June 22, 2021

I, Science

The science magazine of Imperial College

This article is taken from the Spring 2012 issue of I, Science.

Jo Poole asks whether humans really can be repaired like machines.

It is true that however well we look after our health, from diet and exercise to vaccination, all organisms are subject to progressive changes. These arise via both extrinsic devices such as radiation and toxic chemicals, and intrinsic factors like the chemical stability of component molecules and the organisms themselves. Frankly, we are designed to die; it ensures that the best genes survive and controls competition for food and resources.

In otherwise healthy individuals, the final common road to dying is organ failure. Like machine parts they wear out, losing their youthful ability to repair. Then there are the more acute organ changes that precipitate death, such as trauma. In end-stage illness the only curative measure is transplant.

Mentioned in texts over 2000 years ago, transplants are surprisingly ancient. However, the first successful transplant was a cornea in 1905. The next – kidneys between identical twins – was fifty years later. The issue of rejection was first addressed in the 1940s and sufficient immuno-suppressants discovered in the 1970s. In the intervening years hundreds of transplants were carried out, but all perished in the post-transplant days and months.

The first successful heart-lung transplant was in 1981 and the field has grown exponentially since, including the live birth of a baby from a transplanted ovary in 2008 and a full face transplant in 2010. However, donor-transplants will never be suitable as large-scale therapy: donors are too few and the complications of immuno-suppression severe.

As Leland Kaiser predicted in 1992, “a future form of medicine that will interrupt chronic disease and repair or replace failing organ systems” is now coming to pass. Regenerative medicine based on stem cell research and tissue engineering is essentially building new body parts from scratch. Since the new parts have been genetically tailored to match the recipient, problems with rejection will be minimal. This technology is already being used in clinic.

Normal skin and tissue consists of cells embedded in a network of different fibres and chemicals including growth factors and signalling molecules. One such molecule is heparan sulphate, which has been used to help seal defects that cause herniation and promote regeneration of muscle chunks lost through trauma. The simple addition of heparan sulphate over wounds dramatically improves healing.

If cells are the various musicians in an orchestra, the extracellular matrix (ECM) is a bevy of conductors organising them into glorious symphonies. For many years research has focussed on stem cells when the real magic lies in the matrix between.

Since discovering the power of this matrix, tissue engineering has exploded. In one case, a donor windpipe was cleansed of cells leaving the scaffold matrix behind, which was then seeded with stem cells from a young boy. The cells adhered and differentiated into tracheal tissue, and the whole complex was transplanted into the boy where subsequent biopsies demonstrated new blood vessels had entered and nourished the transplant. No rejection took place since ECM contains no immune markers. Further to this, pig bladder matrices seeded with stem cells have been successfully used in moulds to produce artificial bladders subsequently used in humans.

Some of the most exciting prospects in organ replacement are burgeoning alongside the advent of 3D printing; ECM and different cell types can be loaded into cartridges and printed onto any mould. Beating rodent hearts have been produced this way and while the technology is new it holds tangible potential.

However, medicine is perhaps the most ethically controversial fields of science because its remit includes life, death and everything in between. It would be fantastic to hand a twenty-year-old stab victim new lungs, or give a young woman with polycystic ovaries a new chance at conception. But would we give a ninety year old with heart failure a new heart? They’ve paid their taxes. A further ninety years of incontinence would be untenable, so we could replace their bladder. Aching joints could be renewed. Hair transplants would erase grey hairs, collagen erase wrinkles, we could replace any organ that harboured cancer.

But no matter what level of medical proficiency society reaches, we simply cannot regrow the brain. It is not a mechanical tissue; its function relies solely on the connections made, wired up in response to real-time events. The brain could be compared to the London Underground, with stations as brain cells and lines as signals. To get from Wimbledon to Earl’s Court, one must pick a station on the District line. If Wimbledon were destroyed and rebuilt, it would be useless without being plugged back in to this line. You could plug it into the Central line but that would confuse everyone, and in a brain of this age, the rest of the Underground is unwilling to cooperate.

Unfortunately for us, in the brain analogy, Wimbledon is connected to a few thousand different lines and by the time we’ve rebuilt that, Earl’s Court would disappear. If you consider how much disruption line closures have on the Underground, you should have some understanding of what happens to neural circuits in the aging brain. Thus we may well be able to extend life, but at what expense? Will we simply be making human dolls, beautiful mannequins with fading memories and reduced interaction and awareness? And if doctors can’t write “natural causes” on death certificates, what will they have to write instead – euthanasia?

Image: flickr | Cea.