Less than a Virus

25 October, 2009

prion01We animals are susceptible to a bewildering array of infections. On the largest scale we can be infested by other animals. Worms, lice and other parasites can rather literally get under our skin and cause great harm. Smaller than the animals are bacterial infections. Single celled organisms that reproduce far more rapidly than our own cells, bacteria are often controlled by killing them with antibiotics, exploding their cell walls and leaving the remnants to be cleaned away by our immune system. Smaller again than bacteria are viruses. Not even truly alive, viruses are strands of DNA or RNA wrapped in a protein sheath. Unable to reproduce by themselves if left in the open they will often degrade into something that is harmless. But put them near one of our cells that they can attach onto and something else happens. They invade the host cell, often pulled in by the cell itself which sees the virus as something useful. Inside the cell the complex apparatus goes to work and ends up creating more of the virus, reproducing it as if it were part of the cell. Some viruses will then be pushed out of the cell which continues making more of the virus, in other cases the cell simply fills up with virus particles and explodes releasing the virus to continue infecting neighbouring cells.

Each of these three type of infection can be bad enough, but there is a fourth type the we have only begun to really understand since the 1980s. Creutzfeld-Jakob disease (CJD) is a rare inheritable disease that attacks the brain and is always fatal. It seems that a particular mutation can cause the malformed creation of prions, and these malformed prions cause damage to the brain. We all have prions in our brains, a protein called PrPC sits at the surface of our nerve cells and is believed to help with signalling or transmembrane transport. Those who have the defective gene for creating this protein end up with CJD instead. But this disease is not just inherited, it can be passed on as well. In Papua New Guinea people who took part in elaborate funeral rituals which included eating the brain of the deceased contracted a disease called Kuru which was strikingly similar to CJD. Experiments revealed that by injecting the malformed protein (PrPS) into an animal, the animal would develop a similar disease. So now an inheritable disorder was also caused by an infectious agent.

Comparisons of PrPC (the healthy protein we all have) and PrPS revealed something startling. There was no difference in the amino acid chain that made up these proteins, they were identical in makeup, but different in the way they folded. Proteins are made up of long strings of amino acids which fold into three-dimensional shapes, and these shapes determine their properties. By folding in a different way the PrPS becomes lethal. It also affects normal PrPC – for some reason the PrPC reforms itself into PrPS when it comes into contact with the PrPS. So by eating the brain of someone who has PrPS, or by having surgical instruments that have the PrPS on it stuck into you, you may end up having your normal proteins changed into something deadly.

In the UK in the 1980s, cattle were being destroyed to prevent the spread of BSE, another prion disease. In the 1990s a small number of people died of vCJD (a CJD variant) which was identified as having come from BSE infected beef. The ten people who died from vCJD were all very young (average age of 27) compared to classical CJD where the average age of onset is 65. This leads to the thought – what is the incubation period for vCJD? And how variable is it? In a worst case scenario, the people who have already died from vCJD represent an outlying anomaly and the full force of the disease has yet to reveal itself. The average length of time for CJD to express itself after someone is infected by contaminated surgical instruments is 15 years. It has been more than 15 years since the BSE was removed from the vast majority of british beef and the rate of vCJD has not spiked so we may be looking at a best case scenario where only a few hundred die of this disease.

In any case, proteins are not susceptible to our normal methods of sterilising (radiation and heat do not ‘kill’ them since they are not alive anyway) so unless we increase our understanding of prions we face a fatal disease, already within a number of people, with no hope of a cure.  Doctor’s advice: don’t go eating anyone’s brain. At least it wont spread that way.


Medical Ethics

23 October, 2009

medical-sharps-300x300Often in life we are faced with problems that we cannot solve ourselves. In many cases we can go to specialists who will be more able to analyse the problem and give us a solution. When your car breaks down and you take it to the garage to be repaired you trust that the service people know what they are doing, although you may get a second opinion. The same with getting a mortgage or any other major decision. When it comes to our health the decisions we make can be literally life or death and so we would like to arm ourselves with as much information as possible. Yet some decisions on, say, whether to try a treatment or not may require more information than we can absorb in a timely manner. Risk analysis can be difficult when weighing up, say, a 99% chance of chronic pain for the rest of your life versus a treatment that has a 2% chance of giving you cancer. In most countries with a modern health service, patient consent is a something that has to be explicitly gained. Some consent forms can be daunting though, and perhaps put patients off of getting treatment simply be being so dense with information. In many cases it is difficult to say whether one choice or the other would be best, and if a trained doctor can’t tell you, then what chance do non-specialists have? Of course as autonomous individuals it seems right that we should make our own medical decisions, but this can be dangerous.

Vaccinations are without a doubt one of the greatest life savers humanity has ever produced. Some are better than others though. Flu vaccines are variable in their effectiveness since each season’s shot is based on a subset of the viruses that are out in the wild. The flu shot will protect most people (after a couple of weeks) against that subset, but not against others that may be more widespread than predicted. In addition many of the most vulnerable people cannot create the antibodies that the flu shot should allow them to generate. Herd immunity is the best protection for the elderly, that is, if everyone was to get the flu shot there would be less flu going around and less of a chance for any individual to catch it. Most countries deem the expense of giving everyone the flu shot every year to be too high compared to the benefits of reduced mortality. This may be the sensible choice, but it is arguable.

Other diseases are much more troublesome. The measles vaccine is far more effective and only in rare cases will someone not get immunity from taking the vaccine. But such people exist, they take the vaccine, fail to develop immunity and don’t get measles simply because there isn’t that much of the disease around since everyone else took the shot. But what about when people opt out? By not getting the vaccine and allowing yourself (more likely your child) to get the disease you are increasing the chance of those non-immune people getting the disease as well. Even though they did all that could be done to prevent it, by quirk of fate, poor genetics, they get no help from the vaccine, and no help from herd immunity. Should vaccines therefore be mandatory? Should this medical decision be taken out of our hands?

Broad powers are granted to medical staff in the cases of outbreaks of especially dangerous diseases. Indeed we would probably not want someone to make their own medical decisions if they had been infected with Ebola and wanted to leave the isolation unit. It is not all or nothing, and an accommodation must be reached between, for example, the Human Right of Vaccination (as described by Mary Robinson) and the Human Right of freedom to do to our own bodies what we wish.

The ethics of testing drugs is also fraught with difficult, arguable choices. There are a large number of new treatments available now that have never been tested on pregnant women. This is entirely understandable, since who would risk unknown harm to their unborn child? Yet the result of this is that many conditions have treatments that cannot be given to people when they are pregnant simply because we don’t know the effect, and indeed probably never will. For some diseases, such as AIDS, it is often difficult to get people to try new drugs since the existing treatments are a ‘gold standard’ and work very well. Sure the new drug may be even better, but is it ethical to ask people to risk their lives with something that may be no better, or even worse than placebo, when there is an available, and worthwhile treatment? In all cases, whether searching for new treatments and cures, or even administering the existing ones, ethics plays a large part in the medical world.