I am about to watch a film called “Errors of the human body” that I just ran into at the local Scope charity shop. Although I don’t know yet how much relevance it has within the context of the new eugenics, it reminds me of (the graphics for) a session on 17 October I saw announced on Twitter this afternoon:
Friends in TO come join me Thursday, October 17, 6:00-8:00 pm The Fields Institute for Research in Mathematical Sciences
“Altered Inheritance: extinction, recreation or transformation?
a dialogue and discussion on the implications of genome editing on humans and other organisms” pic.twitter.com/8VStrWi9yT
The use of CRISPR (pronounced “crisper”) to modify human embryos has prompted a healthy debate on the ethics of human genetic technologies. This tool is controversial, in part, because changes that are made to the embryo could be passed down to future generations. Niakan’s recent research is novel, and less ethically fraught than some other genome-editing research.
Research labs around the world are using CRISPR to selectively insert, delete or replace DNA with far greater precision and at a lower cost than other genome-editing techniques. Since 2015, five reports have detailed its use in human embryos to correct disease-causing mutations or create resistance to infectious disease.
The project led by Niakan had a starkly different aim. It used CRISPR to peek at the earliest stages of human embryonic development by targeting a gene called OCT4, which is active in the cells that go on to form the embryo.
Niakan’s immediate objective was to better understand the early aspects of human development. But her research eventually may help reveal why some pregnancies end in miscarriages and may improve the success of in vitro fertilization.
Much of the global discussion over the ethics of modifying human embryos has focused on whether the technique might be unsafe or used for non-medical purposes. Niakan’s recent project brings other aspects of this debate to light. How do scientists acquire the embryos they use in their research, and how are their projects approved?
So far, these types of experiments have been done in China, the United Kingdom and the United States. With only limited data available on the experiments conducted in China, it makes sense to focus the discussion on the experiments based in the United States and in the United Kingdom.
Who’s taking the risk – and why?
Earlier this year, Shoukhrat Mitalipov, a reproductive biologist at Oregon Health and Science University (OHSU), and his colleagues used CRISPR in human embryos to repair a mutation that causes heart disease. From an ethics standpoint, Mitalipov’s research is more controversial than Niakan’s. The goal of his experiments was to make changes to the human embryo that could be passed on to future generations. Niakan’s research, on the other hand, aimed to develop our understanding of human embryology.
To do the experiments, Mitalipov’s team had to create human embryos from donated eggs and sperm. In contrast, Niakan’s project used embryos that were left over from fertility treatments. This is an important difference.
For Mitalipov’s study, the women who donated their eggs for research were exposed to the risks associated with hormonal stimulation and egg retrieval. These risks include abdominal pain, vomiting, rapid weight gain, shortness of breath, and damage to the organs that are close to the ovaries. A particularly serious risk is ovarian hyperstimulation syndrome that can require hospitalization.
With Niakan’s study, women assumed these risks in connection with their IVF treatment, not their participation in research. These women weighed the potential harms of hormonal stimulation and egg retrieval against the potential benefits of having a child using assisted human reproduction. Embryos remaining after fertility treatment were donated to research.
It’s also worth examining how these studies were approved. Several committees, panels and review boards from OHSU provided input and guidance prior to granting Mitalipov permission to do his experiments. OHSU is Mitalipov’s home institution. This raises the spectre of institutional conflict of interest because OHSU stands to benefit from Mitalipov’s research if his work attracts more research funding or enhances the university’s reputation.
In the United Kingdom, the governance and oversight of human embryo research lies in the hands of authorities that are legally regulated and are at arms length to the institutions conducting the research. Ethics review of human embryo research occurs at both the national and regional level. The Human Fertilisation and Embryology Authority and the regional research ethics committee reviewed Niakan’s proposal before she could begin her experiments.
As genome editing of human embryos becomes more widespread, it is important to understand the differences between one project and the next so that we can meaningfully discuss the range of ethical, social, political and regulatory issues associated with the research.
Mitalipov’s team is not the first to genetically modify human embryos. This was first accomplished in 2015 by a group of Chinese scientists led by Junjiu Huang. Mitalipov’s team, however, may be the first to demonstrate basic safety and efficacy using the CRISPR technique.
This has serious implications for the ethics debate on human germline modification which involves inserting, deleting or replacing the DNA of human sperm, eggs or embryos to change the genes of future children.
Those who support human embryo research will argue that Mitalipov’s research to alter human embryos is ethically acceptable because the embryos were not allowed to develop beyond 14 days (the widely accepted international limit on human embryo research) and because the modified embryos were not used to initiate a pregnancy. They will also point to the future potential benefit of correcting defective genes that cause inherited disease.
This research is ethically controversial, however, because it is a clear step on the path to making heritable modifications – genetic changes that can be passed down through subsequent generations.
Beyond safety and efficacy
Internationally, UNESCO has called for a ban on human germline gene editing. And the “Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine” – the Oviedo Convention – specifies that “an intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants.”
In a move away from the positions taken by UNESCO and included in the Oviedo Convention, in 2015 the 12-person Organizing Committee of the first International Summit on Human Gene Editing (of which I was a member) issued a statement endorsing basic and preclinical gene editing research involving human embryos.
The statement further stipulated, however, that: “It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application.”
Mitalipov’s research aims to address the first condition about safety and efficacy. But what of the second condition which effectively recognizes that the human genome belongs to all of us and that it is not for scientists or other elites to decree what should or should not happen to it?
Since the 2015 statement was issued, many individuals and groups have tried to set aside the recommendation calling for a broad societal consensus.
For example, in February 2017, the U.S. National Academy of Sciences and National Academy of Medicine published a report endorsing germline modification. It states unequivocally that “clinical trials using heritable germline genome editing should be permitted” provided the research is only for compelling reasons and under strict oversight limiting uses of the technology to specified criteria.
Seeds of change in Canada
In Canada, it is illegal to modify human germ cells. Altering “the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants” is among the activities prohibited in the 2004 Assisted Human Reproduction Act.
Worried that “Canadian researchers may fall behind on the international scene” and that “restrictive research policies may lead to medical tourism,” the Canadian Institutes for Health Research (with input from the Canadian Stem Cell Network) has begun to plant the seeds of change.
In its Human Germline Gene Editing report, CIHR hints at the benefits of changing the legislation. It also suggests professional self-regulation and research funding guidelines could replace the current federal statutory prohibition.
Future of the species
With Mitalipov’s technological advances and increasing suggestions from researchers that heritable modifications to human embryos be permitted, it is essential that citizens be given opportunities to think through the ethical issues and to work towards broad societal consensus.
We are talking about nothing less than the future of the human species. No decisions about the modification of the germline should be made without broad societal consultation.