Bioethics. Группа авторов
Чтение книги онлайн.
Читать онлайн книгу Bioethics - Группа авторов страница 98
![Bioethics - Группа авторов Bioethics - Группа авторов](/cover_pre992447.jpg)
However, NIH will not fund any use of gene‐editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed. Advances in technology have given us an elegant new way of carrying out genome editing, but the strong arguments against engaging in this activity remain. These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos.
Practically, there are multiple existing legislative and regulatory prohibitions against this kind of work. The Dickey‐Wicker amendment prohibits the use of appropriated funds for the creation of human embryos for research purposes or for research in which human embryos are destroyed (H.R. 2880, Sec. 128). Furthermore, the NIH Guidelines state that the Recombinant DNA Advisory Committee, “…will not at present entertain proposals for germ line alteration”. It is also important to note the role of the U.S. Food and Drug Administration (FDA) in this arena, which applies not only to federally funded research, but to any research in the U.S. The Public Health Service Act and the Federal Food, Drug, and Cosmetic Act give the FDA the authority to regulate cell and gene therapy products as biological products and/or drugs, which would include oversight of human germline modification. During development, biological products may be used in humans only if an investigational new drug application is in effect (21 CFR Part 312).
NIH will continue to support a wide range of innovations in biomedical research, but will do so in a fashion that reflects well‐established scientific and ethical principles.
17 Genome Editing and Assisted Reproduction: Curing Embryos, Society or Prospective Parents?
Giulia Cavaliere
Introduction: Genetic Diseases, Genome Editing and Existing Alternatives
Different reproductive options are available for couples or individuals at risk of transmitting genetic diseases to their offspring who wish to have children. In this paper, I explore ethical and social questions raised by the use of genome editing into the context of assisted reproduction and, in particular, as a potential alternative to preimplantation genetic diagnosis (PGD).
Some of the reproductive options available to this group of individuals include refraining from having genetically related children and/or using technologies to reduce or avoid the risk of transmission. The first set of options includes adopting existing children or turning to third‐party reproduction (i.e. relying on a gamete donor). Adoption is currently legal in many European countries, but eligibility criteria vary. For instance, in some countries, access to this practice is limited to married heterosexual couples (e.g. Italy), while other countries have wider access criteria and allow same‐sex couples (e.g. the Netherlands and the United Kingdom) and single parents (e.g. France and the United Kingdom) to adopt. In addition, other criteria such as marital status and age play a role in the decision to grant adoption.
Another possibility to avoid transmission of genetic diseases is for individuals to have partly genetically‐related children and to seek gamete donors. This is commonly referred to as third‐party reproduction, which allows couples to have children who are genetically related to a donor and to the unaffected individual in the couple. Third‐party reproduction is currently only legal in some countries (e.g. the United Kingdom, the Netherlands and Spain) and usually restricted to heterosexual couples. Moreover, the state only subsidises IVF with donor gametes in a few countries (Gianaroli et al. 2016).
Alternatively, prospective parents at risk of transmitting genetic conditions to their offspring can seek to procreate with the aid of assisted reproductive technologies (ARTs) and preimplantation screening technologies (such as PGD), which would allow them to have genetically related children free from the condition that affects them (or one of them). PGD allows the testing of embryos created with IVF for genetic abnormalities prior to their transfer in utero. This technology is currently legal in many European countries (Gianaroli et al. 2016), but in some countries it remains restricted to so‐called ‘serious’ conditions (e.g. in Italy and Germany), and in others is completely banned (e.g. in Poland and Switzerland; Biondi 2013; Gianaroli et al. 2016). Across Europe, eligibility criteria vary. In the United Kingdom, for instance, the Human Fertilisation and Embryology Authority (HFEA) periodically revises and updates the lists of conditions that are eligible for screening with PGD. Other countries, such as Germany and Italy, recently approved the use of PGD, but access to this practice remains restricted to a very limited number of severe, early onset conditions (Biondi 2013; Gianaroli et al. 2016).
PGD and Assisted Reproduction
Where PGD is legal, it is typically used in cases where both prospective parents are carriers of an autosomal recessive mutation. These mutations are responsible for the occurrence of autosomal recessive monogenic diseases (i.e. diseases caused by a mutation in a single gene) such as cystic fibrosis and sickle cells anaemia.1 When both prospective parents are carriers of such mutations, future offspring have a 1 in 4 chance of inheriting the mutated gene and developing an autosomal recessive disease, while they have a 1 in 2 chance of inheriting one abnormal gene and thus becoming healthy carriers. PGD allows the testing and selection of embryos created through IVF to transfer in utero those that are either free from the abnormal gene related to the prospective parents’ condition (or that are carriers of such mutated gene when no mutation‐free embryo is obtained). PGD is also effective in cases where one of the prospective parents is heterozygous for an autosomal dominant mutation, meaning that they carry two different variants of a gene. Autosomal dominant mutations are responsible for the occurrence of diseases such as Huntington’s and neurofibromatosis type 1. Future offspring have a 1 in 2 chance of developing autosomal dominant diseases even if only one of the prospective parents is affected, because it is possible that the embryo would carry the ‘good’ genetic variant from both parents. If the embryo inherited the disease‐causing variant from only one parent, however, the resulting child would be affected by the disease.
It could be the case that none of the embryos created through IVF is free from the undesirable genetic mutation. For instance, when one of the prospective parents is homozygous for a dominant genetic disorder, the risk of transmission to offspring is as high as 100%, and hence no mutation‐free embryos can be obtained. In addition, when prospective parents are both heterozygous for a dominant genetic disorder, the risk of transmission is as high as 75%, hence the chances of finding mutation‐free embryos significantly low. Another case where PGD is not effective is when both parents are homozygous for a recessive genetic disorder, meaning that they both carry two variants of the disease‐causing gene (Nuffield Council on Bioethics 2016; Vassena et al. 2016). In such cases, genome editing could represent an alternative to PGD and a new reproductive option for some prospective parents: mutations potentially leading to monogenic diseases would be corrected in embryos created with IVF prior to the transfer in utero or directly onto prospective parents’ gametes prior to fertilisation. Lastly, gene editing could replace PGD for women at risk of transmitting mitochondrial diseases as mitochondrial DNA mutations present in oocytes2