‘As the days seep their light, and we are drawn from the swell of summer, I often come to think of things. Like walking across sand, the ground beneath us feels at times so uncertain. We shift. In our careers, in our social relations, in the places we call home. Yet we place certainty in the knowledge that our lives have never been so prosperous. The steps that we took to get here – agriculture, the scientific method, industry, and now genetic modification – have resulted in profound change and have assigned many of our ailments to the past. You could say that we have become a gene based society, with our DNA the defining currency upon which we live. It is everywhere; in the holographic adverts presenting further ideals for which we should all strive, in the waving of our genetic data as the flag of our personhood, and the decisions our parents took to eliminate future health risks. It is amazing – so many lives have been saved that otherwise would have not. But uncertainty still remains. Are we really ultimately defined by our DNA as the world around would suggest or is there more…to being human?’
Written by: Ronan McCabe, Tatiana Álvarez Giovannucci
Genetics holds such pre-eminence that its reach has surpassed the realms of science and entered into our cultural references by featuring in science fiction productions, futuristic novels and being part of the current philosophical and ethical discourse. The focus is on the genetic modification of humans and the uses of our genetic information. Like the diary entry above, through such avenues as science-fiction we explore our fears and aspirations for the future. It may be the dystopian world envisaged in the film GATTACA or the more egalitarian-anarchistic-utopian world of an Iain M. Banks novel. But while these often strike us as over the top and unrealistic, are there any important truths to behold?
Humans have shaped their environment to their wants and needs through the use of genetics since early history, most obviously in the selective breeding of plants. The natural laws behind this were obscure until the nineteenth century, when Gregor Mendel discovered the concept of inheritance, giving birth to the study of genetics. The field has developed greatly since then, and modern advancements hold the promise that we can treat and even eliminate genetic disease.
One of the most exciting research tools at present is the CRISPR/Cas technology. Derived from a cellular mechanism found in prokaryotic organisms, it allows researchers to study the implication of any gene of interest in any particular biological system through ‘knock-out’, or deletion of the gene. It is hoped that this will eventually be used in a clinical setting. The idea would be to address monogenic diseases (e.g. Huntington’s and cystic fibrosis) through deleting/replacing the single causal gene in the human embryo. However, this hope has yet to be realised and has been hindered by, among others, the presence of off-target effects. In addition, some researchers question whether CRISPR is really the solution for monogenic diseases. “The simpler solution would be to do in vitro fertilisation and then select [a healthy embryo]. It is done already. It does not completely eradicate disease, but neither would editing: only a few people will be able to afford it, or would like to do it,” says Sten Linnarsson, professor of Molecular Systems Biology at KI. Here he refers to preimplantation genetic diagnosis (PGD), a technique established in the 90s to help couples with a high risk of conceiving a child with a severe genetic disease. They require an oocyte biopsy, followed by in vitro fertilization (IVF) and embryo screening.
With our current knowledge it is hard to envisage such genetic technology being extended to clinically treat more complex diseases – which may involve gene-gene and gene-environment interactions – in the immediate future. The use of genetically-modified human embryos in research also raises serious ethical considerations. This is highlighted by the restriction in place here in Sweden with the Genetic Integrity Act (see BOX 1), which states that human embryos can only be used for a fourteen day period after which they must be destroyed.
Perhaps not capturing the imagination to the same extent, the use of genetic data confers the most immediate clinical benefit. Biobanks are a noticeable example. These banks hold biological samples, with individual samples numbering in the 100’000s. Such a huge sample size has massively amplified the capacity and power of research into the genetic components of certain diseases and allows for the identification of biomarkers for disease.
Suppose we have the power to choose people’s genetic characteristics. Once we have eliminated genetic defects, what, if anything, should we do with this power?’ Jonathan Glover (What sort of people should it be?, 1984)
If safe enough, not using tools that would avoid suffering would be unethical. However, the possibility that the use of genetics exceeds the domains of science raises some chilling prospects. These are exemplified in movies like GATTACA (1997), taking place in a dystopian future in which natural conception is replaced by IVF and PGD for embryo selection. Consequently, the correction of genetic imperfections has become routine, and genetic rather than moral excellence determines a person’s worth. Niklas Juth, an ethics researcher at KI, tells us that it is not far-fetched that a ‘class society’ may form where our genetic constitution is known and used by employers, spouses etc. But rather than this being driven through state policy, as has previously been the case and how it is described in most sci-fi scenarios, Niklas states that “it is more plausible to imagine that it will be, so to speak, on the market arena” leading to the worrying scenario of ‘back-door eugenics’ (see BOX 2).
