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Ethics of preimplantation genetic diagnosis
RBMOnline O - Vol 14. Suppl. 1. 2007 102–103 Reproductive BioMedicine Online; www.rbmonline.com/Article//2646 on web 1 November 2006
%THICS OF PREIMPLANTATION GENETIC DIAGNOSIS $R 9URY 6ERLINSKY IS A GRADUATE POST GRADUATE AND 0H$ OF +HARKOV 5NIVERSITY IN THE FORMER 5332 (IS RESEARCH INTERESTS INCLUDE CYTOGENETICS EMBRYOLOGY AND PRENATAL AND PREIMPLANTATION GENETICS (E INTRODUCED POLAR BODY TESTING FOR PREIMPLANTATION GENETIC DIAGNOSIS AND DEVELOPED THE METHODS FOR KARYOTYPING SECOND POLAR BODY AND INDIVIDUAL BLASTOMERES (E HAS PUBLISHED OVER PAPERS AS WELL AS THREE BOOKS ON PREIMPLANTATION GENETICS
$R 9URY 6ERLINSKY 9URY 6ERLINSKY 2EPRODUCTIVE 'ENETICS )NSTITUTE .ORTH (ALSTED 3TREET #HICAGO ), 53! #ORRESPONDENCE E MAIL RGI FLASHNET
!BSTRACT This paper briefly reviews the current status of preimplantation genetic diagnosis (PGD), to offer a basis for discussion about its ethical background. It describes the situation regarding modern types of PGD, which involve analyses on the inheritance by human embryos of chromosomal disorders or gene mutations. The current scale of these treatments is discussed, together with the progress of new advances such as ‘designer babies’. Brief reference is made to the first meeting in this series. Keywords: designer babies, ethics, preimplantation genetic diagnosis
)NTRODUCTION It is a pleasure to speak to this conference. My topic today concerns the application of preimplantation genetic diagnosis (PGD) to the study of deleterious gene mutations in an embryo or the analysis of its chromosomal complement in order to select those embryos which are diploid for transfer to their mother. Embryos carrying these defects are identified by excising a single blastomere which enables their chromosomal complement by means of fluorescent in-situ hybridization (FISH). If needed, a second biopsy can be performed at the blastocyst stage to corroborate the first diagnosis or to check the possibility of mosaicism in the embryo. A few thousands of babies have already been born, with approximately 1000 involving gene diagnosis and the rest chromosomal diagnosis. Diagnoses can also be achieved in many cases by excising and diagnosing the first and second polar bodies to gain information on the oocyte genotype. The results of this work were discussed in my earlier contribution to the London meeting on Moral Philosophy and Assisted Reproduction (Verlinsky, 2005), and some specific aspects of these treatments will be outlined in this paper.
It has become very evident over the last decade that an extraordinarily high proportion of human embryos are chromosomally abnormal. These effects range from monosomy and trisomy to various forms of polyploidy, translocations, deletions and other genetic defects. This approach to assessing embryos by chromosomal analyses is becoming a regular feature as a means of detecting anomalous conditions as described above. By now, approximately 5000 cases have
been carried out in our Institute, the great majority producing a reliable diagnosis and resulting in a healthy birth. In virtually all cases, the exact anomalous chromosome can be identified and a decision taken as to whether the embryo should be transferred to its mother’s uterus or discarded. A by-product of this approach is to classify the embryos for its sex chromosomes, and so determine the sex of the resulting baby. This form of sex selection can be applied to discard embryos with sex-linked diseases, or to determine the sex of the offspring. It is applied for sex selection in many IVF clinics around the world, perhaps especially in India, although legislation is being passed to prevent its wider use which can result in an excess of male births. In early studies, conditions such as cystic fibrosis were analysed and carrier embryos could also be detected. Completion of the human genome will in future enable diagnosis of literally all disease genes to be achieved, and already 130 different genetic diseases have been successfully detected in human embryos. Diagnoses of mutants in tumour suppressor genes has led to the elimination of embryos carrying various cancer genes, and this has resulted in the cleaning-up of families with pedigrees for several cancers. Likewise, a programme in Cyprus, sustained by their government, has led to a succession of births free of β-thalassaemia, which is a frequent cause of early death in that country. Similar programmes may be established elsewhere, for example in relation to cystic fibrosis in Israel. Once again, approaching 1000 normal births have been achieved via this approach to PGD, and our thoughts are
