The genetic revolution has finally infiltrated the high street. Superdrug has become the first retailer in the world to sell a DNA testing kit.
Devised by California’s 23andMe, the kit will cost you £124.99 and will reveal your genetic risk of developing Alzheimer’s, Parkinson’s and forty-three other inherited conditions such as cystic fibrosis and sickle cell anaemia. You will also learn something about your sensitivity to twelve different drugs.
Last week I pottered down to Oxford’s Museum of Natural History, to a laboratory in the vaults of this famous institution, below the dinosaurs, the Dodo and the fossils. I was attending a DNA workshop that would give me a clear picture of certain of my genetic traits.
I attended this workshop because an understanding of DNA is absolutely fundamental to biotechnology. After all, improving understanding of DNA is the single key driver of the biotech revolution that is under way. We are dismantling living things down to the very DNA that instructs their workings, we are analysing the results and we are manipulating them to our advantage. From genetically modified plants to the genetic modification of our own immune system, DNA is the key.
What does Christmas lunch tell us about the human genome?
Do you like Brussel sprouts? I do. When Christmas comes around you can give me as many as you like. I have never understood why others have such an aversion to this tasty vegetable. It turns out that the answer is genetic.
I started the DNA workshop by placing a small strip of paper on my tongue. It looked harmless and tasted of nothing. But other members of the workshop spat it out immediately. They found it disgusting.
They had a strong adverse reaction to a chemical that was infused in the paper. This chemical is phenylthiocarbamide, the same chemical that is found in sprouts.
Let’s go back to basics. Each cell in your body contains a full set of DNA, which you inherit from your mother and father. ‘Haploid’ cells contain 3 billion base pairs from one or other parent. But most cells are ‘diploid’, meaning that they contain the full set from both parents, a total of 6 billion base pairs. Each base is either adenine, cytosine, guanine or thymine, and in the double helix each base is paired – A with T and C with G.
Somewhere along this sequence of three billion pairs is a section of about one thousand that constitutes a gene called TAS2R38. This instructs a cell to manufacture a particular protein that is found on the tongue and influences our sense of taste.
If you have the full set of a thousand bases, you should have a strong sense of taste. But if there is a mutation in the sequence – perhaps you have a C instead of a G – then this will change the instructions relating to the production of protein, and you will be a ‘non-taster.’
I could barely taste the phenylthiocarbamide. I was a ‘non-taster’. How could I prove that this was genetic?
Applying the technology behind DNA sequencing
After tasting the paper strip, I took a swig of salty water, swilled it around my mouth and spat it back out. The water now contained a few million cells from the inside of my cheek. This was spun around a centrifuge machine at high speed until the cheek cells had amalgamated into a little pellet at the bottom of the vial.
Next I mixed the cells with some chelex beads; these beads effectively crack open the cells, revealing their DNA. DNA is of course very small, so small in fact that we can only see it at all if we have billions of copies. Thanks to an eccentric Californian, Kary Mullis, we have an extraordinarily efficient way of making copies. This is called Polymerase Chain Reaction – PCR for short.
I added some man-made DNA ‘primers’ to my DNA and placed the vial in a small machine. The primers locate the start and finish of DNA sequences that are of interest, and then pull the double helix apart. The separated strands then make copies of themselves. If you repeat this sequence 35 times, you produce 34 billion copies of the relevant gene.
So, I had billions of copies of my TAS2R38 gene. Next I had to discover whether I had a mutation in that gene. To do that I needed a restriction enzyme and a process called gel electrophoresis. A restriction enzyme – in this case called HeaIII – automatically recognises a pre-defined section of DNA and makes a cut at that point. For example, if it sees CCGG it will make a cut after that sequence. But if a mutation has turned that sequence into CCCG, then it will not make a cut.
That is the crucial point. We would know if CCGG were present because we would have two short, cut, sections of DNA. If CCGG were not present, the enzyme would not have cut the DNA, and so we would have one long section. To determine whether I had short sections or long sections I used a process called gel electrophoresis: the DNA was placed at the end of a gel which was then placed in a small bath. An electric current, was then run through the bath, attracting the DNA from one end to the other. Crucially, the shorter the section the further it would travel. The longer sections would encounter more resistance from the gel and travel more slowly.
We finished with something that looked like this:
The horizontal lines represent the DNA within a single gene. Each strand started at the top of the picture; you can see that some have moved further down than others. We can deduce that the sections that have travelled farthest are the shorter sections that had been snipped at the point of the CCGG bases.
The whole experiment took several hours and was a bit more complicated than I have described here. It was certainly a lot fiddlier. We used pipettes to manipulate minute quantities of cells and other agents. One slip of the hand and the whole experiment would have been ruined.
That, sadly, is what happened to me! While others in the group had a nice clear result that proved the correlation between their genes and their sense of taste, the movement of my DNA was almost indistinct!
That did not make the day any less enjoyable or educational. I learnt how scientists look for genetic flaws, and I learnt about inheritance. As I mentioned above, each person actually inherits two sets of DNA, one from his or her mother and one from his or her father. Both could be ‘strong tasters’ or ‘non-tasters’, or they could be one and the other. If both are the former then we will most likely also be strong tasters.
Now, an inherited aversion to Brussel sprouts is hardly a matter of life and death. But if the genes related to Huntington’s Disease that would be a serious matter and something that everyone would like to know as early as possible.
I learned a lot at this DNA workshop, but one point in particular stood out: this process is eminently scalable. In fact, the process is much better carried out by robust machinery than middle-aged journalists with shaky hands. It is this scalability that makes biotechnology so revolutionary. Rapid developments in gene sequencing and testing are helping scientists turn the natural world to human advantage. Crops are becoming more resilient and more productive. Medical treatment is becoming more efficient and more cost-effective. Genetic science is changing the world almost weekly; both patients and investors are feeling the benefits.