Thankfully, there are protections against the misuse of genetic data beyond the clinical setting. Niklas explains that the previously mentioned Swedish Genetic Integrity Act “states that genetic information may not be used to the detriment of individuals.” And while there are some exemptions made for insurance companies who stand to make significant economic losses, they only “are allowed to ask for genetic information that you already have, they are not allowed to force you to get new genetic information.”
Fredrik Lanner, assistant professor at KI studying human embryonic development, believes that society will be able to successfully regulate new genetic technologies. In an interview in the magazine Medicinsk Vetenskap, he points out that embryo screening by IVF and PGD are nowadays established techniques in use only to avoid serious diseases, not for selecting embryos by any other genetic trait. “I think that society will be able to deal with the issue of how CRISPR should be used just as well,” he remarks. “I think the UK is a good role model,” says Niklas Juth, referring to the public discussions and governmental investigations that led to the legalisation of mitochondrial DNA transfer in 2015.
What is it that scares us about genetic modification?
In the context of biotechnology, the generation and use of genetically modified organisms (GMOs) has expanded. Most of the concerns regarding GMOs tackle health-related consequences of their consumption, or the interference with environmental processes. However, GMOs do not seem to challenge the identity of the organism in question: wheat modified to resist better plagues or droughts, continues being wheat, right? But when the same line of thought is applied to humans, it creates some feeling of uncertainty. Are we perhaps afraid that genetic modification challenges our own identity?
This concern is not universal, though. The transhumanist movement believes that the advances in genetics can be employed, together with other technical developments, to enhance human capabilities. In the future, we might be able to overcome some of our ‘flaws’: low physical endurance, aging, even mortality.
Niklas Juth believes that currently, the use of gene editing for enhancing human capabilities should not be performed. “We don’t know enough. So the potential benefits – which are very uncertain – would not yet at least outpace the potential risks.” However, he argues that the alarm that human enhancement generates is unfounded. “Who really is in principle against enhancement? And why? We try to enhance the capabilities of our children by different means: by practising and education, etc. So why shouldn’t we do it by genetic means if we can?.”
Gemma Marfany, geneticist and member of the Observatory of Bioethics and Law at the University of Barcelona, thinks that genetic modification should not be considered as dehumanizing, but puts into question the usefulness of the transhumanist goal. “I do not foresee that lengthening our lives, being stronger or thinking faster will make us in any way happier. And certainly, there is no way that we could be immortals. As a biologist, I believe this is an oxymoron type of issue: we live therefore we die.”
All he’d wanted were the same answers the rest of us want. Where did I come from? Where am I going? How long have I got?’ (Blade Runner, 1982)
MISUNDERSTANDING GENETIC DATA
DNA provides some answers to these questions. Follow your mitochondrial DNA and you will get an unbroken lineage going back to the first women migrating out of Africa. DNA certainly cannot tell you how your career prospects look like, but it can give you some probabilities about your future health status, which generally creates more angst: will I develop cancer? Or diabetes? Intimidating questions to which the answer, we are told, lies in our DNA. This idea has boosted the success of direct-to-consumer genetic testing companies, like 23andMe or AncestryDNA. As easy as spitting into a tube, you can get all sorts of information about your ancestry, health markers, or even find out about unknown relatives.
There are discordant opinions on the value, or even morality, of these tests. On one side, worried voices claim that these tests have the potential to do more harm than good. You may argue that by knowing your risk for, for example diabetes, you might be able to adjust your lifestyle to prevent it. But would we? “You might as well react the other way around,” Niklas Juth points out. “If it [the test] says I got this huge risk of diabetes I might as well have as much fun as I can and eat more cake.” On the other side, there is enthusiasm about the empowerment of society. “People should have the power to collect this information and use it, and I think they will be able to handle it,” says Sten Linnarsson. He believes that we tend to exaggerate how useful DNA data actually is. And that’s said from experience. “Most of the information was useless,” he concludes from his own genetic data (part of it publicly available on his lab website). Nevertheless, genetic data is of great use in science and healthcare. Sten predicts that as the costs plummet, DNA sequencing will fully integrate in the medical practice: not as a way to diagnose, but to be performed ubiquitously. This means that the amount of sensitive data handled by the healthcare system could eventually become a burden, a problem that Sten believes will not occur: “As the cost plummets, it also means that it would actually be more convenient and cheaper to just do it again next time. You then not even need to store it… we might get closer to a GATTACA type of scenario, right?”, alluding to the ease and speed at which genome sequencing is performed in this movie.
