Transplantation - a Summary Content from the guide to life, the universe and everything

Transplantation - a Summary

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Transplantation is now a common procedure in all developed countries, and has become as much a part of modern medicine as the stethoscope.

When you say the word 'transplant' to anyone, most people will think of the weeping family wrestling with the issue of whether to donate their child's organs for transplant after a tragic accident; the scenario publicised on programmes such as ER and Casualty. However, not all transplants are as dramatic as this, or involve the recently deceased.

Autograft

auto = own (as in autobiography)

This type of transplantation involves taking part of the patient's own tissue from one part of their body to replace damaged tissue in another area. The best example of this is skin grafts in burn victims. In this procedure, skin is commonly taken from the inner thigh to replace skin elsewhere, eg on the face.

It has the advantage of being homologous1 to the patient. Thus, the patient won't have to take immunosuppressive2 drugs, and won't suffer the consequences of rejection (see below for a definition). However, as you can imagine, it is very limited. You couldn't really do this with an internal organ.

Cadaveric Transplant

This is the best-known of all transplants. The donor is deceased, often young, with all their organs in good working order. It is also the most publicised, for the reasons outlined above.

This mode of transplantation is best for:

The major organs are, in fact, best obtained from this source; dialysis machines aren't nearly as good as the kidney, just as a mechanical heart pales against a good natural heart. Why is this method preferred? At the time of writing, the best is that made by nature; only the real thing will work as well as the real thing. The patient will thank you for sparing them the inconvenience of a dialysis machine, sticking needles into veins, and a strictly regulated diet.

However, it is not without its downside. As the organ in question is coming from a different body, all the blood and immune matching in the world will not stop the slow and dehabilitating process of rejection. To slow this process, the patient will have to take a lot of immunosuppressive drugs. Also, decisions have to made very quickly, both ethical and surgical ones. In the hurry, mistakes can be made. However, the major downside to this method occurs before the transplant gets to the person.

Supply and Demand

The major problem is that the demand for cadaveric organ transplants has risen, but the supply of good cadavers had largely remained static. This is due to a very good measure ie, the introduction of back-seat seat belts, and a massive education scheme for the wearing of crash/cycle helmets. Before this, an RTA (Road Traffic Accident) was a tragic yet sure-fire way of getting a young and healthy set of organs. Hence many needless deaths have been prevented, with the unfortunate downside of reducing the chances of others to live. Recently, several organ retaining scandals have led to a drop in organ donation. The waiting lists have sky-rocketed, and there is very little that the patients can do but wait, and hope.

The Living Donor

This is, like the cadaveric donor, a common plot not only in hospital dramas, but soap-operas too: the weeping relative makes the near-ultimate sacrifice by donating, almost always, a kidney. However, this is not as clich├ęd as it seems.

As said in the previous section, there is a lack of cadaveric organs. Only a few of those may be viable for transplantation, as some will be damaged. Even the few which are viable will have to be cross-matched3 to reduce the chances of rejection. As the cadaveric donor is of a different genetic make-up to the patient, there will always be the problem of rejection, no matter how close the match is. If the donor is a relative, the problem is reduced.

The Theory

The best donated organ is one which is genetically identical to the recipient. This could either be one from an identical twin, or theoretically a clone. However, if the patient is not a twin, the second best organ is that from a blood sibling. This is because you will share half your genetic make-up with your sibling. Failing that, a parent or another blood relative will do. The running theme is that within your close circle of relatives, there is a similar genetic make-up. Thus on cross-matching, it will be as similar as you are likely to get. It may not be as close a similarity as a twin, but it is much better than a person to whom you are not related. This all adds up to a reduction in the chances of rejection and the prolonged life of the recipient. That is, if you are indeed matched.

Currently, living donors can donate:

  • Bone marrow
  • Liver lobes
  • Lung lobes4
  • Kidney

It may sound fantastic, but there are problems.

The Problems

If the donated organ in question is bone marrow, then should there be problems with the bone marrow of the donor, at least it is just a few cells and not all the bone marrow which is faulty. However, if it is a kidney, then the donor will be left with only one. Your body can cope quite well with just one kidney, but should that pack in, the donor is left with a real problem: they would have to go on dialysis, and in turn, on the organ recipient waiting list. Not particularly nice, as you can imagine.

There is a more sinister problem, and that is of coercion. Let's look at a hypothetical scenario.

