A Genomics England & Centre for Personalised Medicine Collaboration: Ethical, Legal and Social Issues in Diversifying Data

Despite the huge advances in technologies that have enabled cheaper, more routine and widespread use of genomics in healthcare, the datasets that underpin the majority of genomic insights, remain built on those  dominated by individuals from Western countries, of European ancestry. The research and clinical impacts of this vary and include: misclassification of variant pathogenicity, more Variants of Unknown Significance (VUSs) in non-Europeans or potential inequalities driven by polygenic score-informed screening, developed on non-representative populations. The need to diversify genomic data and improve the evidence-base for genomics-enabled personalised medicine goes beyond merely collecting more data, but draws in a range of ethical, legal and social issues including but not limited to: consent, societal implications, implications regarding health inequity and personal responsibility, language and concepts, potential beneficiaries, public-private partnerships and data governance. 

This context underpins the rationale behind the creation of Diverse Data,  a new initiative led by Genomics England that aims to reduce inequalities in genomic medicine, and improve genomic outcomes for underserved communities. It also drives home the centrality of embedding ethics into all aspects of initiatives that aim to improve equity and diversity in genomics, to ensure that any efforts are as robust as possible in their aims, governance, design, and delivery. 

There are of course, huge benefits of setting up initiatives from scratch; you benefit from advances in technology in a space where a few years makes all the difference, you can make new and fresh collaborations and connections as “the new kid on the block”, and you can stand on the shoulders of global efforts by learning from the insights and hard work of others from previous years and decades. “The road to hell is paved with good intentions”, or more more recently said and specifically related to genomics, Adam Rutherford in his latest book Control: The Dark History and Troubling Present of Eugenics wrote:  “We must always expect science to be misrepresented, overstated and misunderstood, because it is complex, because the data is unending, and because people are strange”. Whilst the ambitions of the Diverse Data initiative are well-intentioned, there are many many ways in which such a programme could not do good, or even worse, cause harm. 

Some examples of important ethical questions that were raised early for us include:

• The true or the perceived risk of creating a link between race and genomics, including the potential for this work to be misconstrued as giving scientific backing to such a link. 
• The risk of misunderstanding health inequalities by focusing on genomic diversity in the absence of wider socio-economic factors such as deprivation
• The potential negative impacts of new, additional burden from personalised medicine, in the face of poor health outcomes better addressed through other means, largely affecting social determinants of health. 
• The potential unforeseen or unintended consequence of using a consent model that is not adapted or designed to be culturally tailored for participants

In order to have the broadest and most systematic understanding of potential risks, the Diverse Data initiative commissioned a review into the potential unintended consequences of efforts to diversify genomic data, and we were thrilled that Clinical Ethics, Law and Society at the University of Southampton (CELS) and the Centre for Personalised Medicine at the University of Oxford (CPM), from a hugely rich and high-quality number of submissions, undertook the project. 

The CELS/CPM team worked at full speed, reviewing the literature, running workshops, conducting interviews and supporting a deliberative conversation between researchers and participants.

Here are the key takeaways:

1. Research practices are often  exclusionary

Many research practices are exclusionary and need to change.  Examples include approaches to recruitment or data collection that do not consider the cultural setting in which potential participants are situated. Research also often lacks reflexivity about diversity on the part of researchers and research institutions.

2. Co-design is key

Co-design is key to identifying and avoiding potential problems around data diversification. This requires an understanding of the concerns of underserved individuals and communities regarding exploitation and stigmatisation, as well as issues of data ownership and sovereignty. Without attention to group as well as individual concerns, participant engagement may become tokenistic which in turn risks exacerbating existing, as well as creating new, inequalities.

3. It is crucial to contextualise these efforts within wider structural issues 

There are wider structural issues that influence researchers’ and participants’ attempts to generate diverse data. For example, (a) some researchers view data as neutral, but this ignores the social construction of data and technologies, and their tendencies to reflect societal inequalities. (b). Efforts to diversify data should be contextualised within the historical trajectory of structural racism and legacies of colonialism. (c) Classification and categorisation of populations have political consequences and need to be closely interrogated.