Ethics, Law and Moral Philosophy of Reproductive Biomedicine, Vol. 2, No. 1, February 2007 © 2007 Published by Reproductive Healthcare Ltd, Duck End Farm, Dry Drayton, Cambridge CB23 8DB, UK
Ethics of PGD - Y Verlinsky
turning to diagnoses of diseases with genetic predisposition or to epigenetic factors as a cause of inherited disease. This approach to PGD can also be used to ensure that fresh samples of embryo stem cells are free of genetic disorders, or carry specific mutations, in order to establish long-term cell lines for analysis (Verlinsky et al., 2005). In the first meeting of this series, I concentrated on the current situation regarding designer babies, which involves treatments for individuals who have a serious illness, e.g. Fanconi anaemia, and are threatened with early death, by ‘designing’ their future siblings (Verlinsky et al., 2000, 2001, 2004, 2005). The mother wished to save her first-born and have a second pregnancy with a child free of disease. PGD was thus applied to identify her new embryos free of the disease, and also to classify their HLA types so that the new child’s umbilical stem cells could be collected and successfully grafted to the first-born child to cure its Fanconi anaemia. This procedure is often referred to as ‘preimplantation HLA typing’, ‘designer babies’ or ‘saviour babies’ and has proved to be remarkably successful. Care is needed to ensure that an embryo being used to form the second child has been thoroughly analysed to ensure it is free of Fanconi anaemia and that its HLA types match those of the recipient. Under these circumstances, umbilical cord blood cells from the second child were grafted to the first-born child to ensure it no longer has the disease. The technique has proved to be very successful in mending Fanconi anaemia and other genetic diseases in the first-born child some years after birth. Various other disease conditions have been treated in our clinic, and over 30 babies free of inherited disease and HLA matched to the affected siblings have been born.
2EFERENCES Verlinsky Y 2005 Designing babies: what the future holds. Reproductive BioMedicine Online 10 (Suppl. 1) 24–26. Verlinsky Y, Strelchenko N, Rechitsky S et al. 2005 Human embryonic stem cell lines with genetic disorders. Reproductive BioMedicine Online 10, 105–110. Verlinsky Y, Rechitsky S, Sharapova T et al. 2004 Preimplantation HLA typing. Journal of the American Medical Association 291, 2079–2085. Verlinsky Y, Rechitsky S, Schoolcraft W et al. 2001 Preimplantation diagnosis for Fanconi anemia combined with HLA matching. Journal of American Medical Association 285, 3130–3133. Verlinsky Y, Rechitsky S, Schoolcraft W 2000 Designer babies – are they a reality yet? Case report: Simultaneous preimplantation genetic diagnosis for Fanconi anaemia and HLA typing for cord blood transplantation. Reproductive BioMedicine Online 1, 31.
Received 27 October 2006; accepted 31 October 2006.
This brief report is meant as a basis for discussion. PGD is spreading wider, although in some countries many clinics are primarily concerned with sex selection, which may be made illegal. Ethical Committees are essential when practising PGD since problems can emerge when choosing embryos for transfer. For example, at the London meeting, demonstrations against PGD as a eugenic approach to the alleviation of deafness were made by protesters who wished to transfer embryos carrying deafness genes since the parents wished to raise deaf children who would fit into their existing family of deaf children. This situation also raises major ethical matters such as who should decide whether to transfer normal or affected embryos to the mother, and whether a doctor is compelled to accept a parental decision to transfer the afflicted embryos and discard those free of disease.
