Introduction
Regulation, by necessity, introduces rigidity to otherwise flexible processes. Done proportionately, this can be an efficient societal device for preventing harm. At the same time, inherent regulatory rigidity creates particular challenges when the nature of the regulatory target changes quickly or unexpectedly.
Disruptive technologies in life sciences - a very dynamic field of activity are a good example of this. Disruptive technologies challenge the way a sector operates, and it is self-evident that (in most cases) this will also have an impact on the relevant normative framework. This effect is most visible in areas which have a direct impact on human life and wellbeing, as these areas are tightly (and often, rather specifically) regulated, and a failure to control a technology appropriately may lead to undesirable outcomes.
The dual purposes of preventing harm through proportionate regulation and maintaining trust in innovation mean that it is all the more important to ensure that regulation is adequately responsive and flexible to react to a disruptive technology. This can be a difficult line to tread, particularly in fields where research and development is also morally or ethically contentious.
We will illustrate the context and challenge of regulating disruptive technologies by discussing two specific case studies: artificial intelligence, and cell and gene therapy. In both cases, we suggest that the current regulatory framework in the UK strikes an appropriate balance between precaution and freedom of research, allowing for innovation subject to strict controls and licensing frameworks. There are, however, numerous challenges which need to be considered and addressed as these technologies advance. Regulators, policy makers and innovators working in this sector must continue to work together to ensure that responsible science is allowed to flourish.
Artificial intelligence
The science of making machines do things that would require intelligence if done by people (Definition of artificial intelligence from the Proposal for the Dartmouth Summer Research Project on Artificial Intelligence, 1955.)
Artificial intelligence (AI) technologies hold the potential to significantly improve health and care, providing faster and more accurate diagnosis, speedier treatments, and facilitating medical breakthroughs through drug discovery.
This is particularly the case in contexts where the pattern-recognition strengths of AI can be deployed to their fullest potential. Tasks such as the correct identification of tumour cells, recognition of areas of concern in medical imaging, and the processing of large amounts of genomic data can be carried out with much greater speed and accuracy by algorithms that learn from previous datasets, and develop their own datasets from which to learn from in the future. The ability to check a patients image or test result against all other available and comparable datasets is, at first glance, far superior to a clinicians ability to make an assessment on the basis of his or her experience.
At the same time, this does give rise to risk. For example, there is an inherent (and proven) risk that an algorithm which learns on the basis of historic human-generated data also takes on the biases that human decision-making has inevitably introduced. So how does regulation play a part in addressing this risk?
The first point to make is that no one body is solely responsible for regulating the adoption of AI technologies in the UK healthcare sector. A number of different regulatory bodies have a remit to oversee aspects of AI, including the Medicines and Healthcare products Regulatory Agency (MHRA) and the Information Commissioners Office (ICO). In addition, there are nonregulatory bodies which also play an important role, including the National Institute for Health and Care Excellence (NICE) and NHSX. However, no one institution has overall responsibility for policing, for example, the prevention of bias in AI algorithms. The most effective way of addressing this risk at present is to avoid exclusively automated decision-making so that the use of AI technologies in the clinical setting will focus instead on assisted decision-making and triage. The application of this approach will come down to individual healthcare payors and providers: in the absence of any direct regulation, it is left to them to decide how best to mitigate risk, and whether and if so how to apply nonbinding codes of conduct, such as the Department of Health and Social Cares code of conduct for data-driven technologies which seek to address the risk.
Reliance on nonbinding codes of conduct as a substitute for regulation may not be ideal and can result in a lack of certainty. Equally, overlapping codes, rules and regulations also pose a risk, for example, as to how NICEs evidence standards framework for digital health technologies interacts with MHRA regulations concerning software as a medical device in relation to clinical evidence. The risk is lack of clarity; the mitigation is raising awareness.
Another challenge arises where regulation designed for a specific purpose is used for a new purpose, for example the application of MHRA regulations designed for traditional medical devices to software incorporating algorithms. A recent state of the nation survey on the use of AI in health and care revealed that half of all software developers were not intending to seek CE mark classification, with the most commonly cited reason being that they did not believe the medical device classification was applicable. It is essential that the sector raises awareness of these requirements, albeit that they are complex and sometimes impenetrable.