A favourite son from a close-knit family requires a kidney transplant, yet can't be found a suitable match on the cadaveric organ register. His less favoured sister is about as close a match as you can find, but does not want to become a donor, because she fears she too may have kidney problems in the future.

On returning home, for the next week, she is put under immense psychological pressure to give her brother her kidney. She returns three days later, accompanied by her parents, to say she will be a donor. The atmosphere is noticeably tense.

Yes, this is indeed an exaggerated scene which could have come out of a hospital drama, but unfortunately, not an entirely unusual scenario. There may be some pressure on the donor, and they may have not volunteered of their own accord. It is essential, from the doctor's point of view, that they have done this of their own free will, and not out of pressure from the family, no matter how strong their feelings are.

Xenotransplantation

xeno = foreign (as in xenophobia - fear of the foreign)

This is the transplantation of animal organs into human recipients. The medical profession wouldn't usually be considering this, but with the large number of people currently on organ reception lists, doctors are desperate to pursue all routes to improve quality of life. This is one thought.

The Theory

There is potentially an inexhaustible supply of organs here and there is the opportunity for well-planned, unhurried operations, where the donor can be selected at length. Primate organs have been shown to survive in human recipients; outside our own species, they are our closest relatives. Xenotransplantation is already in use: pig heart valves are been used to replace worn-out human ones in people suffering from valve disease. This procedure has a good success rate. Pig organs can also be manipulated at the genetic level to ensure that they 'appear human' to the human immune system, reducing the degree of rejection.

There are still some issues with the theory which make it a less than perfect solution.

Problems with the Theory

With primate transplantation, there will still be an organ shortage. This is due to the slow breeding rate, similar to the human breeding rate of nine months. The breeding rate with pigs is relatively fast, so if you get that one right, the organ shortage can be reduced. However, as the pig is not really a close relative, rejection will be severe and fatal.

There are additional problems concerning infection. It has been shown that some viruses present in pig organs can infect human cells in vitro5.

Breeding animals for the sole purpose of human advancement in medical techniques and hence improving quality of life has always been at odds with the opinions held by animal rights groups. The quality of life of the animal donor in question would be in theory next to nothing; being kept in cages etc, and the principle that its rights have been taken away from it, ie the right to live out its natural life without fear of torture or impending death, which is so taken for granted by humans. There is an additional ethical worry here: if one can so easily breed animals for this purpose, it may be one step away from doing the same with humans.

A final problem. People tend not to like the idea of having an animal transplant in them. This is otherwise known as the 'yuck factor'.

Stem Cell Transplantation

Stem cells are self-renewing cells, ie immortal6, and are able to become any tissue at all. Why are we interested in these? With an ever ageing population, the number of people who have diseases associated with increased age, such as Alzheimer's and Parkinson's Disease7 have increased. If we can replace these cells, then we can reverse the disease. This may sound far off, but it is the method currently used in the treatment of leukaemia: the bone marrow transplant.

An Example - Bone Marrow Transplantation

Bone marrow contains a type of stem cell called a haemopoietic stem cell, which can become any aspect of blood: red blood cells, white blood cells etc. In leukaemia, there are too many white cells due to a problem in one cell of the patient's own bone marrow. To reverse this, healthy bone marrow can be injected into the patient's own, with the intention of this healthy tissue to grow and replace the patient's own unhealthy bone marrow cells. Hopefully the graft will destroy the host's damaged cells. Unfortunately, sometimes there can be a 'graft vs host reaction', where the host's faulty cells are not destroyed, but instead attack the graft. This is a type of rejection, and is again very, very bad for the patient. To prevent this, doctors try immunosuppression.

This type of stem cell transplantation is relatively easy in bone marrow, but a little bit more difficult in the brain. There are many stem cells in the bone marrow, whereas in the brain, they are few and far between. Therein lies the very big controversy.

Embryonic Stem Cell Transplantation

There was a time when you were nothing but a ball of cells, where all the cells were exactly the same, and had not yet become heart, lung or other specialised tissue. Now, with the technology available, artificial insemination8 of cells can occur and scientists can remove some cells when the embryo reaches that point. Then substances can be used such as growth factors to push the cell into becoming whatever tissue (or theoretically, organ) is required. These cells are called 'totipotent' cells.

The advantage is that as it is human, the chance of rejection is reduced. Also, using cloning technology, we can take one cell from the patient, and clone it, and wait until it gets to the ball of cells stage. Thus a perfect match for the patient who requires the tissue can be created. However, there is one very large problem.

