Peut-on hacker son ADN de chez soi ?

Alors que les thérapies géniques autorisées coûtent une fortune, quelques biohackers veulent les rendre accessibles au plus grand nombre.

Sélec­­tion contre-nature

Devant une fenêtre aux rideaux noués l’un à l’autre, Josiah Zayner distille un liquide jaunâtre dans une éprou­­vette. Une lampe de bureau pallie le ciel rembruni d’Oak­­land, en Cali­­for­­nie. Sa lumière arti­­fi­­cielle fait scin­­tiller les pier­­cings de l’homme de 38 ans, dont le visage barbu, coiffé par une tein­­ture blonde, paraît bien plus jeune. Ce program­­meur, titu­­laire d’une thèse de biolo­­gie, n’a pas encore de cure de jouvence, mais il est persuadé d’être sur la bonne voie avec le maté­­riel d’édi­­tion de l’ADN qu’il élabore chez lui.

Puisque « les choses ne changent pas à moins que le corps médi­­cal n’ait d’autre choix que de chan­­ger », Zayner mène ses expé­­ri­­men­­ta­­tions aux fron­­tières de la léga­­lité. Après avoir sorti deux grenouilles de boîtes, il compare leurs poids sur de petites balances. Celle qui a reçu une théra­­pie génique pèse 1,6 gramme de plus que l’autre. « L’IGF-1 vous fait prendre de la masse », observe-t-il en réfé­­rence à une hormone pepti­­dique. Sa société, The Odin, vend ainsi un kit pour apprendre à modi­­fier géné­­tique­­ment les animaux.

Josiah Zayner
Crédits : San Jose Mercury News

En octobre 2017, le chef d’en­­tre­­prise s’était injecté « de l’ADN avec une poly­é­thy­­lé­­nei­­mine » dans le but de « modi­­fier les gènes de [s]es muscles pour les faire gros­­sir ». Alors que sa physio­­no­­mie n’a semble-t-il pas bougé depuis, sa boîte e-mail a gonflé. « Je rece­­vais aupa­­ra­­vant un message par jour, j’en ai main­­te­­nant une dizaine », constate-t-il dans le deuxième épisode de la série docu­­men­­taire Sélec­­tion contre-nature, actuel­­le­­ment diffu­­sée par Netflix.

On y fait aussi la rencontre de Tris­­tan Robert, un homme séro­­po­­si­­tif qui expé­­ri­­mente une théra­­pie génique sans l’aval des méde­­cins, et de Jack­­son Kennedy, un petit garçon atteint d’une mala­­die géné­­tique qui risque de le rendre aveugle si le trai­­te­­ment – approuvé par la Food and Drug Admi­­nis­­tra­­tion (FDA) – ne fonc­­tionne pas. En géné­­ral, Zayner est contacté par « des gens qui sont grave­­ment malades. Ils sont atteints de dystro­­phies muscu­­laires, [et me contactent] parce que j’ai fait cette expé­­rience avec CrispR sur mes muscles. »

Déve­­loppé il y a sept ans, CrispR est un outil parti­­cu­­liè­­re­­ment promet­­teur. Jusqu’à présent, la théra­­pie génique consis­­tait à déli­­vrer un gène sain à une cellule afin de suppléer un gène défaillant à l’ori­­gine d’une mala­­die. Il pouvait être injecté direc­­te­­ment dans l’or­­ga­­nisme (in vivo) au moyen d’un médi­­ca­­ment en cas d’in­­suf­­fi­­sances muscu­­laires, respi­­ra­­toires, oculaires, cardiaques ou neuro­­lo­­giques. Pour les mala­­dies sanguines, un prélè­­ve­­ment de cellules était néces­­saire (ex vivo). Ces deux tech­­niques ont abouti à la créa­­tion de médi­­ca­­ments comme le Strim­­ve­­lis, le Glybera ou le Luxturna. Selon un rapport publié l’an dernier par Trans­­pa­­rency Market Research (TMR), le marché des théra­­pies géniques doit croître de 40 % entre 2018 et 2026.

Grâce à la protéine Cas9, CrispR va plus loin en offrant la possi­­bi­­lité de couper l’ADN à un endroit précis pour lui permettre de retrou­­ver un gène fonc­­tion­­nel. Le 21 octobre dernier, des cher­­cheurs du Massa­­chu­­setts Insti­­tute of Tech­­no­­logy et de Harvard ont même trouvé une autre protéine, la trans­­crip­­tase inverse, qui pour­­rait permettre de corri­­ger 89 % des défauts géné­­tiques. Quatre jour plus tôt, une équipe espa­­gnole expliquait avoir allongé la durée de vie de souris grâce à une troi­­sième protéine, la télo­­mé­­rase, sans avoir à modi­­fier leur génome.

