Demand European Union to fund the research on embryonic stem cells and on genome editing in germ-line

Desideria Mini
Desideria Mini
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We, citizens of different countries, believe that the criteria for funding biomedical scientific research must consider all those researches that can protect and promote scientific progress in the treatment of serious diseases in order to guarantee the primary interest of patients and future generations of Mankind.

Therefore European institutions should not exclude a priori funding for the most promising frontiers of medicine and biology like studies about regenerative therapies (those are researches that try to develop methods to regrow, repair or replace damaged or diseased cells, tissues or organs, including generation and use of therapeutic stem cells, tissue engineering and the building of artificial organs) or about preventive medicine in the future of medically assisted procreation.

Scientific evidences show that research on embryonic stem cells and on human embryos with related genome editing are among the most promising techniques respectively+ to find cures for several types of severe diseases and to prevent inheritable ones in the offspring.

For these reasons we think the article 14 of the Horizon Europe proposal for funding research in the European Union from 2021 to 2027 must be changed.

The use of embryonic stem cells was effective both in preclinical trials for the treatment of neurodegenerative diseases in Lund, Cambridge and New York, where the clinical phase ought to start soon, and in clinical trials on blindness due to diseases in the retinal macula in London where several patients have recovered their sight. The respectively encouraging and excellent results of these researches have shown the effective therapeutic usefulness of the totipotent or pluripotent cells such as those of the embryo.

We believe that limiting the extraction of stem cells to supernumerary embryos (embryos left by medically assisted procreation cycles) might complicate the research of effective treatments and the application of the valid therapies that derive from it.

We also think the article 14 of the Horizon Europe proposal for funding research should not exclude activities intended to modify the genetic heritage of human beings, which could make such changes inheritable, when these are carried out for preventive purposes.

About 8000 monogenic diseases are known and each individual, often without knowing it, is a carrier of various mutations that can cause a genetic disease.

Today, fortunately, the new medical advances sometimes allow people affected by a hereditary genetic disease which reveals itself (or which anyway revealed itself) at young age to live (longer) and have a healthier life and this often allows them also to get to have children. Thank to research, in the future, this will be even more true, and for an increasingly number of hereditary genetic diseases. Obviously all that is a good news but this also means that harmful genetic variants are and will be always passed to children and therefore (also) to future generations.

So, due to medicine, natural selection is and will be missing in human species. This will have serious consequences, especially in the long term. Indeed the harmful genetic mutations inevitably accumulate in the absence of the natural selection, because harmful mutagenic events occur more frequently than beneficial ones. So, considering all that, about those (many) hereditary genetic diseases whose onset occurs (or may also occur) before or during the usual reproductive period of the individual's life, it is more than predictable that, moreover, their incidence in the human population over the generations will tend to increase, even up to a "point of unsustainability".

Similar principle apply to chromosomal diseases.

Unfortunately, pre-implantation genetic analysis of embryos (on its own) has limits that do not always make it sufficient or useful to deliver a "healthy" child and, in any case, a child not carrier of a dangerous genetic or chromosomal variant inherited from her\his parents and, in turn, transmissible to her\his future children. For people carrying a genetic disease who wish a child, the pre-implantation genetic analysis of embryos in order not to transmit the harmful genetic variant is usefull when both partners of a couple are heterozygous for a - recessive or not-recessive - genetic disease or when a person is heterozygous for a not-recessive genetic disease but it may be insufficient as the number of non-carrier embryos produced by in vitro fertilization may be low or zero, like it happens often, while, for the same purpose, it is useless when a person is homozygous for the genetic disease. The pre-implantation genetic analysis of embryos for the only outcome of giving birth to a "healthy" child is useful when at least one partner of a couple is heterozygous for a recessive genetic disease but it may be insufficient as even the total number of embryos "suitable for a pregnancy" may sometime be low or zero, while, for the same result, it is useless when both partners are homozygous for the recessive genetic disease and when a person is homozygous for a not-recessive genetic disease. To face the problem of the insufficiency of the "valid" embryos number, and only for that, the cycles of in vitro fertilization and pre-implantation genetic analysis can be repeated, nevertheless there is no certainty but only the probability of reaching the aforementioned objectives and so, in some cases, these can even never be reached.

