CRISPR Technology explained by Dr. Martínez Mojica

El impacto de la tecnología CRISPR en biomedicina.

Sesión científica celebrada en la sede de la Reial Acadèmia de Medicina de les Illes Balears el 9 de julio de 2019 a cargo del profesor Francisco Juan Martínez Mojica, microbiólogo, investigador y profesor español titular del Departamento de Fisiología, Genética y Microbiología de la Universidad de Alicante.

Genome editing: a potential weapon of mass destruction

The Patent Dispute Over Gene Editing Technologies: The Broad Institute, Inc. vs. The Regents of the University of California

Nobody could imagine two decades ago that a small part of wide range of bacteria's immune system could represent so much for genome editing. Known as CRISPR, clustered regularly interspaced short palindromic repeats, such mechanism can recognise and defend against viruses. The other part of the defense mechanism is a set of enzymes called Cas that can cut DNA and avoid the invasion of viruses. Mostly, these research was originated in Les Salines d'Alacant by Francisco Mojica a microbiologist.
As far as this is a natural process Dr. Mojica didn't show interest in patenting it. Now the row over patents is hot between UC Berkeley and the Broad Institute. I will skip details, you may find it in The Economist.
It seems that the fight is only to determine who was the first, and the Court will have to decide on March 9th. However, my question is: why is it still possible to file a patent over human nature?.
Meanwhile the public debate may be moved towards the use of such CRISPR technology for genome editing, and Science was publishing an article about the threat that misuse represents for human beings. Are we facing a new weapon of mass destruction?
Both issues, patents and bioethical implications are crucial at the moment. Former examples provide clear guidance of outcomes that should be avoided. Unfortunately, the race for the biggest size of the pie (billions of $) seems to be a priority over health and humanity.

CRISPR Nobel prize

 Genetic scissors: a tool for rewriting the code of life

GREAT NEWS! 

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2020 to

Emmanuelle Charpentier, Max Planck Unit for the Science of Pathogens, Berlin, Germany

Jennifer A. Doudna, University of California, Berkeley, USA

“for the development of a method for genome editing”

Popular information: Genetic scissors: a tool for rewriting the code of life (pdf)

Scientific Background: A tool for genome editing (pdf)

Unfortunately, the Royal Swedish Academy of Sciences has shown its ignorance about the real discovery of CRISPR. It happened in the '90s in Salines de Santa Pola by Dr. Martinez Mojica.

Genome editing: the game of biology is about to change

Hacking the Code of Life: How gene editing will rewrite our futures

The foundations of gene editing came about because a scientist in Alacant, Dr. Mojica started to find weird DNA sequences in some bacteria he was studying. After that Profs. Doudna and Charpentier and later Prof. Zhang translated initial findings into practice. Therefore it all started when a microbiologist studied the arms race between bacteria and viruses.
You'll find all these details in a book by Nessa Carey. If you want to understand in plain words what CRISPR is and what may represent for biology, then you have to read it.

The gene editing revolution is creating a technological toolkit that almost any half-decent scientist can lean into and find something useful. On the one hand, that should make us very excited. We can both solve problems and simply indulge our curiosity. But should it also make us worried? Using chisels and a mallet, Michelangelo created some of the most exquisite sculptures we have ever seen. But give the same heavy, sharp tools to someone else, and we can get a very different and much bloodier outcome.

But the same technology can also be used to alleviate human suffering, and if we are smart enough, lessen the impact that our heavy-footed species has on the only planet we know of in the entire universe that supports complex life. We cannot un-invent this technology, we probably can’t even control its spread. So what choice do we really have but to embrace it and use it well, to create a safer, more equal world for all?

Aturem els nadons de disseny

The Transformative, Alarming Power of Gene Editing. A rogue scientist showed that CRISPR gives humans the ability to transform ourselves. But should we? 

Aquest era el text d'una pancarta davant la reunió d'experts en genètica el març passat a Londres, a l'Institut Francis Crick: "Aturem els nadons de disseny". Era la segona vegada que es reunien genetistes després que a l'anterior reunió el 2018 on He Jiankui va mostrar un dels més grans disbarats recents de la ciència, l'edició genètica d'embrions per intentar eliminar l'HIV. Ho vaig explicar ja fa dies.

No el van deixar entrar. El 2022 ja va sortir de la presó i ara dirigeix l'Institut de Medicina Genètica de Wuhan, no m'he confós, és a "Wuhan", de trist record.

Els del New Yorker just ara han publicat un article magnífic on s'explica amb molts detalls tot plegat. M'ha interessat saber què havia passat amb els dos nens, que de fet després es va saber que eren tres.