Un kit vendu par The Odin

Mais alors que de nombreux tests devront encore être réali­­sés pour confir­­mer ces résul­­tats, des bioha­­ckers comme Tris­­tan Robert ou Josiah Zayner font fi des cadres métho­­do­­lo­­giques qui gouvernent la science en expé­­ri­­men­­tant les théra­­pies géniques sur eux-mêmes. « Je n’ai pas de préoc­­cu­­pa­­tions morales ou éthiques au sujet de l’édi­­tion géné­­tique », tranche le second. « Je suis plus inquiet par la pers­­pec­­tive d’une régu­­la­­tion du gouver­­ne­­ment qui empê­­che­­rait aux gens d’y avoir accès. » Le patron de The Odin dit vouloir offrir au grand public des trai­­te­­ments encore très chers quand ils ne sont pas tout bonne­­ment inter­­­dits.

Le 8 mai dernier, Josiah Zayner a reçu une convo­­ca­­tion du Dépar­­te­­ment des consom­­ma­­teurs de Cali­­for­­nie, qui venait de lancer une enquête à son encontre. Son acti­­vité a aussi suffi­­sam­­ment inquiété la séna­­trice Répu­­bli­­caine de Cali­­for­­nie Ling Ling Chang pour qu’elle la cite dans son projet de loi visant à régle­­men­­ter l’uti­­li­­sa­­tion de l’ou­­til CrispR. Signée par le gouver­­neur le 30 juillet, le texte devrait entrer en vigueur en janvier 2020. « CrispR devient acces­­sible à un large public, mais beau­­coup, au sein de la commu­­nauté scien­­ti­­fique, s’alarment qu’il pour­­rait avoir des effets néfastes en dehors de labo­­ra­­toires profes­­sion­­nels », justi­­fie Chang.

Si la vente d’ou­­tils d’édi­­tion géné­­tique pour l’hu­­main est illé­­gale aux États-Unis d’après la FDA, The Odin a arrêté d’en vendre car, à force de vouloir aller plus loin, « les gens vont se faire du mal », avoue Zayner. Désor­­mais, la société ne propose plus que des kits pour modi­­fier le génome d’ani­­maux, libre à ceux qui veulent expé­­ri­­men­­ter sur eux-mêmes de détour­­ner leurs usage… Le 25 septembre 2019, le Dépar­­te­­ment des consom­­ma­­teurs de Cali­­for­­nie a donc mis fin à son enquête sans prévoir de mesure contre le bioha­­cker.

Le grand biohack

Un petit homme chauve s’avance vers la scène de l’hô­­tel Renais­­sance, à Las Vegas. Plutôt que de prendre place sur un des trois fauteuils rouges, il s’as­­soit sur le rebord et pose son ordi­­na­­teur portable près de lui. « Gabriel Licina est un biolo­­giste molé­­cu­­laire et un adepte de la biolo­­gie open-source », explique la présen­­ta­­trice de la confé­­rence Biohack the Planet en ce mois de septembre 2019. « Il a ouvert des labo­­ra­­toires et déve­­loppé des projets de biolo­­gie en dehors du cadre acadé­­mique pendant 10 ans. Il s’in­­té­­resse à la santé, à la longé­­vité et biore­­me­­dia­­tion. » Son visage a fait le tour du monde quand Licina a noirci ses yeux en y injec­­tant une solu­­tion à base de chlo­­rine e6 aux proprié­­tés photo-sensi­­bi­­li­­sa­­trices.

Le fonda­­teur de Scihouse Inc. est venu parler du Glybera, une théra­­pie génique conçue pour soigner le défi­­cit fami­­lial en lipo­­pro­­téine lipase. Cette mala­­die rare « entraîne de grandes souf­­frances », prévient Licina. Approuvé aux États-Unis en 2015, le Glybera « a été mis sur le marché pour un million de dollars », pour­­suit-il avec un sourire plein de sarcasmes. Il n’a donc été vendu qu’une fois, à une Alle­­mande dont le méde­­cin s’est battu pour que son assu­­rance couvre le trai­­te­­ment. Puis il a été retiré. Il existe donc une entre­­prise, uniQure, qui détient le brevet sans rien en faire. « C’est fou, ils sont confor­­ta­­ble­­ment assis à regar­­der des gens souf­­frir à cause de l’argent », s’agace-t-il.

