you can make a better assessment of whether a high-risk organ could be transplantable or not,’ explained Prof Friend. There is increasing interest, too, in using the human body itself to preserve organs after the donor has died — a process called normothermic regional perfusion, or NRP.

Gabriel Oniscu, chairman of the Novel Technology in Organ Transplantation working party at NHS Blood and Transplant, and the clinical trials committee at the British Transplantation Society, said NRP had produced ‘spectacular’ results.

It involves isolating the abdominal cavity and perfusing organs within it with blood, keeping them oxygenated while tests are carried out to establish viability before the organ is removed and transplanted. ‘The results have been phenomenal,’ said Mr Oniscu. ‘Around 24 per cent of liver transplant patients may have to be re-listed for transplant or treatment because of scarring to the bile ducts. We’ve reduced that to zero, probably because this technology reconditions the organs. We’re expanding it to the heart.’

There is also, he says, the ‘tantalising prospect of gene therapy’. Scientists have been working on ways to delete faulty genes in organs which improves their liability for transport. The UK regulator, the Human Tissue Authority, is already examining the legal ramifications of such work — the major question being whether an organ that has been ‘edited’ can still be considered an organ or has become a ‘device’.

Elsewhere, interesting work to rebuild organs has had some success with rat hearts. Organs are stripped of their living cells and new, healthier cells are then built on the remaining scaffold.

Work is also continuing in the US on xenotransplantation — growing human organs within pigs, an animal version of the clones-for-organs dystopia imagined by Kazuo Ishiguro in his novel Never Let Me Go. A mouse pancreas has already been grown in a rat, and transplanted back into the mouse, ridding it of diabetes.

Artificial organs, too, could form part of this revolution. An artificial womb in Philadelphia, essentially a plastic bag filled with nutrient-rich ‘amniotic fluid’, has supported foetal lambs equivalent in age to 23-week-old babies, raising hopes that premature humans could also benefit.

These are headline-grabbing achievements. But quietly, in Oxford and elsewhere, another development could make a perhaps even more significant breakthrough. Transplant scientists and doctors are working to harness the body’s own immune system to prevent organ rejection after transplant. At the moment, patients need a lifetime of immunosuppressant drugs, which can lead to cancer and heart problems. It means some patients are not given transplants because of the risk.

But an international clinical trial on patients has shown that, by isolating the body’s own cells responsible for regulating the immune system and amplifying them, there may, in future, be no need for the drugs at all; or at least, a significantly reduced dose.

‘So far it’s been promising,’ said Prof Friend. ‘We’ve given the cells in combination with a slightly reduced load of conventional drugs. If it works, a lot of things will change — the whole threshold for transplant will change. It’s a huge hope, and potentially a game-changer.’

Mr Oniscu added: ‘Within five years, most of this organ preservation and enhancing technology will become standard. Progress has been phenomenal and there are clear indications of benefit. We’re living in a new revolution of transplantation — it’s a very exciting time for surgeons and patients.’