The art of learning from microbes

ecoli-1184pxBy Antonio Polito

Do you remember Dolly, the sheep cloned 20 years ago? I was one of the many going on pilgrimage to visit her in its golden prison at the Roslin Institute, near Edinburgh. And like other reporters I was worried while talking with Dolly’s “father” Ian Wilmut, about practical and ethical implications of the breakthrough, which appeared huge at the time. Media were boiling with awe and outrage: is human cloning the next step? It would be evil or blessing? Are we playing God? 

Almost nothing happened. Nor man neither monkeys were cloned by nuclear transfer. Neither we got herds of cloned sheep. Anyway what would we make out of them? Then came the human genome sequencing,which at the beginning of the century looked like opening the book of life: despite some disappointment (just 30,000 genes counted in our species versus 18,000 in a worm) it heralded the new era of gene therapy. Again, in spite of many developments, disappointment went growing as new treatments remained scarce. Now it’s the turn of CRISPR, an almost untranslatable acronym referring to a brand new amazing  technique of genetic modification.  Excitement is high once more and hope easily becomes hype. In the last couple of years CRISPR has been celebrated by plenty of articles. A short selection from titles appeared in the international press include expressions such as “giant step”, the idea that “will change the world”, “the dawn of a new era”, “editing humanity”, “the genesis engine”, “the end of the world as we know it”. Are we getting wrong again?

Anna Meldolesi doesn’t hide that risk in her book but says that no, we are not overexcited because science goes in this way. “After the Peak of inflated expectations new discoveries plunge into the Trough of disillusionment. But fall doesn’t necessarily mean they are failures. Some technologies, the best ones, re-emerge, by setting realistic goals and slowly climbing the grade. Well placed hope looks like a hill which can be called the Slope of enlightenment”. No doubt CRISPR is still on the peak. It is a really revolutionary technology, borrowed from the immune system of microbes, which use it to fend off viruses. It works by programming a protein that is unleashed to search for a specific gene and then switches it on or off or correct the sequence when necessary. It can target many genes at the same time, radically shortening the time needed to carry out the experiments. Overall it is as precise as a “Swiss army knife provided with a positioning compass to explore the DNA, a vise to grip the double helix strands and scissors to cut the sequence”. Classic genetic engineering could only add the healthy copy of a gene where there was a faulty one in the hope that it would work, while now it is the faulty gene which is fixed. They call it editing, because it looks like the “find and replace” function in a word-processing program. Think of DNA as a book for children with typos. The phrase “twinkle, twinkle big star” should read “twinkle, twinkle little star.” Before CRISPR you could delete the adjective “big” or add the adjective “little”, but the result would have been confusing. CRISPR can find the word to be corrected (“big”), cut it off and replace it with the right one (“little”).

CRISPR can edit DNA letter by letter and its uses are limitless, including the genetic modification of human embryos. This taboo indeed has already been broken in China, the new scientific superpower. The goal was to edit the mutation responsible for β-thalassaemia by injecting single-cell fertilized human embryos. To be fair, results were not brilliant, as the technique was too immature, and crisprized children are still far away. But in the future embryos editing could allow genetic changes which are heritable and therefore virtually irreversible. Besides presenting new dilemmas CRISPR luckily offers also some help from the bioethics perspective. For example it is reviving hopes for xenotransplantation of humanized organs taken from animals, particularly pigs. Above all it could end the long-standing controversy on GM crops. CRISPR in fact can improve tomatoes or soybeans, rice or roses, without introducing DNA from other species and even help saving typical varieties. Edited products would not be transgenic and  the current restrictions would not make sense anymore.

Much will depend also on the press. Our job as editors will be critical to restart the conversation between science and society. “Names given to technologies affect the way they are perceived by the public”, Meldolesi writes. By saying “womb for rent”, for example, we stress that poor women are at risk of exploitation, while “surrogate motherhood” sounds more altruistic. What will happen to GMOs when their name will mean they have been improved instead than manipulated? Words count. It’s true, and this is why the title is the only part of this fascinating book which might deserve some criticism. As the author explains, man cannot create man. Humans can only work on what already exists in nature in order to improve it, as we are doing since we live on Earth. (Corriere della sera, 15/03/2017: picture: E.coli)

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