Genetic Engineering Requires a Heedful Eye

A Professional In Vitro Fertilisation Laboratory Microscope Closeup
by Mira C. Hasner, Leiden University Medical Centre
November 1, 2017

Long before discovery of DNA, humans have been strengthening traits in plants and animals through selective breeding. Aiming for useful variation, people started mutating genetic codes of plants in the 1960s. Since the 1970s, they have been inserting DNA in bacterial, plant and animal cells to study and to modify them. Engineered life has supplied many life-saving chemicals, such as clotting factors and insulin.[1] Twenty-first century genetic engineering uses techniques to modify and to manipulate organisms using processes of heredity and reproduction. Examples of artificial selection are artificial insemination, in vitro fertilization (IVF), cloning and gene manipulation.

Genetic knowledge enables manipulation and enhancement of human nature. Transgenic organisms and human gene sequences have been patented for clinical use, thus causing an enormous growth in biotechnology. Recent innovations have made it possible to remove and to replace unwanted genes, enhancing human genetic traits. But where will humanity draw the line once this is implemented in the healthcare system and becomes societal norm? If a child is immune to HIV, why not supply him/her with excellent eyesight and increased intelligence too? Genetic engineering prefers moulding nature over beholding nature, which is threatening to banish appreciation of life and its flaws.[2] Will the ethical barrier between curing and enhancing people be enough to prevent people from creating post-human species?

One of the newest developments in biotechnology is CRISPR-cas9. CRISPR stands for clustered regularly interspaced short palindromic repeats. It consists of short segments of repetitive prokaryotic DNA-codes, which can be seen as a huge DNA-library with built-in nucleotide fragments of an aggressive virus, called spacer DNA. Bacteriophages are viruses that attack bacteria by inserting its own DNA into cytoplasm, thus resulting in a take-over of protein- and DNA-synthesis. Cas9 are the RNA-guided DNA endonucleases that function as scissors in recognizing and cutting out viral DNA. Bacteria that survive this attack store the viral DNA in the CRISPR-library. Cas9 then scans the bacterial DNA for matches with the spacer DNA and destroys the recognized invading viruses. This mechanism is being applied to humans by making cas9 search for mutations and cut these out, after which a DNA-strand with functional sequences is implemented and taken up by the cell. This new technology holds the promise of a future in which genetic diseases can be cured and mutations of the human genome restored.

People have recently started exploring the possibilities of CRISPR-Cas9. In January 2013 Feng Zhang[3] published the first method of using CRISPR-cas9 to edit the genome of humans and mice. Molecular scissors engineered for site-specific modification of the genome give researchers the means to effectively analyse the genes, genomes and epigenomes. This could improve understanding of disease states and ease the process of developing new therapeutical applications. CRISPR-cas9 has been used to generate disease models to study genetic diseases, such as HIV, Duchenne muscular dystrophy, Haemophilia, Sickle-cell anaemia and β-thalassemia. Its possibilities promote future perspectives like cancer research with in vivo mutagenesis studies on animals, synthetic biology, a sgRNA library for drug targeting and induced pluripotent stem cell-therapy. Recent advances in genome editing with CRISPR have opened doors to application of gene therapy in the real clinic.[4] At this point CRISPR was seen as the big bang of genome editing technology by being a cost-effective, easy to administer alternative for previous platforms of genetic modification.

In 2015 researchers in China reported editing genes of human embryos in an attempt to make them resistant to HIV-infection.[5] This was only the second officially published claim of gene editing in human embryos. In 2017 they were followed by Americans, who corrected a pathogenic gene mutation in germline DNA responsible for hypertrophic cardiomyopathy in human embryos and avoidance of mosaicism in the edited embryos.[6] The changes caused by CRISPR are not inheritable unless the technique is used on reproductive cells or very early embryos. Be aware that this whispers of designer babies, which could lead to gradual but irreversible changes in the human gene pool. The consequences of changing heritable features in embryos for future generations could not possibly be overseen.

When science moves faster than moral understanding, it may overlook the consequences for people excluded during the transition, such as the elderly or those in lower social classes. Current generations were hardly aware of the technological digital revolution that was upon them, which has now changed the present and will impact the future permanently. Bostrom describes the phenomenon of anthropic shadow, an observation selection effect that prevents observers from perceiving certain kinds of catastrophes in their recent geological and evolutionary past. Catastrophe types that lie in the anthropic shadow are likely to be underestimated; therefore, light should be shed on them.

