09.-Utilisation des biotechnologies sur les cellules embryonnaires et germinales humaines / Use of biotechnologies on human embryonic and germ cells — CHURCH OF FRANCE / États généraux de la bioéthique — States General on Bioethics

http://eglise.catholique.fr/sengager-dans-la-societe/eglise-et-bioethique/comprendre-les-enjeux/

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Current scientific and legal data

The OECD defines biotech­nol­o­gy as “the appli­ca­tion of sci­ence and tech­nol­o­gy to liv­ing organ­isms, as well as its com­po­nents, prod­ucts and mod­el­ling, to mod­i­fy liv­ing or non-liv­ing mate­ri­als for the pro­duc­tion of knowl­edge, goods and services”.

Biotech­nolo­gies are used today for the pro­duc­tion of drugs by liv­ing organ­isms with mod­i­fied genomes, giv­ing “bio-drugs” (ex: artemisinin to fight against malar­ia). They make pos­si­ble an engi­neer­ing of the liv­ing and espe­cial­ly a “genom­ic engi­neer­ing” thanks to a set of tech­niques which allow:

• To cor­rect the DNA sequence (bio­log­i­cal mol­e­cule present in the nucle­us of our cells and the sup­port of our genet­ic identity),
• Delete one or more genes,
• To insert in a genome one or more genes which can either come from anoth­er organ­ism, or be syn­the­sized in laboratory.

The GMO (genet­i­cal­ly mod­i­fied organ­ism) is the result of these genom­ic manip­u­la­tions. For exam­ple, “trans­ge­n­e­sis” is a tech­nique that allows a DNA sequence to be insert­ed into liv­ing beings. Syn­thet­ic biol­o­gy” enables the ratio­nal design of new “arti­fi­cial” bio­log­i­cal sys­tems, some of which are used for med­ical diag­no­sis of HIV patients. Both tech­niques enrich “gene ther­a­py” which is the use of genet­ic manip­u­la­tion of human cells to treat a disease.

Advances in gene ther­a­py make it pos­si­ble to fight genet­ic dis­eases thanks to the strong poten­tial of human stem cells (embry­on­ic, IPS and adults…). More­over, thanks to high-through­put genome sequenc­ing tech­niques, par­tic­u­lar­ly applied to the intesti­nal “micro­bio­ta” of humans (their intesti­nal flo­ra), we believe we will be able in the near future to con­tribute to the treat­ment of com­plex patholo­gies such as can­cers and car­dio­vas­cu­lar dis­eases influ­enced by the genom­ic state of the “micro­bio­ta”.

A new tech­nol­o­gy, more pow­er­ful than pre­vi­ous ones in terms of accu­ra­cy, speed, reli­a­bil­i­ty and low cost, is rev­o­lu­tion­iz­ing gene ther­a­py: CRISPR/Cas9, or “DNA scis­sors”. This tech­nique allows DNA sequences to be removed, added or mod­i­fied in an extreme­ly well tar­get­ed man­ner. It is no longer just a ques­tion of man­u­fac­tur­ing a drug, but of act­ing direct­ly on human cells. For exam­ple, we may con­sid­er replac­ing a gene car­ry­ing a genet­ic dis­ease with a healthy gene, or mod­i­fy­ing gene expres­sion and cor­rect­ing altered func­tions. The appli­ca­tion pos­si­bil­i­ties of CRISPR/Cas9 are mul­ti­ple, in biol­o­gy and med­i­cine. This tech­nique applies to any species, to all the bio­di­ver­si­ty of liv­ing organ­isms, human in par­tic­u­lar. (The first clin­i­cal tri­als took place in 2016 in the USA on immune cells to fight against cer­tain can­cers. Oth­er tri­als have been con­duct­ed in Chi­na on non-viable human embryos).

Questions this raises:

The main chal­lenge of CRISPR/Cas9 is that not enough is known about the role of all genes and, there­fore, the long-term con­se­quences of such changes on the genome, par­tic­u­lar­ly in humans. In addi­tion, unwant­ed side effects, called “off-tar­get” effects, may occur.

When a human somat­ic cell is mod­i­fied (from the human body as opposed to the germ cells that donate gametes), the mod­i­fi­ca­tions only con­cern the per­son in ques­tion. There must there­fore be sci­en­tif­ic val­i­da­tion of the pro­posed amend­ment, an eval­u­a­tion of the benefit/risk ratio (can we go back in case of neg­a­tive eval­u­a­tion in time?), an ethics of respect for the integri­ty of the per­son, and, of course, the informed con­sent of the per­son concerned.

For human germ cells and for zygote, their mod­i­fi­ca­tions would be trans­mit­ted to the off­spring. The sit­u­a­tion is there­fore com­plex: on the one hand there is irre­versibil­i­ty of trans­mis­sion and, on the oth­er, future changes by epi­ge­net­ic fac­tors (which take into account the effects of inter­ac­tions between genes and oth­er envi­ron­men­tal fac­tors such as liv­ing con­di­tions). More­over, seri­ous con­se­quences can occur if, at the same time as the genet­ic cor­rec­tion sought, an error is trans­mit­ted, which is always pos­si­ble with gene edit­ing meth­ods. How can the pre­cau­tion­ary prin­ci­ple and the prin­ci­ple of respon­si­bil­i­ty be tak­en into account, par­tic­u­lar­ly with regard to future generations?