Ethics, Law and Moral Philosophy of Reproductive Biomedicine, Vol. 2, No. 1, February 2007
%THICS OF PREIMPLANTATION GENETIC DIAGNOSIS $R 9URY 6ERLINSKY IS A GRADUATE POST GRADUATE AND 0H$ OF +HARKOV 5NIVERSITY IN THE FORMER 5332 (IS RESEARCH INTERESTS INCLUDE CYTOGENETICS EMBRYOLOGY AND PRENATAL AND PREIMPLANTATION GENETICS (E INTRODUCED POLAR BODY TESTING FOR PREIMPLANTATION GENETIC DIAGNOSIS AND DEVELOPED THE METHODS FOR KARYOTYPING SECOND POLAR BODY AND INDIVIDUAL BLASTOMERES (E HAS PUBLISHED OVER PAPERS AS WELL AS THREE BOOKS ON PREIMPLANTATION GENETICS
$R 9URY 6ERLINSKY 9URY 6ERLINSKY 2EPRODUCTIVE 'ENETICS )NSTITUTE .ORTH (ALSTED 3TREET #HICAGO ), 53! #ORRESPONDENCE E MAIL RGI FLASHNET
!BSTRACT This paper briefly reviews the current status of preimplantation genetic diagnosis (PGD), to offer a basis for discussion about its ethical background. It describes the situation regarding modern types of PGD, which involve analyses on the inheritance by human embryos of chromosomal disorders or gene mutations. The current scale of these treatments is discussed, together with the progress of new advances such as ‘designer babies’. Brief reference is made to the first meeting in this series. Keywords: designer babies, ethics, preimplantation genetic diagnosis
)NTRODUCTION It is a pleasure to speak to this conference. My topic today concerns the application of preimplantation genetic diagnosis (PGD) to the study of deleterious gene mutations in an embryo or the analysis of its chromosomal complement in order to select those embryos which are diploid for transfer to their mother. Embryos carrying these defects are identified by excising a single blastomere which enables their chromosomal complement by means of fluorescent in-situ hybridization (FISH). If needed, a second biopsy can be performed at the blastocyst stage to corroborate the first diagnosis or to check the possibility of mosaicism in the embryo. A few thousands of babies have already been born, with approximately 1000 involving gene diagnosis and the rest chromosomal diagnosis. Diagnoses can also be achieved in many cases by excising and diagnosing the first and second polar bodies to gain information on the oocyte genotype. The results of this work were discussed in my earlier contribution to the London meeting on Moral Philosophy and Assisted Reproduction (Verlinsky, 2005), and some specific aspects of these treatments will be outlined in this paper.
It has become very evident over the last decade that an extraordinarily high proportion of human embryos are chromosomally abnormal. These effects range from monosomy and trisomy to various forms of polyploidy, translocations, deletions and other genetic defects. This approach to assessing embryos by chromosomal analyses is becoming a regular feature as a means of detecting anomalous conditions as described above. By now, approximately 5000 cases have
been carried out in our Institute, the great majority producing a reliable diagnosis and resulting in a healthy birth. In virtually all cases, the exact anomalous chromosome can be identified and a decision taken as to whether the embryo should be transferred to its mother’s uterus or discarded. A by-product of this approach is to classify the embryos for its sex chromosomes, and so determine the sex of the resulting baby. This form of sex selection can be applied to discard embryos with sex-linked diseases, or to determine the sex of the offspring. It is applied for sex selection in many IVF clinics around the world, perhaps especially in India, although legislation is being passed to prevent its wider use which can result in an excess of male births. In early studies, conditions such as cystic fibrosis were analysed and carrier embryos could also be detected. Completion of the human genome will in future enable diagnosis of literally all disease genes to be achieved, and already 130 different genetic diseases have been successfully detected in human embryos. Diagnoses of mutants in tumour suppressor genes has led to the elimination of embryos carrying various cancer genes, and this has resulted in the cleaning-up of families with pedigrees for several cancers. Likewise, a programme in Cyprus, sustained by their government, has led to a succession of births free of β-thalassaemia, which is a frequent cause of early death in that country. Similar programmes may be established elsewhere, for example in relation to cystic fibrosis in Israel. Once again, approaching 1000 normal births have been achieved via this approach to PGD, and our thoughts are