Though biotechnology is still in its early stages, most people worry less about the technological challenges these new developments are facing than the ethical concerns they raise. In the Netherlands, the Rathenau Institute conducted a public survey[7] on views of the general public on human enhancement in comparison to current treatments, such as cosmetic surgery or prescription of Ritalin. They assessed four main issues that unnerve the public. Firstly, people seem worried about safety, especially involving health risk and addiction. Social issues, such as peer pressure and fair access to enhancement resources, are another topic of concern. Peer pressure might be exerted upon people by emphasizing that it is unethical not to genetically modify embryos because it would disadvantage them, thus resulting in societal inequality. The public feels philosophical and ethical themes, such as luck and wellbeing, authenticity and identity, are at stake too. Finally, they are anxious about the shifting border between curing and augmenting human traits.

However, 90 per cent of the people in the United Kingdom, who learn their child will be born with Down’s syndrome, have an abortion nowadays.[8] In addition, IVF also grants the possibility to screen embryos prior to implantation. Through pre-selection or a change of health norms, genetically modified humans could become the new standard. As genetic diseases are eradicated, more and more people are likely to become pro human enhancement.

Transhumanists find humans not to be the pinnacle of evolution because they are limited in mental and physical abilities. These are aspects that can and should be improved according to Bostrom. They hope to become post-humans through human enhancement, providing them with longer and healthier lives. Transhumanists aspire to have better memory and intellectual abilities, more refined emotional experiences and, generally, to achieve a greater degree of control over their lives resulting in higher values, which unenhanced humans do not comprehend. They ask people to look at post-humanism in retrospect, through the eyes of post-humans instead of their own. Transhumanists recognize the dangers and negative consequences these developments may hold but do not see them as a decisive reason not to proceed. Nevertheless, they warn people to be aware of these “dystopian scenarios” and to take precautions.[9]

Posthumanists have thought of ways to counteract the inequality-increasing tendencies of enhancement technology, such as subsidizing it or providing it for free to lower social classes. However, there is no guarantee for implementation of such countermeasures in countries with a health care system based on market forces. Secondly, posthumanists claim to be able to reverse any adverse events the modifications might induce using the same technology. They conclude that every day the science is delayed is a crime against humanity because science is able to prevent people from suffering.

Kurzweil, a supporter of germline editing, has stated in a press conference that humanity is the only species that goes beyond its limitations. He says, “We did not stay in the caves; we did not stay on the planet; and we are not going to stay within the limitations of our biology.” In his singularity-based documentary, Kurzweil is quoted saying, “I think people are fooling themselves when they say they have accepted death.” His book, “The Singularity is Near,” adds to this, suggesting medical advances will allow science to make life expectancy limitless and to continuously repair and replace defective parts of the human body. He assumes the following step to somatic gene therapy is using this technology to replace human DNA with synthesized genes. Biologist P. Z. Myers has criticized Kurzweil’s predictions as being closer to the deluded religious movement of “New Age spiritualism” than to actual science and accuses him of not understanding basic biology.[10]

Fukuyama, a political scientist and sociologist, warns about the potential unknown costs of eradicating genetic illness. He fears the loss of other inherent human characteristics like intelligence or ambition. He further argues that humanity could lose the human essence that unites and distinguishes it from other animals, which he refers to as Factor X. Fukuyama calls for protection of this factor, which relies on a careful balance of moral choice, reason, sentience, emotion, dignity and consciousness. It grants people their right to be considered human and to be guaranteed certain human rights, such as life and security. Humans must not all be the same to have rights, but they should for equal rights. Using biotechnology to minimize suffering could go at the expense of people’s highest human qualities, such are compassion, resilience and overcoming weaknesses.[11]

“We have evolved to a state that resembles cancer:  a proliferation of the same cell type without taking in account organic laws of the whole. The same is being copied ceaselessly.” To the philosopher Baudrillard, alongside cloning, AIDS and viruses, cancer is a metaphor for everything that is happening within society. The result is an accumulation of roaming cells. Cells are depicted here as entities containing certain genetic information, which constantly gets passed on. In his future, the old problem of “love your close ones like yourself” is solved because the closest ones have become identical.[12] An important argument against germline editing is loss of the egalitarian genetic lottery, which results in large genetic variations between individuals narrowing down and clustering within certain social groups.