One significant area of concern is how existing laws relating to negligence, liability and insurance apply to the clinical use of AI whether in assisting decision-making about a patients treatment, or in the operation of medical devices. Currently, claims are almost always brought against the treating clinician or healthcare provider, but for a clinician using big data analysis as well as his or her own experience, where does the division of responsibility lie? If a patient is injured as a result of a malfunction in an AI-driven device, does liability lie with the manufacturer of the device, the programmer who wrote the code which operates the device, the clinical team, the hospital or all of the above? It remains to be seen whether this will give rise to novel constellations of liability, such as an increase in manufacturers liability or a change in statutory and wider insurance requirements.
One of the major areas of opportunity for AI-based technologies is biomedical research where the strengths of speed and range have huge potential. The extrapolation of the potential of certain compounds against huge databases of similar compounds is commercially powerful. The ability to quickly check clinical trial design against public registries of published results to avoid unnecessary duplication of human-based experimentation is ethically desirable. But as innovators seek to improve drug discovery using AI, it will be important to continue to keep under review laws relating to intellectual property and how they apply to AI-based technologies.
Cell and gene therapy
The area of cell and gene therapy is of particular significance, and great potential, in regenerative medicine. It has seen a decade-long genesis since its inception, and it does not immediately strike one as a field that meets the definition of a disruptive technology. At the same time, however, it provides a good illustration of how a technology may mature for a long time, or be repurposed in an unexpected way, before it becomes disruptive.
The field has come a long way since the first systematic trials in 1989, and by now, there are 17 FDA-approved cell and gene therapy products. Over and beyond technical questions of the safety of the vectors used for the manipulation of cells, there are few remaining ethical and legal issues in relation to somatic cell gene therapy for particularly debilitating conditions (i.e. where the manipulation does not lead to heritable genetic characteristics).
From a regulatory and ethical perspective, however, cell and gene therapy becomes more complex where germline gene therapy is used. The modification of the human germline is subject to significant debate and, in some jurisdictions, strongly prohibitive regulation. The advent of disruptive technologies such as CRISPR/Cas9 prime editing techniques, with their associated precision and purported safety, have already reignited the debate around the prohibition of germline manipulation, with some commentators calling for a relaxation of the regulation while others demand either a global ban or at least a moratorium.
Although the United Kingdom has a reputation of being a liberal jurisdiction for research, it is in fact very tightly regulated and only potentially permissive. UK law reects a compromise: we permit research (including research involving germline gene editing), but we subject such research to strict scrutiny, licensing and oversight, and we criminalise unlicensed research. That being said, the legislation is drafted in such a way as to facilitate a broad variety of research, including (again, potentially) the introduction of novel techniques, and few procedures are prohibited. Overall, this framework helps allay public and political concern about what is often controversial research and provides a degree of protection for researchers operating under a licence, facilitating innovation. Such a robust framework is particularly valuable when it comes to considering how best to address the clinical application of germline genome modication. In circumstances where UK law is comprehensive and clear in its application to gene editing, there is no merit or purpose in a moratorium or further restriction on the use of this technology as some have demanded.
Concluding remarks
The UK has a mature and robust regulatory framework governing research and development in life sciences. We have a successful history in regulating numerous disruptive and controversial new technologies, such as stem cell research, the creation of human-animal hybrids, the clinical use of preimplantation genetics, and mitochondrial donation all testaments to the strength of this framework and its capacity to adapt to accommodate new technologies. This success, however, has been built upon a vital foundation of open and accessible dialogue between innovators, parliamentarians, policy makers and the public, and it is to be hoped that a similar transparency will be maintained in the future. Such dialogue will also ensure that if there are gaps or restrictions in regulation that need to be addressed to avoid stifling innovation, these can be pre-empted.