The Ethical Question

This is essentially creating human life to destroy it. Your clone has the potential to become a human: living, breathing and walking among us, contributing to society like us, enjoying life, like us. Would we have the right to take that life away in the pursuit of prolonging another?

On the other hand, can we as a society stand by and let people die when we know that we have the technology to save them?

The infuriating thing about ethics is that there is no right or wrong answer. It may be best to let you come to your own conclusion on that issue. However, all is not lost for stem cell technology. There is one last method.

Pleuripotent Stem Cell Transplantation

So what makes this different from the totipotent stem cells? Well, pleuripotent stem cells are a step ahead of the totipotent stem cells; they can develop into any cell in a certain tissue, but not develop into any tissue cell. The best example of this is the haemopoietic stem cell found in bone marrow. It was thought that, as they were the next step along, they couldn't develop into anything other than components of blood.

The first inklings that bone marrow could turn into other tissues came when doctors took a sample of bone marrow from a man who had a liver transplant. On counting and imaging the chromosomes from the nuclei of the bone marrow, they found that some were genetically female. Which was a bit strange, they thought. On further investigation, they found out that the donated lobe of liver had come from a female donor. There seemed to be no other explanation: liver cells were becoming bone marrow cells.

Further evidence came when women going for liver biopsy were found to have male liver cells in their sample. Again, all feasible explanations like contamination of the slide or the wrong slide were excluded. Then it was found that they all had sons; not newly born sons, but older sons. What must have happened was that foetal pleuripotent cells, probably the haemopoietic ones, had crossed the placenta when the foetus was in the womb, not been recognised as foreign, settled in the developing liver, and then developed according to their environment. The surprising thing was that they had also survived for so long.

This blew apart the theory outlined above. It seemed that cells developed according to their environment, regardless of their stage of development. It also seemed totally feasible that, if pleuripotent liver cells could turn into bone marrow, then the pleuripotent bone marrow could likewise turn into liver, or for that matter, any organ. Also, bone marrow is easily found, and there are lots of haemopoietic stem cells about.

So in 2001, scientists from the Imperial Cancer Research Fund (UK) did exactly that, but with kidney. Unlike the liver, this doesn't repair itself after damage. It seemed the obvious choice to test this new theory. Again, female bone marrow was injected into the damaged kidney in a male patient. After some time, they took a biopsy - the removal of a small sample of tissue from the body - from the damaged area of the kidney, and it seemed that area was repairing itself. When checking the gender of the cells, it was found that some of the new kidney cells in the repaired area were indeed female. It seems possible to rebuild damaged organs which previously didn't have the ability to repair itself.

This, like embryonic stem cell technology, is still in early development at the time of writing. However, as the stem cells come from consenting adults, and not embryos, it bypasses the ethical and moral issues which so dog its more controversial relative. The hope is that the patient's own bone marrow can be injected into the damaged organ, which will repair itself, avoiding rejection.

Rejection

This occurs when the body's immune system doesn't recognise the transplant as part of itself, and attacks it with all its might. There are three types:

  • Hyperacute rejection - This is now not usually seen as a cross-match of the donor to the patient is done prior to surgery. The organ is dead within 20 minutes of transplanting it to the patient.

  • Acute rejection - This occurs within the first three months, when the differences in the donated organ and the recipient's tissue are recognised. This rejection is usually controlled using immunosuppressive drugs.

  • Chronic rejection - This is similar to acute rejection, made a lot worse by an increase in blood pressure. All recipients of cadaveric organs will succumb to this, which is why the average survival of those who have received an organ like this is still only ten years post-transplantation, even with immunosuppressive drugs.

1Having exactly the same genetic make-up, thus not posing a problem to the immune system.2These drugs 'dampen down' the immune system's attack response to foreign material. They are not without their problems. Not only do they have nasty side-effects, but they have to be taken for the rest of the patient's life.3This is a comparison of a small aspect of the donor's genetic make-up called Human Leucocyte Antigen (HLA for short) to the recipient's.4In human anatomy, the liver and the lung are both divided into several lobes, which can be removed without significant loss of the donor's quality of life.5A literal definition for this term is 'within glass'. This is the term for in the test tube, ie in the lab and not in vivo, ie within the body.6In this context, 'immortal' means that these cells have the ability to divide forever.7These are diseases which cause brain cells in areas controlling cognitive function and coordination of movement, respectively, to die prematurely. As brain cells regenerate at such a slow rate, the effect is that of degeneration of these functions.8Take a female egg, inject it with a male sperm in a petri dish to mimic conception.

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