Successful people genetically embed their social advantages and increase disparity between the top and bottom of the social hierarchy. Those who are genetically modified may lose sympathy for those who are not by thanking their own enhancements to conscious choices rather than a result of the genetic lottery.11 Nietszche stated that if there is a continuum of gradations between human and nonhuman, there is within the type of human as well. According to him, the ordinary man is unable to relinquish his advantage. The thought of a purpose and self-benefit outperforms ordinary instincts. [13]

People are right to worry about the unpredictable societal and biological consequences of editing the human genome. However, banning technological research in this field would only mean loss of oversight on scientific development. Only by participating can humanity make sure further research is guided by caution, reason and transparency. Participation also includes support of the general public, for which a guarantee of safety is required.

Jean-Jacques Rousseau wrote, “The first man, who having fenced in a piece of land, said ‘This is mine’ and found people naïve enough to believe him, was the true founder of civil society.” But how are property rights applied to tissues and cells or the genetic DNA of cells themselves? Control over one’s body remains intact as long as the cells are attached to you. When cells are no longer inside your body, everyone could have property rights over them or intellectual property rights in innovations related to information contained therein. Past examples of patients whose cell lines were used for technological research without their knowledge or consent are Henrietta Lacks (HeLa)[14] and John Moore[15]. Scientists have grown more than two million HeLa-cells used in more than 11,000 patents. It is estimated that they cover millions of dollars worth of biological research. However, the patients will not profit from this. John Moore lost a property rights battle regarding an anti-cancer drug derived from his splenic cells, after which he started a campaign for patients’ rights.

Currently, the life sciences are experiencing a crisis in public perception of their work involving distrust and misunderstanding. There is a growing inaccessibility of science and technology, and ethical issues are being resolved within the sciences with a pragmatic and policy-oriented outcome. However, BioArt enables the public and humanities to participate in the debate of what values underpin scientific decisions by culturally embedding science. It uses the same materials, tools and technologies as life scientists. It encompasses results of life sciences and the expectations and fears of it. It serves as a social intervention, contributing to public discussion as a mediator and aspires to stimulate a new and more productive relationship between humanities and science where artists’ practice can be an integral part of scientific reflection.[16]

One example of BioArt challenging the public to consider its responsibility for transgenic beings is a project by Eduardo Kac in collaboration with French geneticist Louis-Marie Houdebine. She used the green fluorescent protein found in jellyfish, which fluoresces green in exposure of blue light, to create Alba, a glow in the dark fluorescent bunny. Kac describes Alba to The Boston Globe as an animal, which does not exist in nature, having a “particularly mellow and sweet deposition”.[17] This article generated a global media scandal. Another project highlighting societal loose ends asks people whether they know where all their DNA is. Heather Dewey-Hagborg printed 3D-portraits from strangers whose DNA she found on stray hairs and chewing gum.[18]

It is fair to remain sceptical about the role of the artist in the scientific field. By using the techniques, workspaces and methods of scientists, artists have similar boundaries and can, therefore, be influenced by the field they should be reflecting on. Ziakerek describes this phenomenon as the complicity trap.[19] If art is complicit with technological developments instead of contesting them, it may help their popular acceptance. This art is often more repetition than rupture, which makes people question the value of the artists’ contribution. Humanity should carefully preserve artistic integrity and independence from the sciences by providing a separate workspace for them.

Initiatives have been launched to inform people about recent advances in human gene-editing research. One example is the Working Party raised by the Nuffield Foundation council on Bioethics, aimed at discussing ethics surrounding genome editing and human reproduction. Involved are ethical lawyers, bioethicists, medical professionals, partners and sociologists.[20]

The speed at which these technologies are developing has unnerved many policymakers and stakeholders about whether appropriate systems are in place to govern these technologies. The National Academies of Sciences, Engineering and Medicine has taken leadership in the past on controversial new areas of genetic research, such as cloning and gain-of-function research. They ask how and when the public should be engaged in the decision making. An expert committee considers important questions, including balancing potential benefits with unintended risks, governing use of genome editing, incorporating societal values into clinical applications and policy decisions, and respecting inevitable differences across nations and cultures, which will shape how and whether to use these new technologies. They propose criteria for heritable germline editing and provide conclusions on the crucial need for public education and engagement. In addition, they present seven general principles for governance of human genome editing.[21]

