Gene Genie – Careful What You Wish For

The last 60 years or so have been splendid for those of us interested in genetics. It’s striking to think that it wasn’t really until 1952 that we came to universally agree that DNA was the heritable material rather than protein. This is only a year before the famous structure of the DNA double helix was uncovered. I would venture that almost everybody with any amount of post-infant-school education would be able to state that we inherit things from our parents via DNA. I would then go double or nothing that they could at least identify a picture of DNA.

Ooooh, look at those curves. Yeah!

DNA: This macro-molecule is why you're as ugly as both your parents , combined. Fact.

It is easy to forget that molecular genetics, in its modern sense, is a field that is younger than my mum. In that time the knowledge that won Nobel prizes has become ubiquitous. I was taught what DNA  stood for at the age of 11 in school (deoxyribonucleic acid, just in case you wanted to test me). Our classroom had one of those molecular models of DNA. Hell, if you don’t know anything about DNA from school, chances are you’ve picked up at least something from Jurassic Park or CSI.

I started my degree in Genetics back in 2000 and it is astounding how far the science come even in this short time. We have, of course, mapped the genomes of multiple organisms, which you can browse to your leisure. Molecular biology is one of those branches of science that is having an increasingly pervasive impact on life, and most people have strong opinions on the issues that are raised (i.e. GM foods, cloning etc.).

Hello. We have the same genome.

Oh noes! Clones! - An example of an ethical issue.

However, I think one of the biggest impacts yet to be felt as a result of the advances in molecular biology will be personalised medicine. The concept of personalised medicine has been bandied around for a while and essentially does (or will do) exactly what it says on the tin. Just as a brief summary, the idea is to be able to account for the obvious variability in people when dealing with their healthcare.

We all know that we differ in numerous ways. Tall, short, fat, thin, bald, hairy. French. Whatever your metric, we are not carbon copies of each other. As different as we are in obvious ways, there is also a vast amount of variation in less obvious ways. People respond to diseases differently. This may be down to innate differences in your immune system. Perhaps you have a variation of a single protein, which makes you resistant to HIV. The point is, as different we all appear by eye, we all are potentially as divergent in our response to disease. Just because we wear the same label for our disease does not mean the disease is affecting us in the same way.

Tissue Microarray

A tissue microarray can show dramatic differences between different patients suffering the same disease in the same tissue.

With the massive advances in genetics technologies we are entering an age where we can interrogate people’s genomes relatively quickly and cheaply (and this trend will continue from where we are today). This has massive potential in allowing us to tailor medical and pharmaceutical care towards individual patients which would lead to much more effective treatment regimes.

However, as always in life, there is a side to this that we should be wary of. Our ability to read the genome has accelerated beyond our ability to deeply understand the complexity it represents. That, in itself, is not necessarily a problem. It just means that as our theoretical knowledge catches up, the technology will already be there to allow us to continue understanding what the genome is and how, precisely, it operates. Instead, the problems arise when we pretend to understand it better than we do.

Moving on a bit from personalised medicine of the future, I am talking about personal genetic testing that is now available. I was going to link to one of the companies that offer the service but I have such deep ethical problems with it that I can’t quite bring myself to do it. Instead, look at this link to a cute dog. The most crucial point to make is that it is very hard to interpret what genetic analysis tells you about your actual risk of getting disease. Before direct-to-consumer genetic testing takes a big hold I think it is absolutely essential for people to understand this.

Relatively few diseases are the direct result of a single gene mutation. Instead, most diseases are multifactorial in their causes, arising from a combination of (potentially) numerous genetic factors as well as environmental factors. Even for researchers who spend their lives combing through genetic linkage data and calculating Risk Ratios it is no easy matter to interpret this data. More often than not, a mutation of one gene needs to be complimented by any number of other genes carrying mutations, as well as environmental factors. If you consider how complex the pathways tend to be in “running” your body, it gives you a better appreciation of how many factors can combine to cause any specific problem. A perfect example of this are the metabolic pathways with their sprawling networks and feedback loops.

Then we get to the question of what does risk even mean? If mutation A in gene Z doubles your risk of schizophrenia, what is that information telling you? Well if it increases your risk from a 40% probability to an 80% probability of developing the disorder, then that is a significant thing to know. If it increases your risk from a 0.25% probability to a 0.5% probability then you’re only talking, in real terms, about a 0.25% increase in your probability of developing schizophrenia (of course these are just figures I plucked from the air). The point is, it becomes incredibly difficult to make a balanced assessment of what this information is really telling you.

And yet, there are is an increasing marketing of personal genetic testing as some kind of crystal ball that will give you accurate knowledge of your future health. It won’t. In some cases it may tell you that you have a significant risk for something and there may be something you can do to reduce the risk. In some cases it may tell you that you are probably doomed, and there’s nothing you can do about. Great, now what? But mostly it won’t be able to tell you anything particularly coherent. But it might be able to panic you.

At our current level of understanding, we should be very careful about expecting too much from genetic testing. The knowledge simply isn’t there. And I certainly dread people facing discrimination in jobs and insurance because they’ve had their crystal balls rubbed up wrong by an insurance salesman.


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