4. Conclusion

The review concluded that it is important to move actions beyond the recruitment of individuals from under-represented groups as the endpoint. Having more diverse datasets is not inherently more ethical. This is because if the broader historical, political, legal or social factors that shape the environments of potential participants are ignored, the risk of existing inequities being exacerbated remains high. These were extensively detailed as well as key recommendations for the Diverse Data initiative as it embarked on an ambitious, but ethically complex path. 

These recommendations included:

• Positioning ethics at the forefront of research and through, but in doing so, ensuring that it is seen more than just gaining research or institutional review board approval;
• Co-design should be at the heart of these initiatives, with participants as active researchers and knowledge makers;
• Shifting the focus from diversifying data towards enabling diverse ways of knowledge making, which must be largely driven by enabling a research culture that incentivises diversity through all aspects of the research process
• And of course, a re-iteration that data diversification needs to consider  the broader socio-political context.

We will be working on publishing numerous outputs spawned from this work over the coming year, including research papers that deep-dive into specific themes, as well as the publication of a roadmap for the practical implementation of ethics in data diversity activities so that initiatives, just like Diverse Data at Genomics England, can have a blue-print of what good practice might look like for us all to aim for. In addition this work has already helped the Diverse Data develop an ethics agenda and roadmap for the initiative, guide the design of future ethics work, and shape design elements of the programme.

Full report here.

If you’re interested in collaborating, or want to see early drafts of this emerging work, don’t hesitate to get in touch at diversedata@genomicsengland.co.uk and cpm@well.ox.ac.uk.

Announcing the winner of the CPM – St Anne’s Doodle competition

The Centre for Personalised Medicine recently ran a competition asking people who work or study at St Anne’s to send in sketches and paintings around a theme of ‘healthcare data’. We wrote about it in a previous blog post.

We’re delighted to announce the winning entry – these stunning paintings by Psychology and Philosophy undergraduate student Jake Mainwaring.

Jake writes: These paintings raise the debate: in the case of personal data, should the subject have the right to cover up something beautiful/useful (the painting underneath) if that would have bad consequences (e.g. data collected for research/statistical purposes being erased)?

Jake’s paintings vividly convey key challenges with collecting and using healthcare data responsibly: how can the beauty, complexity and nuance inherent in original data be retained while respecting the wishes and preserving the confidentiality of the person to whom those data relate?

We hope you enjoy these thought-provoking paintings as much as we did. Look out for future entries from our schools art competition, opening later this year!

International Women’s Day 2022

Today, the 8th March 2022, is International Women’s Day. This day is used across the world to celebrate the cultural, political, and socioeconomic achievements of women. To mark the occasion, JRF Nicky Whiffin spoke to some of the incredibly inspiring women that work with the CPM, from members of the core CPM team to our fantastic external advisory board.

I feel very fortunate to be surrounded by fantastic female role models in the CPM. I asked six of these women three questions probing who inspires them, what they see as the key issues facing women in science today, and what advice they would give to their teenage selves. Whilst these women come from a range of backgrounds there are some strong parallels in their experiences and their advice.

Meet the incredible women 

Left to right, top to bottom in image above

• Professor Anneke Lucassen: Our wonderful director, Professor of Genomic Medicine and head of the Clinical Ethics and Law in Society (CELS) group at the Wellcome Centre for Human Genetics.
• Dr Frances Rawle: Member of the external advisor board and previously Director of Policy, Ethics and Governance at the Medical Research Council (MRC).
• Dr Katherine Wood: CPM Junior Research Fellow and postdoctoral researcher at the Weatherall Institute for Molecular Medicine (WIMM).
• Helen King: Chair of the CPM steering group and Principal of St Anne’s College, Oxford.
• Professor Cecilia Lindgren: Member of the CPM steering group, Professor of Genomic Endocrinology and Metabolism, and Director of the Big Data Institute (BDI).
• Catherine Lidbetter: Our amazing program coordinator who is responsible for the operational running and day-to-day development of the CPM.

 

Question 1: Do you have any awesome women role models? If so, who and why?

Role models have been hugely important in my own journey in science. “You can’t be what you can’t see” is the phrase often used to describe how we are much more likely to see ourselves in positions when we can relate to the people who are already there. Our six CPM women take their inspiration from women in all walks of life.

