Abstract

Due to its low cost and easy handling, nanopore sequencing has great potential to become a consumer product. The widespread use of DNA sequencers would, however, create new social, legal, and ethical challenges.

Nanopores

Nanopores, irrespective of whether they are man‐made or naturally occurring, are defined as holes with a diameter between 1 and 100 nm and are used in a variety of applications from DNA and protein sequencing (Johnsonet al, ²⁰¹⁷; Huet al, ²⁰²⁰) to filtering (Liet al, ²⁰¹⁶) and nanomedicine (Majdet al, ²⁰¹⁰). The versatility and scalability of nanopore technology have raised significant interest in research as demonstrated by the increasing number of publications on the topic (Fig 1) and in industry with a number of companies focusing on various aspects of nanopore technology, including fabrication, measurement, or DNA and protein sequencing. The latter in particular has become popular in the life sciences as one of the Next Generation Sequencing (NGS) methods with applications in genomic mapping, population genomics, and evaluating genetic risk factors for diseases. Recently, it has also been used to detect SARS‐CoV‐2 variants (Smith, 2021). In contrast to other sequencing technologies, nanopore‐based sequencing is cheaper, very easy‐to‐use, does not require much computational and lab infrastructure, and only needs a small amount of DNA in a test sample.

… nanopore‐based sequencing is cheaper, very easy‐to‐use, does not require much computational and lab infrastructure, and only needs a small amount of DNA…

It is, in fact, these characteristics that would make nanopore sequencers an ideal consumer product. Oxford Nanopore, which pioneered the technology, has already developed small handheld devices (Fig 2) that can be used in the field or the clinic for direct sequencing. As Gordon Sanghera, the CEO of Oxford Nanopore Technologies, commented, the popularity of the nanopore technology will contribute to a “large and terrific shift” in the usage of genetic information similar to the computer revolution during the past decade (Riding Unicorns, 2022).

There are clearly opportunities but also risks when consumers outside a professional research environment get access to powerful DNA sequencing technology. As nanopore‐based sequencing as a consumer technology has both positive and negative implications, a discussion through the lens of social science will help to map the challenges and unintentional negative consequences it may create for society in the same way the social sciences have contributed to analyzing the potential impact of nanotechnology and synthetic biology (Shapiraet al, ²⁰¹⁵). These in turn would inform politicians and lawmakers when it comes to regulating the use of consumer sequencing technology. Studies and suggestions from the humanities and social sciences will also help to guide responsible research and direct the trajectory of growth of this technology.

DNA sequencing technology for consumers

The high portability and affordability of nanopore sequencers could lead to pervasive DNA sequencing. Along with many bona fide applications—for instance, testing for the presence of pathogens or food contaminants—it could also encourage illegal or at least harmful uses such as unauthorized ancestry tracking, self‐testing for genetic risk factors, or parental tests without the consent of those whose DNA is being sequenced.

The high portability and affordability of nanopore sequencers could lead to pervasive DNA sequencing.

In many cases, the discussion of the ethical, legal, or societal implications (ELSI) only took place after a new technology was nearly or fully developed and reached the market, which left little room for change, policies, or regulation at this late stage. This was the main reason why, in the late 1990s, the funders of the Human Genome Project decided to involve the humanities and social sciences in the research stage and established an active ELSI program. These scholars explored and mapped the positive and negative societal impacts of DNA and full‐genome sequencing and made recommendations to funders and policymakers (Hanna, 1995). Most of the ethical, legal, and societal issues related to DNA sequencing per se have been widely discussed and addressed in the form of regulations and laws.

The advent of consumer DNA sequencing technology raises many of the same ELSI that were discussed more than 20 years ago in the context of the Human Genome Project and subsequently about full‐genome sequencing (McGuireet al, ²⁰⁰⁸). However, it also creates novel concerns since the laws and regulations that have been put in place may not be sufficient to prevent potential abuse of nanopore sequencing once it becomes a widely accessible consumer technology. These concerns—loss of privacy, sharing of genetic information, confidentiality of personal data or consent by the elderly, children, or other dependants, and so on—are not novel per se, but nanopore sequencing would move them out of the realm of research and clinics into wider society.

Nanopore‐based sequencing technology

Nanopore sequencing technology is based on measuring current fluctuations along the pore, which sits between two reservoirs of the same electrolyte. A voltage applied over the pore causes a small current to flow. When a molecule, say DNA, translocates through the pore, the ionic current changes; the analysis of these fluctuations reveals which nucleotide passed through the pore. As nanopore sequencers move a single DNA molecule through the pore, they can determine the DNA sequence directly based on the current fluctuations without the need for presequencing PCR amplification and postsequencing computation to assemble the sequence from a microarray read.

