01.-Therapie germinale / Germinal Therapy — 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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Scientific and legal elements :

There are two types of gene ther­a­py: somat­ic and germline.
Somat­ic gene ther­a­py con­sists in act­ing on cer­tain non-repro­duc­tive cells to elim­i­nate or reduce genet­ic defects. The effects are lim­it­ed to the indi­vid­ual treat­ed. Clin­i­cal tri­als are under­way with some suc­cess in rela­tion to sick­le cell dis­ease (genet­ic dis­ease of the blood) or cer­tain forms of leukaemia.

Germ-line gene ther­a­py involves mod­i­fy­ing a gene so that it is then trans­mit­ted to the sub­jec­t’s off­spring. This can be done in two ways:

• either on a very young embryo at the zygote stage[1],
• either on germ cells (gamete pro­duc­ers) or gametes (sperm and eggs) dur­ing their formation.

The embryo or gametes on which the research is being con­duct­ed are cur­rent­ly manip­u­lat­ed in vit­ro. Male gametes are removed by mas­tur­ba­tion and female gametes are removed by punc­ture after hor­mon­al stim­u­la­tion. Inter­ven­tion on gamete or embryo DNA is per­formed by insert­ing, cor­rect­ing or remov­ing a small, well-defined seg­ment of DNA (CRISPR-Case technique9). This results in a change in the genome of the embryo or future embryo, which is poten­tial­ly trans­mis­si­ble. In the long term, the genet­ic her­itage of the human species could be grad­u­al­ly modified.

Remem­ber that the gamete for­ma­tion process (“mei­ot­ic recom­bi­na­tion”) results, on the one hand, in an indi­vid­u­al’s germ cells not hav­ing the same genet­ic sequence as that of his somat­ic cells, and, on the oth­er hand, in each gamete hav­ing a unique genet­ic code.

If we also take into account the fact that the vast major­i­ty of dis­eases “depend on many genes as well as envi­ron­men­tal fac­tors and lifestyles,[2]” we under­stand that genet­ic engi­neer­ing can­not be an easy solu­tion for treat­ing most dis­eases. How­ev­er, CRISPR-Cas9 appli­ca­tion research in mice has shown promis­ing results in the treat­ment of Duchenne mus­cu­lar dystrophy.

Legal­ly, Arti­cle 13 of the Oviedo Con­ven­tion, rat­i­fied by France, stip­u­lates that “an inter­ven­tion intend­ed to mod­i­fy the human genome may be under­tak­en only for pre­ven­tive, diag­nos­tic or ther­a­peu­tic rea­sons, and only if it is not intend­ed to intro­duce a mod­i­fi­ca­tion in the genome of the descen­dants”. Ger­mi­nal gene ther­a­py is there­fore pro­hib­it­ed in France today.

How­ev­er, the Acad­e­my of Med­i­cine has pro­posed autho­riz­ing research on germ cells and embryos “when sci­en­tif­i­cal­ly and med­ical­ly justified.

Anthropological and Ethical Issues

As Pope Fran­cis recalled, if tech­nique, well direct­ed, can “pro­duce tru­ly pre­cious things for the qual­i­ty of life of the human being”, it can also give us “a ter­ri­ble pow­er”, even “an impres­sive hold over the whole of humanity[4]”. Germ-line gene ther­a­py expos­es to such a risk. Here are four points of discernment.
1. Gen­er­al prin­ci­ple of pre­cau­tion: “We still know too lit­tle about genet­ic inter­ac­tions and the pos­si­ble unin­tend­ed con­se­quences of the mod­i­fi­ca­tion of the human genome. By elim­i­nat­ing some harm­ful pre­dis­po­si­tions, oth­er prob­lems could appear and expose indi­vid­u­als and the human species itself to oth­er risks poten­tial­ly as seri­ous as those we could solve.

2. Respect for the most vul­ner­a­ble: pru­dence calls for inter­na­tion­al reg­u­la­tion of research and its appli­ca­tions to guar­an­tee, in par­tic­u­lar, “respect for vul­ner­a­ble per­sons and per­son­al integri­ty”, “non-dis­crim­i­na­tion and non-stigma­ti­za­tion” and “pro­tec­tion of future generations[6]”. On the lat­ter cri­te­ri­on, it should be not­ed that the mod­i­fi­ca­tion of the genet­ic her­itage of gametes or human embryos in the very ear­ly stages of their growth would have con­se­quences for the whole lives of future chil­dren. By touch­ing the genet­ic struc­ture of their body, it is their free devel­op­ment that is conditioned[7].

3. Banal­iza­tion of gametes and embryo com­mod­i­fi­ca­tion: gametes are col­lect­ed and manip­u­lat­ed out­side any con­ju­gal rela­tion­ship. As far as embryos are con­cerned, both research and the appli­ca­tion of gene ther­a­py are car­ried out with­in the tech­ni­cal frame­work of in vit­ro fer­til­i­sa­tion. This means that human embryos will be han­dled, frozen, sort­ed and some destroyed. The human embryo is there­fore chosi­fied until destruction.

4. Eugen­ics: “Such manip­u­la­tions pro­mote an eugenic men­tal­i­ty and intro­duce an indi­rect social stigma­ti­za­tion towards those who do not pos­sess cer­tain par­tic­u­lar qual­i­ties. These manip­u­la­tions raise the for­mi­da­ble ques­tion of “who would deter­mine which of these mod­i­fi­ca­tions would be pos­i­tive and which would not[8]”.

While somat­ic gene ther­a­py can be wel­comed as a promis­ing advance, sub­ject to the pre­cau­tions com­mon to all research and ther­a­peu­tic pro­to­cols, germline gene ther­a­py rais­es seri­ous eth­i­cal ques­tions, already expressed by some mem­bers of the inter­na­tion­al sci­en­tif­ic community.

The pro­posed dif­fer­ence between free­dom of research and con­trol of appli­ca­tions ignores the anthro­po­log­i­cal issues under­ly­ing sci­en­tif­ic research and tends to sub­or­di­nate ethics sole­ly to the cri­te­ri­on of effec­tive­ness. For the rea­sons stat­ed above, we can say that germline gene ther­a­py today does not offer the qual­i­ties nec­es­sary for ther­a­peu­tic action respect­ful of human dig­ni­ty and equal­i­ty between men.

Feb­ru­ary 1, 2018

[1] Cel­lule résul­tant de la fusion d’un sper­ma­to­zoïde et d’un ovule. Pre­mier stade de la vie d’un individu.
[2] Comité Inter­na­tion­al de Bioéthique de l’UNESCO, Rap­port du CIB sur la mise à jour de sa réflex­ion sur le génome humain et les droits de l’homme, 2015, n°103.
[3] Académie Nationale de Médecine, Rap­port « Mod­i­fi­ca­tions du génome des cel­lules ger­mi­nales et de l’embryon humain », 12 avril 2016.
[4] FRANÇOIS, Let­tre ency­clique Lauda­to Si’, 2015, n°103–104.
[5] UNESCO, Rap­port du CIB…, n°105.
[6] UNESCO, Rap­port du CIB…, n°116.
[7] Cf. J. HABERMAS, L’avenir de la nature humaine. Vers un eugénisme libéral ?, Gal­li­mard, 2002,
[8] CONGRÉGATION POUR LA DOCTRINE DE LA FOI, Instruc­tion « Dig­ni­tas Per­son­ae » sur cer­taines ques­tions de bioéthique, 2008, n°27.