More:
A short guide to regulation for disruptive technologies - Lexology
- Politics of Stem Cell Research - May 7th, 2011 [May 7th, 2011]
- Obama Ends Funding Ban for Stem Cell Research - May 8th, 2011 [May 8th, 2011]
- Stem Cell Research: A Father's Fight - May 10th, 2011 [May 10th, 2011]
- Human Embryonic stem cell research - May 11th, 2011 [May 11th, 2011]
- Frost Over The World - Stem Cell Research and Turkey -26 Oct - May 20th, 2011 [May 20th, 2011]
- McCain Favors Embryonic Stem Cell Research - May 20th, 2011 [May 20th, 2011]
- US divided over stem cell research reversal - 09 Mar 09 - May 21st, 2011 [May 21st, 2011]
- The Politics and Promise of Stem Cell Research - May 22nd, 2011 [May 22nd, 2011]
- Inside Story - Obama to end stem cell research ban - March 9 - Part1 - May 30th, 2011 [May 30th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Douglas Boyd - June 3rd, 2011 [June 3rd, 2011]
- The Human Embryo and Embryonic Stem Cell Biology: Spotlight on Stem Cell Research - June 3rd, 2011 [June 3rd, 2011]
- US appeals court lifts stem cell research ban - June 7th, 2011 [June 7th, 2011]
- Trailer for Mapping Stem Cell Research: Terra Incognita - June 9th, 2011 [June 9th, 2011]
- Politics: President Obama on Stem Cell Research - June 10th, 2011 [June 10th, 2011]
- Stem Cell Research Documentary - June 11th, 2011 [June 11th, 2011]
- TEDxSingapore - Susan Lim - Hype and hope of stem cell research - June 13th, 2011 [June 13th, 2011]
- Lou Gehrig's Disease (ALS): Spotlight on Stem Cell Research - Wrapup - June 14th, 2011 [June 14th, 2011]
- The Next Frontier in Stem Cell Research - June 17th, 2011 [June 17th, 2011]
- Robert Klein: Stem Cell Research - June 22nd, 2011 [June 22nd, 2011]
- Fibrocell Stem-Cell Wrinkle Smoother Wins FDA Clearance - June 23rd, 2011 [June 23rd, 2011]
- The Politics of Stem Cell Research - June 23rd, 2011 [June 23rd, 2011]
- A Dose of Reality on Alternative Stem Cell Treatments: What you don't know can hurt you - June 28th, 2011 [June 28th, 2011]
- Governor Tim Pawlenty Discusses Stem Cell Research - June 30th, 2011 [June 30th, 2011]
- The EU and stem cell research - July 5th, 2011 [July 5th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Jeff Bronstein - July 6th, 2011 [July 6th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Yung-Wei Chi - July 7th, 2011 [July 7th, 2011]
- Spotlight on Cancer Stem Cell Research - July 11th, 2011 [July 11th, 2011]
- A Stem Cell Story - July 12th, 2011 [July 12th, 2011]
- Bishop Blair bars support for Komen breast cancer group - July 13th, 2011 [July 13th, 2011]
- Stem Cell Research In Toronto - July 14th, 2011 [July 14th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Introduction - July 14th, 2011 [July 14th, 2011]
- Huntington's Disease: Spotlight on Stem Cell Research 2007 - Han Keirstead - July 15th, 2011 [July 15th, 2011]
- TMconfUK2011-08 - Stem Cell Research in the UK - Prof Charles Ffrench-Constant - July 16th, 2011 [July 16th, 2011]
- UCSF opens stem cell research building - July 16th, 2011 [July 16th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - John Zaia - July 17th, 2011 [July 17th, 2011]
- Deafness: Spotlight on Stem Cell Research - Ebenezer Yamoah - July 22nd, 2011 [July 22nd, 2011]
- Spotlight on Basic Stem Cell Research - Irv Weissman - July 25th, 2011 [July 25th, 2011]
- Diabetes: Spotlight on Stem Cell Research - Peter Butler - July 27th, 2011 [July 27th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Arnold Kriegstein - July 27th, 2011 [July 27th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - Loren Leeds - July 27th, 2011 [July 27th, 2011]
- Alzheimer's Disease: Spotlight on Stem Cell Research - Leeza Gibbons - August 2nd, 2011 [August 2nd, 2011]