The polar bodies biopsy is even more limiting because it allows the selection of genetic or chromosomal makeup coming only from female gametes, does not exclude possible cases of gene conversion, and is completely useless in case of aspiring mother's homozygosity.

(According to the research status, within a "few" years it could be possible to produce normal human sperm in vitro with safety, but selecting the secondary spermatocytes or the spermatids will be very hard due to their cytological features, besides presenting limits analogous to those of polar bodies biopsy.)

However, if appropriate basic research were carried out on human “fertilized oocytes”, zygotes and precursor stem cells of the gametes (on spermatogonia or on reprogrammed induced pluripotent stem cells) one day predictably it may become possible to modify the human genome in hereditary way with safety and efficacy. Only then we could decide whether to apply the results of such research in the clinic to reduce the incidence of hereditary diseases, or at least to stop their spread, still remembering, however, that these researches are first carried out in vitro also on human cells, otherwise this will never be possible.

Indeed we believe that in the future safe and effective inheritable treatments for hereditary diseases should be allowed (and perhaps also encouraged, at least for more serious them) because they would prevent the disease for all the descendants. That would avoid having to cure and heal people for each generation, something of which, moreover, there would be need more and more.

We do not claim that this line of research is superior to others or that research into somatic genetic therapies should not be funded. We just want to say that in vitro research on "germ-line genetic therapies" (in quotation marks because it would be more accurate to speak of "in germ-line genetic prevention by genetic modification") are complementary and very important so that such research should not be excluded a priori from funding.

For all the reasons expressed we also believe that funding should also be allowed whenever it is directed to activities intended to create human embryos and to let them develop within the first fourteen days (excluding the period of eventual cryo-preservation) also solely for the purpose of research, like germ-line genome editing in vitro experiments and genetically edited embryos initial development studies, or for the purpose of stem cell procurement.

In particular, for germ line genome editing experiments, the use of sole supernumerary embryos would be problematic and limiting. The embryo is multicellular and cryo-preserved embryos can be early embryos, morulae or blastocysts. In the case of the early embryo it is still possible to utilize the embryo splitting to obtain single totipotent cells to genetically edit, and from each of them to derive a new embryo but these embryos do not develop as well as not-splitted embryos do. However the vaste majority of supernumerary embryos is at morula or blastocyst stages and starting from the morula stage cells are too little to deliver a new embryo from each of them, so morula and blastocyst do not permit similar strategy. Besides the blastocyst is also more complex than the morula and its cells are not more totipotent and are even more little. Therefore in the case of morulae and blastocyst to be sure of always and only acting in a beneficial way and also in the germinal line, it would be necessary to genetically modify every cell of the embryo - inner cell mass for the blastocyst - and in a precise, effective and correct way for each cell, and without accidentally damages for every one of them. Furthermore, the use of (sole) supernumerary embryos would not allow the study of the development of embryos deriving from genetically edited "fertilized oocytes" and zygotes, or coming from fertilization with genetically edited gametes (to get throught the genome editing of their precursor stem cells).

We also believe that funding should also be allowed including the somatic cell nuclear transfer for the purpose of stem cell procurement because the transfer of the nucleus of a somatic cell of a patient into an egg cell deprived of its nuclear genetic material would allow the production of embryonic stem cells compatible with the patient's own immune system, in order to avoid the transplant rejection.

It is also important that in the future the results of all these researches are shared among the people and benefit the entire world population.

For this reason we also believe that it is wrong to let these researches take place only outside the European Union.

We urge Members of the European Parliament, EU Commissioners and Governmental representatives to revise the criteria for "Eligible actions and ethical principles" for funding biomedical researches of the Horizon Europe 2021 – 2027 in line with the present petition.

So we ask to emend the letters (b) and (c) of Article 14 of the Horizon Europe 2021 – 2027 as follow:

(b) activities intended to modify the genetic heritage of human beings which could make such changes heritable, except for preventive purposes;

(c) activities intended to create human embryos solely for the purpose of research or for the purpose of stem cell procurement, including by means of somatic cell nuclear transfer, if it's planned that embryos develop for more than fourteen days or if there are other valid alternatives.

We, the undersigned