From the moment the children’s existence was made public, scientists have clamored for information about their genetic health, amid dire warnings of likely abnormalities. Because JK’s data have never been published, experts have been left to pore over his short talk at the Hong Kong conference and an accompanying slide presentation, and to scrutinize his few statements. In one of his YouTube videos, he said that he had sequenced Lulu and Nana’s entire genome before implanting the embryos, and again after they were born. The results, he said, indicated that the procedure had worked safely, as intended.“No gene was changed except the one to prevent H.I.V. infection,” he said.

This was, at best, a gross oversimplification. In the Northern European variantof CCR5 deletion, thirty-two base pairs of DNA are missing from both thematernal and the paternal chromosomes. JK’s results didn’t match this standard.Instead, in one twin, he had created a novel mutation of thirteen base pairs—probably but not defi nitely enough to prevent an H.I.V. infection. The other twin had one mutated and one normal copy of the CCR5 gene, weakening the prospect of immunity.

Another serious concern is that both twins are likely genetically “mosaic,” made up of edited and unedited cells, which may mean that neither of them has any special resistance to H.I.V. at all. Kiran Musunuru, a prominent gene editor,argued that JK’s work was not a CRISPR breakthrough—it was “a graphic demonstration of attempted gene editing gone awry.”

Doncs això, a sobre de ser un disbarat ètic no va assolir el que pretenia, va ser un fracàs. Fa temps que tenia curiositat sobre això i és aquest article que m'ha permès entendre millor l'abast del problema que tenim davant nostre i no li fem prou cas.

En aquest blog he explicat en moltes ocasions diferents aspectes de CRISPR, que els del New Yorker la citen com la "tecnologia biològica més transformadora", i sabem que malgrat la controvèrsia en l'ús amb embrions en línia germinal, segueix avançant i ara ja tenim l'edició base i l'edició prime, que també es tradueix com edició de qualitat.

Enmig de l'article em trobo una sorpresa més. Resulta que hi ha un laboratori a Oregon que ha estat autoritzat per a investigar en edició genètica d'embrions humans, no només amb rebuig de fertilització in vitro. El dirigeix Shoukhrat Mitalipov, kazakh, i entre els investigadors trobo a Núria Martí Gutíerrez, valenciana, que és la responsable d'embriologia al laboratori. Ella explica en detall el procés d'edició d'embrions com si res. Diu l'article:

Martí Gutierrez moved the dish over to a larger microscope, equipped with pipettes manipulated by joysticks. With a narrow, bevel-tipped pipette, shebopped a sperm on the tail, immobilizing it so that she could draw it into thepipette’s chamber. Then she washed the sperm in the CRISPR solution. “Now it’sall going inside the oocyte,” she said. Invisibly, the CRISPR, with its guide-RNAprotein, found and cut MYH7. In minutes, she had made two edited human embryos.

I m'adono que hi ha una carrera de fons soterrada i fins i tot científicament hipòcrita que alhora que en públic moltes veus demanen responsabilitat, en privat aconsegueixen autoritzacions de recerca amb embrions. I això ja no passa a la Xina, sino també als Estats Units. De les implicacions ètiques i el que cal fer ja en vaig fer ressò aquí.

Moltes gràcies al New Yorker i a Dana Goodyear per aquest excel.lent reportatge, per guardar. Llegiu-lo sencer.

Dana Goodyear

PS. Aquest és exactament el tipus de periodisme que no sé trobar a Catalunya. 

PS. Per aquells que us va passar per alt, Francis Mojica des de les Salines de Santa Pola va ser el primer en tot això de CRISPR. Ho vaig explicar aquí. Ho dic perquè no va tenir cap suport, de la mateixa manera que van acomiadar a Núria Martí de l'Hospital de la Fe....

PS. CRISPR en context de l'evolució, ara, NOW:

The long and bumpy road to CRISPR (2)

 Editing Humanity. The CRISPR Revolution and the New Era of Genome Editing

In 2017 I wrote a post about the book by Jennifer Doudna, A Crack in Creation, now Kevin Davies, the editor of the CRISPR journal has published a new book on CRISPR. It is an effort to put all the information and details about CRISPR in one book. Therefore, if you want to now the whole story (or close to) this is the book to read. If you are interested in a general approach, then the Doudna book is better.

It is quite relevant the chapter that explains the role of Francis Mojica in CRISPR (chapter 3), and the chapter 18, on crossing the germline and what happened about the scandal of genome editing by JK.

“When science moves faster than moral understanding,” Harvard philosopher Michael Sandel wrote in 2004, “men and women struggle to articulate their own unease.” The genomic revolution has induced “a kind of moral vertigo.”49 That unease has been triggered numerous times before and after the genetic engineering revolution—the structure of the double helix, the solution of the genetic code, the recombinant DNA revolution, prenatal genetic diagnosis, embryonic stem cells, and the cloning of Dolly. “Test tube baby” was an epithet in many circles but five million IVF babies are an effective riposte to critics of assisted reproductive technology.

With CRISPR, history is repeating itself,

That's it, great book.