- Geron's Embryonic Stem Cell Clinical Trial for Spinal Cord Injury - August 3rd, 2011 [August 3rd, 2011]
- The Skin Gun stem cell research - August 10th, 2011 [August 10th, 2011]
- Deafness: Spotlight on Stem Cell Research - Karen Doyle - August 10th, 2011 [August 10th, 2011]
- Stem Cell Research: Huntington's Disease - August 14th, 2011 [August 14th, 2011]
- Adult and Non-Embryonic Stem Cell Research Conference at Notre Dame - August 20th, 2011 [August 20th, 2011]
- Stemcell Research and Aging - Panel 1 - August 22nd, 2011 [August 22nd, 2011]
- Texans for Stem Cell Research Learn for Life: KXAN Coverage Aired August 16th, 2011 - August 24th, 2011 [August 24th, 2011]
- Stem Cell Research: Macular Degeneration - September 18th, 2011 [September 18th, 2011]
- Brilliant Minds - Stem Cell Research | Tomorrow Today - September 25th, 2011 [September 25th, 2011]
- Ethics of Stem Cell Research (1) - September 29th, 2011 [September 29th, 2011]
- Legal and Public Policy Dimensions of Stem Cell Research - September 29th, 2011 [September 29th, 2011]
- Stem cell symposium - October 2nd, 2011 [October 2nd, 2011]
- StemCONN 2011, The Latest in Stem Cell Research - October 6th, 2011 [October 6th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Mark Genovese - October 7th, 2011 [October 7th, 2011]
- Judy Roberson: Patient advocates drive stem cell scientists - October 8th, 2011 [October 8th, 2011]
- Sam Harris - Stem Cells and Morality - October 8th, 2011 [October 8th, 2011]
- Stem Cell Research, Ethics and Religion - October 9th, 2011 [October 9th, 2011]
- Stem Cells: Fulfilling the Promise - 2011 CIRM Grantee Meeting - October 10th, 2011 [October 10th, 2011]
- The Skin Gun (Stem Cell research to replace burnt off skin. Done in 3 days!) - October 13th, 2011 [October 13th, 2011]
- Alzheimer's Stem Cell Research Patient Advocate Spotlight: The Faces of Neurodegenerative Disease - Video - October 18th, 2011 [October 18th, 2011]
- Life in the Balance: Perspectives on Stem Cell Research - Video - October 18th, 2011 [October 18th, 2011]
- Stem Cell Research Funding Halt - Video - October 19th, 2011 [October 19th, 2011]
- Vatican lending hand in adult stem cell research - Video - October 20th, 2011 [October 20th, 2011]
- First Spinal-Cord Surgery With Stem Cells - Video - October 21st, 2011 [October 21st, 2011]
- Michael J. Fox Embryonic Stem Cell Research - Video - October 22nd, 2011 [October 22nd, 2011]
- stem cell research - Video - October 22nd, 2011 [October 22nd, 2011]
- Gayle Atteberry - Cloning - November 5th, 2011 [November 5th, 2011]
- It Takes Nerve: UC Irvine - Sue - November 6th, 2011 [November 6th, 2011]
- Embryonic Stem Cell Research - Video - November 9th, 2011 [November 9th, 2011]
- Adult Stem Cell Research Far Ahead of Embryonic - Video - November 10th, 2011 [November 10th, 2011]
- Is stem cell research a growing concern .flv - Video - November 10th, 2011 [November 10th, 2011]
- Forbes Discusses Stem Cell Research - Video - November 14th, 2011 [November 14th, 2011]
- Stem Cell Research Presentation - Video - November 16th, 2011 [November 16th, 2011]
- Benedict XVI: No embryonic stem cell research - Video - November 28th, 2011 [November 28th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - A Father's Story - Video - November 30th, 2011 [November 30th, 2011]
- CIS 111 Digital Media Project - Stem Cell Research - Video - December 13th, 2011 [December 13th, 2011]
- Regenerative Medicine and Applications of Stem Cell Research - Video - December 20th, 2011 [December 20th, 2011]
- Stem Cell Research Today: Larry Goldstein - CIRM Science Writer's Seminar - Video - December 22nd, 2011 [December 22nd, 2011]
- CIRM Bridges Award: Building California's Stem Cell Research Workforce - Video - December 22nd, 2011 [December 22nd, 2011]