The prospect of human freedom unchained is appealing to all. Yet its promise is flawed. The consequences cannot be overseen, and some argue humanity is at stake. Public surveys have shown people worry about the impact this new biotechnology might have on their life. They fear for their wellbeing, authenticity and identity. However, banning technological research is not an option. Luckily, participation grants insight in further technological research. Public engagement and education is of great importance, so the general public can contribute to the debate surrounding human enhancement. BioArt can serve as a catalyst for involvement. More awareness should be raised on the topic of human enhancement, so political regulation and legal barriers can be implemented. Constraining these new technologies out of respect for nature and with a heedful eye at humanity’s future is a necessity.

 

[1] Kuzgesagt, Genetic Engineering Will Change Everything Forever – CRISPR, 10 Aug 2016

[2] M. J. Sandel, The Case Against Perfection, The Atlantic. 2004 April

[3] Le Cong, F. Ann Rann, David Cox, Shuailiang Lin, Roberto Barretto, Naomi Habib, Patrick D. Hsu, Xuebing Wu, Wenyan Jiang, Luciano A. Marraffini and Feng Zhang, Multiplex Genome Engineering Using CRISPR/Cas Systems, Science. 2013 Feb 15; 339(6121): 819-823
Link to article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795411/

[4] Eun Ji Kim, Ki Ho Kang and Ji Hyeon Ju, CRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells, Korean J. Intern Med. 2017 Jan; 32(1): 42-61
Link to article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214730/

[5] Liang P1, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, Lv J, Xie X, Chen Y, Li Y, Sun Y, Bai Y, Songyang Z, Ma W, Zhou C, Huang J. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell. 2015 May;6(5):363-72.
Link to article: https://www.ncbi.nlm.nih.gov/pubmed/25894090

[6] Dieter Egli, Michael Zuccaro, Michal Kosicki, George Church, Allan Bradley, Maria Jasin. Inter-homologue repair in fertilized human eggs? August 28, 2017
Link to article: http://www.biorxiv.org/content/early/2017/08/28/181255

[7] Mirjam Schuijff en Geert Munnichs. Goed, beter, betwist – Publieksonderzoek naar mensverbetering. Rathenau Instituut
Link to article: https://www.rathenau.nl/nl/publicatie/goed-beter-betwist-publieksonderzoek-naar-mensverbetering

[8] A. Gee, A world without Down Syndrome. BBC News Magazine. 2016 September 29
Link to article: http://www.bbc.com/news/magazine-37500189

[9] N. Bostrom, Human Genetic Enhancements: A Transhumanist Perspective. The Journal of Value Inquiry 37: 493–506, 2003. © 2004 Kluwer Academic Publishers.

[10] P. Z. Myers, Singularitarianism, 2011 February 13

[11] F. Fukuyama, Our Posthuman Future: Consequences of the Biotechnology Revolution. 2002

[12] Philippe Lepers “Baudrillard: Leven na de orgie”. Klement. 2009

[13] Friedrich Nietzsche, Jenseits von Gut und Böse, 1886

[14] E. Callaway, Deal done over HeLa cell line, Nature. 2013 August 07
Link to article: http://www.nature.com/news/deal-done-over-hela-cell-line-1.13511

[15] D. McLellan, John Moore: Sued to Share Profits From His Cells, LA Times. 2001 October 13
Link to article: http://articles.latimes.com/2001/oct/13/local/me-56770

[16] R. Zwijnenberg, A two headed zebrafish, University leiden. 2012

[17] Gareth Cook, Cross hare: hop and glow, Globe Newspaper Company. 2000 September 17
Link to article: http://www.ekac.org/bostong.html

[18] T. Ghose, Bio-Art: 3D-Printed Faces Reconstructed from Stray DNA, Life Science. 2015 March 16
Link to article: https://www.livescience.com/50146-art-genetic-data-privacy.html

[19] Krzysztof Ziarek, The Force of Art. Stanford University Press. 2004

[20] Nuffield Council on Bioethics, Site by Public Life
Link to website: http://nuffieldbioethics.org/project/genome-editing/working-party

[21] National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press.
Link to article: https://doi.org/10.17226/24623