If a systems biologist could not extract much out of his genome… Can we? There are basically two kinds of genetic information. There is the monogenic kind of data – you have a mutation that will unambiguously result in a disease, but most of these diseases are actually very rare. Our big worries – cancer, diabetes, mental illness – are of the multifactorial kind, with many genes involved and, importantly but often forgotten in the media, environmental factors. The field of epigenetics tries to address these complex interactions by studying how external cues influence gene expression and inheritance without modifying the DNA sequence (e.g. through DNA methylation). So the problem with the multifactorial data is that we tend to overestimate the genetic contribution. “Because the translation from DNA to disease, or to happiness or to fitness or whatever… we just don’t know how to do this translation,” remarks Sten Linnarsson.
Niklas Juth identifies the same tendency to overemphasize the value of genetic data, and describes what he calls ‘genetic exceptionalism’: the idea that, opposed to other medical data, there is something special about DNA. He stresses that the characteristics that might make genetic information special – that it is transmittable, that it is shared to big extent between relatives, and that it is sensitive – are shared with other non-genetic information, as exemplified by the case of a child with congenital syphilis: a disease that is not genetic but transmittable to offspring, tells about the mother and the child, and is certainly sensitive.
Perhaps scientists should focus on bringing awareness of what the limits of DNA information are and how to interpret the data. Because what we don’t understand we cannot control – a vulnerability that could be exploited for commercial purposes.
The rise of a genetic social network?
Although DNA may not be as special as we might think, it is still sensitive data. And as such, its unauthorized use could affect the person’s wellbeing or violate his/her privacy. Despite of being carefully safeguarded by law, the way big data companies use our non-genetic sensitive data is already an ongoing issue. “The issue here is when, how, why for and who will be interested in analyzing our genetic information,” says Gemma Marfany. Niklas Juth also shows some concerns about the commercialization of genetic testing, as it challenges the needs-first basis of the healthcare system: when healthcare products require out of pocket payments, the more money you have, as opposed to need, the greater your access.
Sten Linnarsson, on the contrary, believes commercialization itself is not a problem, but that we should perhaps adopt a protectionist approach in the regulation of these companies to avoid the generation of big monopolies. “If 23andMe and any other company has the DNA [sequence] of everybody and can cross reference this, that would be dangerous.” New regulations like the EU Data Protection Reform (see BOX 3) aim to give more control to people over their sensitive data, also covering genetic data. Will these regulations be enough? We will have to see.
Diary Entry 3/12/2107
‘Our story is an interesting one indeed. From our modest hunter-gatherer beginnings to the Anthropocene, and everything that happened in between – splitting the atom, the genetic revolution etc. But looking back, I am not so sure our present selves are much different. I think we just came to truly realise what had always been the case: we are a social species and we live within biological systems, not above or beyond them. It seems so simple. But it has been so powerful, in that it has guided the latest part of our story. And after many thousands of years, perhaps we can finally say that our story is heading in a direction that works for us all.’
The Genetic Integrity Act (2006:351)
A compilation of several laws restricting the use of certain technologies in order to safeguard the integrity of the individual. The Act regulates the use for medical purposes only of prenatal and preimplantation genetic diagnosis, puts in place measures for research or treatments using human eggs. It also includes measures to safeguard the privacy of the individual, regarding the use of genetic investigations and genetic information. Lastly, the Act also contains provisions on criminal liability for trade in human biological material.
Eugenics as a political concept reached its height in the beginning of the 20th century. Many states adopted policies to ‘improve’ their population’s genetics and were characterised by unsavoury acts of discrimination and even forced sterilisation. Needless to say, today we would understand this to be in complete breach of human rights.
Reform of data protection rules in the EU
The objective of this new set of rules is to give citizens back control over their personal data. The reform entered into force in 2016, and from the 6th May of 2018 it should enter into the national laws of all EU Member States. By these rules, the individual should give consent for any information collected, and have access to it at any time. The data should be stored with special security
This article was previously published in Medicor 2017 #4
Edited by: Joanne Bakker