Ethics, Law and Moral Philosophy of Reproductive Biomedicine, Vol. 2, No. 1, February 2007 © 2007 Published by Reproductive Healthcare Ltd, Duck End Farm, Dry Drayton, Cambridge CB23 8DB, UK
Ethics of PGD - Y Verlinsky
turning to diagnoses of diseases with genetic predisposition or to epigenetic factors as a cause of inherited disease. This approach to PGD can also be used to ensure that fresh samples of embryo stem cells are free of genetic disorders, or carry specific mutations, in order to establish long-term cell lines for analysis (Verlinsky et al., 2005). In the first meeting of this series, I concentrated on the current situation regarding designer babies, which involves treatments for individuals who have a serious illness, e.g. Fanconi anaemia, and are threatened with early death, by ‘designing’ their future siblings (Verlinsky et al., 2000, 2001, 2004, 2005). The mother wished to save her first-born and have a second pregnancy with a child free of disease. PGD was thus applied to identify her new embryos free of the disease, and also to classify their HLA types so that the new child’s umbilical stem cells could be collected and successfully grafted to the first-born child to cure its Fanconi anaemia. This procedure is often referred to as ‘preimplantation HLA typing’, ‘designer babies’ or ‘saviour babies’ and has proved to be remarkably successful. Care is needed to ensure that an embryo being used to form the second child has been thoroughly analysed to ensure it is free of Fanconi anaemia and that its HLA types match those of the recipient. Under these circumstances, umbilical cord blood cells from the second child were grafted to the first-born child to ensure it no longer has the disease. The technique has proved to be very successful in mending Fanconi anaemia and other genetic diseases in the first-born child some years after birth. Various other disease conditions have been treated in our clinic, and over 30 babies free of inherited disease and HLA matched to the affected siblings have been born.
2EFERENCES Verlinsky Y 2005 Designing babies: what the future holds. Reproductive BioMedicine Online 10 (Suppl. 1) 24–26. Verlinsky Y, Strelchenko N, Rechitsky S et al. 2005 Human embryonic stem cell lines with genetic disorders. Reproductive BioMedicine Online 10, 105–110. Verlinsky Y, Rechitsky S, Sharapova T et al. 2004 Preimplantation HLA typing. Journal of the American Medical Association 291, 2079–2085. Verlinsky Y, Rechitsky S, Schoolcraft W et al. 2001 Preimplantation diagnosis for Fanconi anemia combined with HLA matching. Journal of American Medical Association 285, 3130–3133. Verlinsky Y, Rechitsky S, Schoolcraft W 2000 Designer babies – are they a reality yet? Case report: Simultaneous preimplantation genetic diagnosis for Fanconi anaemia and HLA typing for cord blood transplantation. Reproductive BioMedicine Online 1, 31.
Received 27 October 2006; accepted 31 October 2006.
This brief report is meant as a basis for discussion. PGD is spreading wider, although in some countries many clinics are primarily concerned with sex selection, which may be made illegal. Ethical Committees are essential when practising PGD since problems can emerge when choosing embryos for transfer. For example, at the London meeting, demonstrations against PGD as a eugenic approach to the alleviation of deafness were made by protesters who wished to transfer embryos carrying deafness genes since the parents wished to raise deaf children who would fit into their existing family of deaf children. This situation also raises major ethical matters such as who should decide whether to transfer normal or affected embryos to the mother, and whether a doctor is compelled to accept a parental decision to transfer the afflicted embryos and discard those free of disease.
Ethics, Law and Moral Philosophy of Reproductive Biomedicine, Vol. 2, No. 1, February 2007