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CNIO researchers take part in the most comprehensive personalized medicine study performed to date

The Spanish National Cancer Research Centre (CNIO) routinely runs such tests on samples sent in from all over Spain. But analysing genes is just the first step towards a truly personalised medicine. And researchers are exploring new ways to analyse what goes on in each organism at a molecular scale: the genes that are being read or transcribed; the proteins being synthesised; the antibodies circulating through the bloodstream; and the length of the telomeres capping its chromosomes.

The goal is not to measure a determined set of proteins, as in standard blood tests, but all the thousands of proteins that the body expresses at any given moment.

The next question is whether it is feasible to extract useful medical information from this vast outpouring of data and, if not now, whether it may be in the future. And it is here that the group led by Michael Snyder, Director of the Center for Genomics and Personalised Medicine at Stanford University (United States) is directing its efforts, in collaboration with CNIO researchers and the company LifeLength a CNIO spin-off.

"Currently states of health and illness are measured through a limited number of tests, which analyse a small number of relevant markers", write the authors in the March 16 edition of Cell. "But with new technologies we are now able to analyse a hundred thousand molecular components".

To find out whether these analyses can contribute something useful, Snyder himself decided to take the test. First, his genome was subject to detailed scrutiny. And what showed up were a moderately high risk of suffering coronary disease and a significantly high risk of developing hypertriglyceridaemia, diabetes and basal cell carcinoma a kind of skin cancer that has a high cure rate if treated in time.

A large number of short telomeres

He was also found to have a mutation in the telomerase gene, the enzyme which stops telomeres from shortening each time a cell divides. Telomeres are structures protecting the end of chromosomes, and their length is a measure of cells' biological age: as a rule, the cells of older organisms have shorter telomeres, while short telomeres are also associated with diabetes and other disorders.

The mutation detected in the telomerase gene is linked to a grave condition known as aplastic anaemia. Snyder does not have it. But Mara Blasco, of the CNIO, and Mercedes Gallardo, who works in Blasco's lab and collaborates with LifeLength, have measured the length of his telomeres and found that he has more short telomeres than is normal for a man of his age.

The team also documented Snyders transcriptome the genes that are actually being read; the levels of over 6,000 proteins in his body; the tens of thousands of compounds derived from the metabolism; and the antibodies present.

These analyses were repeated on some fifteen occasions in the space of a year and a half, making over three billion measurements in all. An unsought bonus was the chance to observe how a viral infection showed up in the results.

Snyder, in effect, contracted two mild viral infections in the data-gathering period, which left their molecular signature in the analyses. Perhaps the most striking observation was that, during one such infection, his blood glucose levels began to approach those of a diabetes sufferer, whereas before they had been normal, despite his genetic risk.

Just the beginning

For CNIO Director Maria Blasco, this study shows that diseases are a product of an individuals genetic profile as well as interaction with the environment. So far we know little about this correlation, while the use of human genome information to prevent and treat disease is still clearly in its infancy. But what we can see the tip of the iceberg is fascinating stuff.

Blasco and Gallardo concur that it would be premature to subject all patients to the battery of tests run on Snyder, although both believe it will happen in the future. From birth, we will all know what risk we have for developing certain conditions and can take steps to prevent it.

"In the long run, these tests will pay for themselves, because they will allow us to select a treatment for each patient that is truly effective and has fewer side effects", Gallardo adds. That is the goal of personalised medicine.

Snyder himself has no regrets: "It is great to have all this information [about oneself]. My eating habits are now completely different, and I ride my bike twice as much as before", he concludes.

Contact: juanj.gomez
Centro Nacional de Investigaciones Oncologicas (CNIO)

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