There are mainly three types of nanopores used for sequencing: biological, solid‐state, and hybrid nanopores. The biological variety is usually pores such as MspA or α‐hemolysin in a lipid bilayer membrane while solid‐state nanopores are fabricated from artificial membranes such as silicon nitride by dielectric breakdown, laser‐assisted milling, ion beam milling, or transmission electron microscopy. So far, only biological nanopores have been used for nanopore DNA sequencing. There is much interest and research in solid‐state nanopores as these are potentially superior to their biological counterparts owing to their chemical and mechanical stability, scalability, and integration capacity with electronic devices. DNA sequencing using solid‐state nanopores still faces limitations though, such as controlling the speed of molecule translocation.

The increase in the number of patents in any particular field is an indicator of the increasing industrial interest and potential commercial value. A search onlens.org, a free patent search engine, yielded 38,758 records for the term “nanopore” and 21,731 records for the term nanopore sequencing in early 2023. Moreover, the number of patents related to nanopore sequencing has been increasing exponentially during the past 20 years (Fig 3).

Nanopore sequencing is not limited to DNA though: Academic and industry are further developing the technology to expand it to protein sequencing for use in research and diagnostics. Generally, the potential ability to detect single molecules from a sample holds great potential for applications in research, clinical diagnostics, food safety, environmental monitoring, biosafety and biosecurity, and so on.

The biological nanopore DNA sequencing technology was first commercialized in 2005 by Oxford Nanopore Technologies (ONT), a spinout from Oxford University in the UK. Backed up with more than 2,000 relevant patents (https://nanoporetech.com/about‐us/intellectual‐property), the company has become a major player in DNA sequencing technology. New startups are now developing instruments based on solid‐state nanopores, such as Northern Nanopore Instruments, Quantapore or Ontera. Other companies supply essential parts such as current amplifiers or flow cells; according tonanoporesite.com, 27 companies are involved in this area. The global nanopore technologies market is projected to reach more than US$ 600 million by 2030 (https://www.alliedmarketresearch.com/nanopore‐technologies‐market‐A11864.). Nonetheless, nanopore sequencing is still a smaller player in the global DNA sequencing market, which is anticipated to reach a value of US$ 29 billion by 2028 (Research and Markets, 2022).

The ethical issues of nanopore sequencing

Since the human genome project with a price tag of US$2.7 billion in 2000, sequencing has become cheaper and faster—a full‐genome sequence nowadays costs less than US$ 1,000 and takes less than a day using massive parallel microarray NGS. Nanopore sequencing makes it much more affordable and easy‐to‐use in the field with small handheld devices—Oxford Nanopore's portable MinION Mk1C costs less than US$ 5,000 compared with Illumina's NovaSeq Series sequencers, which start at more than US$ 800,000. This enables new applications without the need for sending samples to a laboratory, such as direct sequencing in the field of ecology or population genetics research, rapid diagnostics in the clinic, or surveillance of the presence and distribution of pathogens.

It also could turn portable nanopore sequencers into a consumer product rather than a research or diagnostic tool. Consumer DNA sequencing would give anyone access to a technology that so far has been limited to research, clinical diagnostics, law enforcement, and private companies. This has enormous potential for applications: Consumers could test themselves for pathogens, for bacterial contaminants in food, or monitor their homes for pathogenic bacteria or viruses. Interested citizen science laypeople could greatly contribute to ecology or population genetics research projects by sequencing samples in the field. Biology education in schools would also greatly benefit from affordable and easy‐to‐use DNA sequencers. But it would also enable parents to test whether their children have an inherited genetic disorder or to conduct a paternity test. It would enable anyone to test him or herself or anyone else for genetic risk factors for diseases or determine their ethnic background. It could allow any user to test whether a particular individual has been at a certain location, say the bedroom or bathroom.

These possibilities raise serious concerns about privacy, discrimination, informed consent, the ‘right to know’ versus the ‘right not to know’ in case of severe inherited diseases, sequencing the DNA of children or the elderly who are not able to give informed consent or what to do with an unexpected diagnosis without adequate counseling. Given that nanopore sequencers are not 100% accurate and require several reads and careful analysis to generate reliable sequence data, this may lead to false assessments. Moreover, the reuse of sequence data generated this way by third parties, their storage, and sharing raises additional ethical concerns (Cambon‐Thomsen, 2004; Doveet al, ²⁰¹⁴; Sherkowet al, ²⁰²²; Wanet al, ²⁰²²).

None of these issues are new and have been intensely discussed during and since the Human Genome Project. These have also been addressed in laws and regulations that govern the generation and use of DNA sequence data by research institutions, clinics, law enforcement, and private companies. However, as these mostly apply to institutional actors, it is not clear whether the existing regulatory and legal framework would be sufficient to prevent abuse and misuse by individual actors.

Consumer DNA sequencing would give anyone access to a technology that so far has been limited to research, clinical diagnostics, law enforcement, and private companies.

Political and legal issues

Nanopore technology gives the ability to sequence anything, anywhere, anytime. Hand‐held nanopore sequencers have been successfully tested under harsh conditions such as Antartica². The technology's portability and affordability can equip underrepresented communities with affordable sequencing capabilities for onsite diagnostics or pharmacogenetics, which would greatly strengthen developing countries' capacity to fight infectious diseases. For example, British and Brazilian researchers deployed nanopore sequencers in Brazil to analyze clinical samples for the presence of the zika virus (Quicket al, ²⁰¹⁷). This easy and rapid onsite diagnosis will contribute to the early detection of diseases or help to track mutations of important pathogens such as SARS‐CoV‐2. It will allow governments and healthcare experts to quickly develop preventive measures to stop the spread of diseases and reduce causalities. This technology can also contribute to education giving teachers the means to practical‐oriented teaching of genetics and biology.

