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Interview
Neil Stokes - 5 February 2017 2.00 h

On the grammar of DNA

- Neil Stokes
Why is Cat­alo­nia so big in bio­med­i­cine?
It's out of pro­por­tion with the size of the coun­try. This in part is due to the long tra­di­tion of busi­ness, but also to the long tra­di­tion in med­i­cine. There have been many rel­e­vant doc­tors from here from dif­fer­ent decades. And this has cre­ated a pool of bio­med­ical sci­en­tists. It is also im­por­tant that in the past 15 years, all gov­ern­ments have sup­ported sci­ence.
Does Barcelona's rep­u­ta­tion as a cen­tre for bio­med­i­cine re­flect the fund­ing?
There has been sig­nif­i­cant in­vest­ment in the past 15 years, and it has at­tracted tal­ent from abroad. And this has cre­ated extra value.
What is epi­ge­net­ics?
Peo­ple know about ge­net­ics, that it re­lates to DNA – the book of life. But ge­net­ics is just the first chap­ter of the book and there are oth­ers. Imag­ine that ge­net­ics is as an al­pha­bet, well epi­ge­net­ics is the spelling and gram­mar; it gives you the pro­nun­ci­a­tion, the dif­fer­ent ac­cents, and this is chem­i­cal mod­i­fi­ca­tions. For ex­am­ple, a brain cell has the same ge­net­ics as a cell from the gut, but the func­tions are dif­fer­ent. This is be­cause the chem­i­cal mod­i­fi­ca­tions are com­pletely dif­fer­ent. All of these chem­i­cal mod­i­fi­ca­tions are epi­ge­net­ics.
We al­ways think of genes as un­chang­ing?
Until re­cently we thought you were stuck with your genes, that you are con­demned to live with that DNA. But this is not com­pletely true; per­haps only 10% of peo­ple have a strong ge­netic preva­lence to a dis­ease as­so­ci­ated with their DNA. For the other 90% there is the op­por­tu­nity for dy­namic and plas­tic changes in their DNA, and some of these can be re­lated to en­vi­ron­men­tal fac­tors. So epi­ge­net­ics is a trans­la­tor be­tween our en­vi­ron­ment and our cells, which can be mod­i­fied. But it is a sub­tle and slight mod­i­fi­ca­tion that gives you more or less ex­pres­sion of a pro­tein of a gene.
How do you iso­late these changes?
Let me give you an ex­am­ple, about iden­tity. We know there are dif­fer­ent human pop­u­la­tions, ac­cord­ing to epi­ge­net­ics, and this is be­cause they have adapted to live in a par­tic­u­lar en­vi­ron­ment. It might be they live in a coun­try where there is bac­te­ria that in­fects a lot of peo­ple and the DNA has adapted to sur­vive there. So we study the peo­ple in that coun­try and peo­ple in other coun­tries and com­pare their epi­ge­net­ics and look for the dif­fer­ence. Then we can de­ci­pher the dif­fer­ence.
Why the focus on can­cer?
Epi­ge­net­ics has an im­pact on health as a whole, on lifes­pan, on how fast we age. But can­cer is the tip of the ice­berg, be­cause it is easy to study. But we are now re­al­is­ing there is a rel­e­vance out­side can­cer. For ex­am­ple, in Alzheimer's dis­ease or in car­dio­vas­cu­lar dis­or­ders. It is broad and af­fects many tis­sues. For ex­am­ple, in neu­ro­gen­er­a­tion we are re­al­is­ing that the cor­tex of peo­ple with de­men­tia are un­der­go­ing epi­ge­netic de­fects, and this is im­por­tant be­cause we can cure 60% of can­cer pa­tients but we can't cure pa­tients with de­men­tia.
What are you re­search­ing at the mo­ment?
We have a broad in­ter­est but a strong em­pha­sis on can­cer. I'm very in­ter­ested in try­ing to look at the tu­mour, and from that knowl­edge gained, defin­ing a ther­apy for that pa­tient, which is more per­son­alised. Until now all pa­tients at the same stage of the dis­ease re­ceive sim­i­lar drugs, but now we have this em­pha­sis on pro­vid­ing a more per­son­alised can­cer treat­ment and this is what is called pre­ci­sion can­cer med­i­cine. And epi­ge­net­ics can con­tribute to that. It can also con­tribute to find­ing out why a tu­mour is some­times sen­si­tive to a par­tic­u­lar drug, dis­ap­pears and then after a cou­ple of years reap­pears. And when the tu­mour reap­pears it is now re­sis­tant to the first drug. Some­thing has changed, and this change most of the time is due to epi­ge­net­ics, be­cause this is a very plas­tic change – ge­net­ics is very sta­tic and epi­ge­net­ics is very plas­tic. We also have an in­ter­est in dis­eases called Rett syn­drome, which is a neuro-de­vel­op­men­tal dis­ease and is the sec­ond cause of men­tal im­pair­ment in women.
If epi­ge­net­ics is about changes due to ex­ter­nal fac­tors, is the best ther­apy to change those fac­tors?
This is true of all med­i­cine; the best treat­ment is to avoid the dis­ease. Pre­ven­tion is bet­ter for every­one and saves a lot of money. I say it is eas­ier to change cells than peo­ple. There are many en­vi­ron­men­tal fac­tors we can at­tack. For ex­am­ple, smok­ing, which is re­spon­si­ble for one out of every three tu­mours in the world. And it's not only lungs, but also the head and neck, the tongue, the throat, even the blad­der. Why the blad­der when it is so far away from the smok­ing? Be­cause it is where the tox­ins are elim­i­nated from the body. Ra­di­a­tion is an­other. It is clear that ex­po­sure to UV light is in­volved in the de­vel­op­ment of melanoma, for ex­am­ple, and it is clear that a high up­take of sugar is in­volved in di­a­betic dis­or­ders.
Dr Manel Esteller. Every Monday, English Hour airs the interview series Going Native. This time Neil talks to the biomedical researcher in the field of epigenetics at Bellvitge, Dr Manel Esteller.
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Neil Stokes
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