The Inter­na­tion­al Bioethics Com­mit­tee of UNESCO recalls that the use of CRISPR/Cas9 rais­es seri­ous con­cerns with regard to human genome engi­neer­ing. The Com­mit­tee called for a mora­to­ri­um “on tech­niques for edit­ing the DNA of human repro­duc­tive cells in order to avoid uneth­i­cal changes in the hered­i­tary char­ac­ter­is­tics of indi­vid­u­als, which could bring about a resur­gence of eugen­ics”. Indeed, if the tech­nique is promis­ing, because it “opens per­spec­tives to treat or even cure cer­tain dis­eases in a sim­ple and effec­tive way” such as cys­tic fibro­sis and cer­tain can­cers, it can also give for exam­ple the pos­si­bil­i­ty of mod­i­fy­ing human DNA to “deter­mine the colour of the baby’s eyes[1]”.

Under the aegis of the Coun­cil of Europe, the Oviedo Con­ven­tion of 4 April 1997, rat­i­fied to date by 29 coun­tries includ­ing France (but not the Unit­ed King­dom, nor the Unit­ed States and Chi­na), stip­u­lates in its Arti­cle 13 that “an inter­ven­tion intend­ed to mod­i­fy the human genome may be under­tak­en only for pre­ven­tive, diag­nos­tic or ther­a­peu­tic rea­sons and only if its aim is not to intro­duce a mod­i­fi­ca­tion in the genome of the descen­dants”. To date, it is the only inter­na­tion­al legal instru­ment for the pro­tec­tion of human rights in the bio­med­ical field.

Anthropological and ethical aims:

Using CRISPR/Cas9 to attempt an ulti­mate pos­si­bil­i­ty of cur­ing a seri­ous dis­ease by act­ing on somat­ic cells, can be ben­e­fi­cial if eth­i­cal and safe­ty con­di­tions are ensured. Using it on zygotes and germ cells or to “increase the human” accord­ing to one’s own desires is par­tic­u­lar­ly dan­ger­ous: how far can man be the design­er of his own evo­lu­tion, already today and for future gen­er­a­tions? Life is received and giv­en, we do not own it. The human genome does not belong to sci­ence and sci­en­tists, nor to any nation or inter­na­tion­al orga­ni­za­tion. Can man thus appro­pri­ate the human genome as a “thing that can be manip­u­lat­ed at will”? Can he appro­pri­ate the human liv­ing as a com­mod­i­ty, patent it by bring­ing it into the com­mer­cial sys­tem, rede­fine it accord­ing to his views?

The Inserm Ethics Com­mit­tee, in a rec­om­men­da­tion on genome edit­ing technologies[2], draws atten­tion “to the more philo­soph­i­cal ques­tion that puts the plas­tic­i­ty of the liv­ing under ten­sion with the idea of a human nature based sole­ly on the bio­log­i­cal invari­ant. It is nec­es­sary to cre­ate an aware­ness that takes into account the utopia and dystopias that cer­tain ther­a­peu­tic promis­es can gen­er­ate. This opin­ion is not unre­lat­ed to the anthro­po­log­i­cal pos­ture of the “vul­ner­a­ble human being, cor­ner­stone of ethics[3]”, dear to Chris­t­ian tra­di­tion, as shown in the card on the biol­o­gy-psy­chism links in all liv­ing beings.

Anoth­er aspect requires our vig­i­lance: how to look at the dis­abled per­son at the time of CRISPR/Cas9 and new gene ther­a­pies? Is life only worth liv­ing when we can repair or even increase our func­tion­al­i­ty? Giv­en the cur­rent influ­ence of cer­tain so-called tran­shu­man­ist cur­rents, the inalien­able dig­ni­ty of every human being deserves to be recalled.

Bib­li­o­graph­i­cal ref­er­ences to con­tin­ue the work

• Edgar­do Carossela (sous la dir.), Nature et Arti­fice. L’homme face à l’évolution de sa pro­pre essence, Her­mann, 2014.
• Jür­gen Haber­mas, L’Avenir de la nature humaine-Vers un eugénisme libéral ?, Gal­li­mard, 2015.
• Thier­ry Magnin, Les nou­velles biotech­nolo­gies en ques­tions, Sal­va­tor, 2013 ; Penser l’humain au temps de l’homme aug­men­té, Albin Michel, 2017.

2 févri­er 2018

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[1] Avis d’octobre 2015.

[2] Site web de l’Inserm, 13 juin 2016.

[3] Voir Mgr Pierre d’Ornellas, Au coeur du débat bioéthique, Dig­nité et vul­néra­bil­ité, Doc­u­ments Épis­co­pat, n. 6, 2010, p. 11.