Uncovering the origins of cancer in healthy skin

(Written by Iñigo Martincorena, Cancer Genome Project, Wellcome Trust Sanger Institute Cambridge, UK) 

In the year 2001, the sequence of the human genome was announced as a milestone in science history. This represented a nearly complete map of the common genetic information in all of us. The project had taken over 10 years, the work of thousands of scientists around the globe, and it had cost approximately 3,000 million euros. This huge effort marked the beginning of a genomic revolution in biology.

Although it provided an unprecedented wealth of information, a single reference sequence for all humans contained little information on what makes each of us different or on the basis of genetic diseases. Since then, however, sequencing technologies have evolved dramatically. Nowadays, a person can be sequenced in a few days for less than 1,000 euros, and the cost continues to drop rapidly. This has allowed us to go from a single reference human genome to sequencing many thousands of people, unravelling the basis of many diseases and bringing us much closer to an era of personalised genomics in the clinic.

A field that has benefited enormously from the boom of sequencing technologies is cancer research. Cancer is largely caused by mutations that accumulate in our cells throughout life, which make every tumour unique. Genome sequencing can be used to catalogue the entire list of mutations in a cancer, providing a detailed understanding of the basis of any given tumour. The first genome of a cancer was sequenced in 2009 at the Sanger Institute (Cambridge, United Kingdom), where I work as a postdoctoral researcher. Just 6 years later, over 10,000 cancers have been sequenced throughout the world, providing a detailed catalogue of the genes altered across a wide range of cancer types. And this number is predicted to increase to several hundred thousand in the next few years. This is proving to be an invaluable resource for cancer research and, as we continue to learn how to use this vast information, it will significantly improve cancer diagnosis and therapy.

Cannabinoids: a new frontier for the treatment of Parkinson´s disease

The first evidences about the use of cannabis arise from the second millennium BC, when Assyrians used cannabis or, as they called it, “the drug that takes away the mind” for its psychoactive, mind-altering effects and for its medical properties. Since it was brought to the western world in the 18^th century, its use has been a source of controversy. Surprisingly, research on cannabis has advanced slowly. The major reason was the lack of knowledge about its basic chemistry. Unlike morphine and cocaine, which were isolated and used for research since the 19^th century,  the chemical structures of the psychoactive constituents of cannabis were not isolated until the 1960s. There are over 400 chemicals in cannabis, 80 of them unique to this plant. The exact chemical composition differs between plant species, the parts of the plant and growing conditions. Once the chemistry of the plant was elucidated and the psychoactive molecules identified, it was possible to find the bases of the endocannabinoid system, which is particularly relevant to functions associated with the central nervous system such as pain, mood or apetite. The elements of the endocannabinoid system are highly expressed in brain structures related to movement control, suggesting that they could also be involved in movement disorders such as Parkinson’s disease.

Genomic Editing à la carte

The recent decades have witnessed what has been named as a Genomic Revolution. The most recent discovery in this revolution is called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 (an RNA-guided endonuclease) system, a breakthrough new form of DNA editing. The system was originally discovered in bacteria and archae in the late 80’s. Microbiologists found in the genome of these organisms patterns of interspersed DNA whose function had remained elusive for many years. Several decades after, through sequencing of bacterial genomes, researchers discovered that these repeats were flanking DNA sequences of virus origin that the bacteria had incorporated into their chromosome. Moreover, these elements (CRISPR) were found to be in close proximity to genes that coded for proteins (Cas enzymes) involved in DNA cleavage and repair (Bolotin et al., Microbiology 2005; Mojica et al., J Mol Evol 2005; Pourcel at al., Microbiology 2005). Over the following years it was found that these viral sequences inserted at these specific loci constituted an immune memory that allowed bacteria fighting invading nucleic acids –such as virus- and blocking their propagation, and was the first evidence of an acquired immunity used by bacteria to adapt against foreign DNA. 

Meeting Mr. L

“Up above, how the bewitching eyes of the rose and the lips of the matinal carnation sparkle! How the maiden in the river laughs! And down below, the filter and the balance, the delicate chemistry of the liver, the storehouse of the subtle changes, no one sees or celebrates it, but, when it ages, or its mortar wastes away, the eyes of the rose are gone, the teeth of the carnation wilted and the maiden silent in the river”.

These are the words that Pablo Neruda, the famous poet, wrote to one of his biggest loves: The liver. That silent worker, faithful friend and mysterious organ that has so much to say about human health. Did you meet Mr L.?