If nanopore‐based sequencing becomes ubiquitous, this may lead to political problems or even national security matters. Portable sequencers can be easily abused by the state for identifying people from underrepresented communities, refugees, or ethnic minorities who would be the target of discrimination or oppression. Even though this is already possible with other sequencing technologies, portable and low‐cost nanopore‐based sequencers would make it much more easy.

Portable sequencers can be easily abused by the state for identifying people from underrepresented communities, refugees, or ethnic minorities who would be the target of discrimination or oppression.

Related to this, nanopore sequencers could challenge existing laws that ensure privacy and the safety of genetic information. In the USA, the 2008 Genetic Information Nondiscriminatory Act (GINA) specifically prohibits health insurances and employers from discriminating people using genetic data. The 1996 Health Insurance Portability and Accountability Act further prohibits any healthcare providers and business from sharing such information without the consent of the person. In Europe, the General Data Protection Regulation (GDPR) protects individuals' personal data, including genetic information. There are similar laws in other countries such as the Personal Information Protection and Electronic Documents Act (PIPEDA) in Canada, the Privacy Act in Australia, and the DNA Technology Regulation Bill, which is under consideration in India. There are also specific laws that regulate the storing, sharing, and analyzing the genetic information of criminals in Ireland, the UK or South Africa.

An easy‐to‐use sequencing technology could challenge this legal framework. For example, a child could secretly conduct a paternity test or a father could test his child whether he is really the biological father. Before the advent of nanopore sequencing, paternity tests were usually done by specialized laboratories only after authorization by a court. Similarly, someone could use a customer DNA sequencer to track an individual and test for the presence of this person in certain locations or secretly test for genetic risk factors related to diseases or behavior. Hence there is a need for extending existing laws and regulations that protect the genetic information of individuals to prevent unauthorized usage of genetic data by individual users.

… the existing laws and regulations that were mostly created to cover businesses and institutions may no longer be effective to prevent abuse and misuse by individuals.

Again, these concerns are not new, but as nanopore sequencing greatly expands the potential users and customers of DNA sequencing, the existing laws and regulations that were mostly created to cover businesses and institutions may no longer be effective to prevent abuse and misuse by individuals. As the science and the applications are complex and constantly evolving, it will be challenging to draft the laws and regulations that cover these and potential future applications of DNA sequencing by people. Hence, there is a need for intense discussions that involve natural and social scientists, ethicists, legal experts, and politicians.

Conclusion

The rapid growth and diverse applications of nanopore DNA sequencing technology have made it a valuable tool for scientific research. The development of portable sequencing devices is a paradigm shift in sequencing technologies. However, the easy accessibility and potential of a consumer sequencer raise serious concerns about the ethical, social, legal, political, and security implications of this technology. Specific policies and regulations that are fair, responsible, and respectful of the values and rights of individuals need to be put in place to regulate the use of this technology and mitigate any negative impacts on society.

Despite many scientific publications on nanopore technology, there have not been many efforts to explore the social science and ethical implications of nanopore sequencing technology and its implications. As this technology penetrates more into the market for individual consumers, we may have to involve research centres such as the Centre for Nanotechnology in Society or the Science Justice research centre to start and organize a debate on how to safely employ this technology while ensuring its benefits for society. This is not novel terrain: The human genome project, synthetic biology, or nanotechnology have been accompanied and their public acceptance strengthened by involving social scientists, ethicists, and lawyers during the research and development of these technologies.

I hope this article will generate interest among experts in social science, policy, and law to explore these aspects of nanopore technology and generate productive discussions. This will provide opportunities such as sharing knowledge across the natural and social sciences, help to project unintentional negative consequences of nanopore sequencing technology, and help to shape the growth and trajectory of nanopore technology with ethical and humanitarian values.

Author contributions

Muhammad Sajeer P: Conceptualization; formal analysis; investigation; visualization; methodology; writing – original draft; writing – review and editing.

Disclosure and competing interests statement

The author declares that he has no conflict of interest.

Supporting information

Acknowledgements

I acknowledge the help and support from my PhD supervisor Prof, Manoj Varma from CeNSE, IISc Bangalore. Thanks to Prathyay Sarkar, IISc Bangalore for the fruitful discussions. I also acknowledge the other nanopore group (https://sites.google.com/view/nanoporegroup/home) members namely Anumol Dominic, Mayank Mitram, Muddu Krishna, Anu Roshini, Jaise Johnson, Pranjal Sur, Shree sumanas, Divya Mohan and Avisekh Pal for providing their critical suggestions during discussions. I also thank the PhD fellowship from the Government of India.

EMBO reports (2023) 24: e56619

References