Should we stop manipulating the human germline?

In China, the new CRISPR/Cas method has been used to manipulate the human germline for research purposes. But shouldn’t researchers everywhere respect the human germline until more is known about the possible ramifications? Stem cell researcher Dieter Egli and bioethicist Anna Deplazes Zemp discuss this question for Horizons.

(From "Horizons" no. 107, December 2015)

No – says the stem-cell researcher Dieter Egli.

Genetically modifying the germline is banned today in Switzerland and in many other countries. We know almost nothing about the efficacy and the safety of such interventions, and still less about the long-term effects – intended or otherwise. The experiments with human embryos in China demonstrate just how crude the technology still is. Only in four of 86 cases did the genetic manipulation succeed on a molecular level, and even they were only partially successful. Most of them displayed genetic abnormalities. On the basis of these results, we shouldn’t expect to be applying this technique in the near future.

On the other hand, humans suffer from many genetically determined diseases, and we are constantly uncovering more of the genetic causes. How are we supposed to fight these? One possibility is pre-implantation diagnostics. The Swiss federal parliament would like to allow its use in certain cases. Pre-implantation diagnostics – in other words, examining the embryo before it is implanted in the mother – cannot always prevent disease. There’s little to be done, for example, if both partners carry the same genetic defect or if several genetic defects are present at the same time. Another possibility, which we should consider in this light, is a genetic correction to the germline.

We have to learn how effectively and how safely we can manipulate genes in the human germline, and we have to find out whether this is better than other therapies. It’s a contradiction in terms to demand that we wait until we know more, yet at the same time to place a moratorium on research. If we want to know more, we have to carry out research. We shouldn’t put a brake on it, but promote it within a basic set of conditions. For example, it could be restricted to research for the purpose of healing diseases.

Would this mean opening up a doorway to the genetic improvement of human beings, like some people fear and others hope? I’m convinced that humankind has to face up to such questions, and that we have to regulate the application of these technologies. These discussions are necessary, and they will be all the more successful, the better we know the possibilities and the boundaries of manipulating the germline.

Yes – says the bioethicist Anna Deplazes Zemp.

The CRISPR/Cas method allows us to carry out far more precise, less risky manipulations of the human germline than any other technology. But even if the efficacy of this technique can still be improved, there remain risks such as undesirable integration and the emergence of genetic mosaics. So we are faced with the question: should countries such as Switzerland now lift their ban on manipulations of the germline, or should we renounce such experiments all over the world? I’m in favour of the latter option.

Genetic modifications to the human germline affect the development process and every cell of the developing human individual. Furthermore, these changes are passed down to future generations. Are we really ready to take on the responsibility for the genetic profile not just of the emerging individual human being, but also for his or her descendants?

We have to be aware that transhumanists dream not just of healing illnesses by technological means, but also of improving the human race. People could use CRISPR/Cas to try and achieve such inheritable ‘improvements’. Before using this technique in the human germline, it must first be clarified how we are going to deal with such aspirations.

This has to be a global discourse. And trying to achieve that is a very ambitious goal. Representatives of different cultures have different opinions regarding experiments on human germ cells and embryos. We’ve already had a foretaste of this in the discussions surrounding the experiments by the Chinese group. They manipulated human embryos using the CRISPR/Cas technique, and their experiments were largely criticised in Western, Christian cultures. And yet, for ethical reasons, these experiments were carried out on embryos that were incapable of further development. So even the researchers themselves seem to think that their experiments would be problematical if they were carried out on embryos that could actually develop. This could perhaps provide us with a basis for a global consensus.

Dieter Egli is an assistant professor at Columbia University in New York. He took his doctorate at the University of Zurich and has carried out research into therapeutic cloning.

Anna Deplazes Zemp possesses a doctorate in molecular biology and works at the Institute for Biomedical Ethics and History of Medicine of the University of Zurich. Her current research includes working on the ethics project of the National Centre of Competence in Research ‘Molecular Systems Engineering’.