Gabriel Licina

Alors Licina a décidé de régler le problème. Deux mois plus tôt, un scien­­ti­­fique autri­­chien lui avait suggéré de compo­­ser une copie du Glybera en repre­­nant la séquence géné­­tique décrite dans la litté­­ra­­ture scien­­ti­­fique. Moyen­­nant 7 000 dollars, il est appa­­rem­­ment parvenu à la faire fonc­­tion­­ner sur des cellules de mammi­­fère. Cette version pirate est entre ses mains à l’hô­­tel Renais­­sance de Las Vegas. Le bioha­­cker la donne à tous ceux qui veulent la déve­­lop­­per dans un labo­­ra­­toire de biolo­­gie. « Mais ne commen­­cez pas par vous l’injec­­ter », prévient-il. « S’il vous plaît, pour l’amour de Dieu, arrê­­tez de vous muti­­ler. »

Pour John Kaste­­lein, un scien­­ti­­fique néer­­lan­­dais qui a parti­­cipé à l’éla­­bo­­ra­­tion de la Glybera, cette théra­­pie génique est trop complexe pour pouvoir être bioha­­ckée. Ce serait même « sans espoir ». Même s’il consi­­dère le projet de Licina comme une tenta­­tive bien­­ve­­nue d’ou­­vrir l’ac­­cès aux nouveaux trai­­te­­ments, le docteur Daniel Gaudet voit aussi mal comment il pour­­rait abou­­tir. Les moyens qui permettent de garan­­tir sécu­­rité et effi­­ca­­cité aux patients sont pour lui hors de portée des bioha­­ckers. «  Le Glybera était trop cher, c’est fini », tranche ce spécia­­liste cana­­dien qui a conduit les premiers essais cliniques.

Comme le montre le rapport de Trans­­pa­­rency Market Research (TMR) suscité, ce domaine de recherche ne manque pour­­tant pas d’argent. Mercredi 23 octobre, les Insti­­tuts améri­­cains de la santé (NIH), qui dépendent du Dépar­­te­­ment fédé­­ral de la santé, ont annoncé qu’il allaient inves­­tir 100 millions de dollars ces quatre prochaines années pour déve­­lop­­per des théra­­pies géniques contre les mala­­dies géné­­tiques et le sida. La Fonda­­tion Bill & Melinda Gates a promis le même inves­­tis­­se­­ment. En mars, un patient séro­­po­­si­­tif traité avec des cellules souches est entré en phase de rémis­­sion.

Crédits : The Odin

Ces dix dernières années, les trai­­te­­ments géné­­tiques ont fait « des progrès fulgu­­rants, y compris pour trai­­ter la cécité et certains types de leucé­­mie ». Seule­­ment, leurs coûts élevés les rendent « inac­­ces­­sibles » en dehors de pays riches. Les NIH et la Fonda­­tion Bill & Melinda Gates disent donc vouloir favo­­ri­­ser leur acces­­si­­bi­­lité. À l’hô­­pi­­tal pour enfants St. Jude de Memphis, les méde­­cins ont déjà appliqué une théra­­pie génique expé­­ri­­men­­tale à un enfant atteint de défi­­cit immu­­ni­­taire combiné sévère. Ils lui ont extrait de la moelle osseuse pour corri­­ger le gène défaillant avant de lui réin­­tro­­duire.

« D’un point de vue physio­­lo­­gique et de qualité de vie, cela fonc­­tionne », avance le méde­­cin de St. Jude, James Downing. « Reste à savoir si ce sera durable. Est-ce que cela durera 10, 20 ou 50 ans pour ces enfants ? Nous ne le saurons qu’a­­vec le temps. » Pour certains malades, ce temps est évidem­­ment précieux. Mais ce genre de théra­­pies est suscep­­tible de provoquer des leucé­­mies ou des effets secon­­daires impor­­tants. Autre­­ment dit, aucun méde­­cin sérieux ne conseillera à ses patients de toucher à son ADN à la maison. Josiah Zayner regrette d’ailleurs d’avoir publique­­ment utilisé CrispR sur lui-même. « Je m’en veux car les gens le voient main­­te­­nant comme un moyen de deve­­nir connu », souffle-t-il. « Et certains vont se faire du mal, ça ne fait aucun doute. » Il n’y a en revanche pas de souci à se faire pour sa société, The Odin.


Couver­­ture : DR

Source : Ulyces

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