Professor Tim Lewens challenges the human genome’s unique place in bioethics
Tim Lewens was always going to be a scientist. That is, until a gap year spent reading philosophy books left him with cold feet. He switched to philosophy during his first week at university, but immediately feared he had made a huge mistake leaving science behind. “Philosophy of science turned out to be a really fortuitous thing for me,” says Lewens, now a professor of the subject at the University of Cambridge, UK.“It was exactly what I would have aimed at doing, had I known it existed!”
In February, he gave a Science and Society talk at EMBL Heidelberg entitled ‘Blurring the germline – from genome editing to transgenerational epigenetic inheritance’. In the talk, Lewens highlighted the special form of ethical concern that surrounds making heritable changes to the human genome. He then explored other heritable changes to human germline cells – cells that pass on their characteristics to offspring – suggesting that the genome should be just one part of a wider discussion about how we make decisions that impact future generations.
Institutions around the world have differing stances on intentionally editing germline cells. The UNESCO International Bioethics Committee says “interventions on the human genome should be admitted only for preventive, diagnostic or therapeutic reasons and without enacting modifications for descendants”.1By contrast, the US National Institutes of Health “will not fund any use of gene-editing technologies in human embryos”,2 whether those alterations are heritable or not. In the UK, however, one form of heritable germline modification – mitochondrial donation – has been legal since 2014.
What are mitochondria?
Mitochondria are specialised components of most eukaryotic cells – cells that have a nucleus bound by a membrane. They convert the chemical energy gained from food into a form cells can use: adenosine triphosphate. Mitochondria are thought to have originated as free-living bacteria that were incorporated into larger eukaryotic cells around two billion years ago. There they formed a symbiotic relationship, providing energy in exchange for protection.
Due to their origins as organisms in their own right, mitochondria in human cells have their own DNA – a genome of 37 genes. Over time, many genes essential for mitochondrial function have migrated to the cell’s nucleus. Mitochondria are typically passed only from mother to child, since there are many more mitochondria in egg cells than in sperm cells, and in many species there are mechanisms to destroy paternal mitochondria that enter the egg cell.
Defects in the mitochondrial DNA of a woman’s egg cell can lead to a range of systemic diseases that can be fatal for her children. Women in the UK can have the nucleus of their fertilised egg cell placed inside the cell of a donor which has had its nucleus removed. All cells in the resulting embryo will have the mother’s nuclear DNA, but the donor’s functioning mitochondrial DNA. Not only will the child be disease free, but they will pass on the donated, healthy mitochondrial DNA to their own offspring: an inherited, and likely irreversible, germline modification.
This treatment is possible because the UK Department of Health decided that “genetic modification involves germline modification of nuclear DNA that can be passed on to future generations”.3 Therefore, in the case of specific techniques that have had their safety thoroughly tested and which remain subject to strict, ongoing regimes of regulatory approval, editing mitochondrial DNA is legal.
We’re often not even sure what the criterion is, let alone if we can be confident whether or not we’ve achieved it!
However, very similar diseases caused by faulty genes inside the nucleus, rather than the mitochondria, cannot be legally treated by gene editing. Lewens argues that, because of cases like these, altering the nuclear genetic code should not necessarily constitute an immovable ethical line. Rather, genuine concerns over editing the human genome should fall into the wider framework of how we balance the needs and risks associated with any decisions that affect future generations.
In some cases, we may never know for sure if the decisions we make are the right ones. “Consider Fred, a man living fifty years in the future,” says Lewens, in our interview after his talk. “Is his life better or worse because we used some controversial technology now? Well, if we hadn’t, then the same Fred simply wouldn’t exist.” Should we care about some less personal, average wellbeing per capita then? “In that case, it would be best to have just a few people who were all super happy!” As Lewens puts it, when it comes to measuring the success of our decisions, “We’re often not even sure what the criterion is, let alone if we can be confident whether or not we’ve achieved it!”
Risk and reward
Instead, Lewens argues, we should focus on the present and look at factors such as whether there are ways to achieve similar benefits to a new biological technology with less risk. “In general, if you look at why people’s health fails,” says Lewens, “it can be due to well-understood but hard-to-action problems: people not eating the right kinds of food or not doing enough exercise, poor patient data-processing in hospitals, etc. In some cases, new technologies might not provide the best solutions.”
This is one part of Lewens’ wider ethical framework for assessing the risks for future generations. “In ethical deliberations,” he says, “it’s often not worth trying to build your argument upwards from your foundational beliefs [e.g. all gene editing is right or wrong], because the next person probably won’t agree with them.” Instead, he tells me, the most important factors are compassion and open discussion, taking into account as many opinions as possible and carefully measuring benefits, costs and risks. “When any new technology has costs and benefits, it’s sensible not just to make sure the benefits outweigh the costs, but that the people who suffer most from the costs gain the most from the benefits too.”
The nucleus of this cell fluoresces in bright green thanks to GFP-labelled nucleoporin proteins. EMBL scientists use engineered nucleoporins as 3D reference standards to improve super-resolution microscopy.