Frances “Having grown up in the 60s and early 70s seeing women of my mother’s generation either having a career or a family but not both, my role models were my female friends (in whatever profession) and colleagues who were managing to successfully balance building their careers at the same time as having young children.“

Helen “When I was a fairly junior police officer, women senior officers tended to come from the ‘formidable and intimidating leader’ mould. A fantastic woman Chief Inspector called Anne Pyke wasn’t like that. She was friendly, compassionate and fun, as well as being highly respected and professional. It was such a relief to see that I didn’t have to change who I was in order to be successful in my career.“

Cecilia “Growing into being a scientist Leena Peltonen, Unnur Thorsteeinsdottir and Nancy Cox were women I admired and looked up to a lot and still do admire massively (except Leena who has sadly passed).“

Anneke “My mother. She studied chemistry in the 1950s and published seminal papers in her field of surface chemistry over nearly 50 years. Many had her home address as affiliation since she declined posts in the UK when the salary offered was half that of my father’s who had the same experience. My mother’s indignance at this sex discrimination was embarrassing as a teenager, but inspired me as an adult.“

Katherine “Professor Anne Goriely – Anne is an absolutely awesome supervisor who champions women in science and does everything she can to support the women in her life. Anne is extraordinarily caring, compassionate and kind, and while never celebrating her own outstanding achievements, she celebrates every success of those that she mentors. Anne’s own journey, from a degree in engineering (agronomy) to a PhD studying the development of the nervous system in Drosophila, to now a professor in human genetics, has been anything but linear; she is an outstanding researcher and mentor alike.“

Catherine “I found Jenny Douglas of the Open University inspiring when we worked on the CPM healthcare disparities conference. She wears her scholarship lightly and is so thoughtful in her interdisciplinary approach to race, ethnicity, gender and health.“

Question 2: What do you think is the greatest challenge for women in science today? How do we combat it?

Whilst in some ways we have made a lot of progress in equality between men and women in science, there are still some really key hurdles that we need to come together to tackle. Culture, juggling childcare, and unconscious bias were common themes across the answers to this question.

Anneke “That women still often have to acquire male attributes to succeed. We combat it by recognising that success in science can have many different forms. Appreciate teamwork: endorse we, not me, culture. Make science careers look attractive to early career researcher women and open to diverse personalities/attributes.“

Catherine “The greatest challenge I think (looking in) would still be the old chestnut of  juggling work with caring responsibilities, whether children or aged parents, or both, and life admin, etc.“

Frances “I think the greatest challenge for women, and indeed all early/mid career scientists, is to change the culture; to challenge discriminatory practices, to reduce the emphasis on the star players and increase the recognition of all those contributing to team science, to strive for and reward more effectively robust, reproducible science, to publish and value negative results. All this takes courage to risk the potential impact on your career of not playing by the established rules.“

Cecilia “I think (subconscious) bias against women manifesting itself in various ways is the biggest problem and we can combat this by raising awareness and discussing the issues often, offering external coaching mechanisms, and mentorship support (both peer mentorship and senior mentorship).“

Helen “I still think the greatest challenge for women is juggling, particularly if they have children or other caring responsibilities. Co-ordinating the instability, demands and opportunities of a research career, with the needs of others, perhaps including a partner’s career, whilst looking after your own mental and physical health, remains challenging and needs flexibility, creativity and compromise from all involved, including employers and group leaders.“

Katherine “I think one of the major issues we have is the problem of work-life balance and the difficulties of raising a family and being an academic. Taking a career break in the form of maternity leave to raise children inevitably leads to a “gap” in a woman’s CV without publications, where to the outside observer it appears that she was less productive. Once a woman has returned to work, managing the often long hours of research time, grant writing, paper writing, teaching etc can be extremely challenging and is often incompatible with raising small children. Coupled with the extremely high costs of childcare (even university-subsidised nursery places) compared to the average salary of a postdoc in the UK, it can make it very difficult for a woman to return to full-time research. We need to do more to support women who want an academic career and a family. The result of the leaky system also means there are simply fewer female role models in STEM subjects for the next generation to look up. If we want to encourage young girls to consider scientific careers, we need to ensure they have lots of awesome female scientists to be inspired by.“

Question 3: What advice would you give to your younger self?

Finally, I asked our six women what advice they would give to themselves as they were just finishing up school or starting university. The overwhelming theme running through these is to have more confidence in yourself and your abilities. So many women struggle with self-doubt. We can and should do more to build each other up and to tackle these insecurities in young women. 

Katherine “This one is simple! You CAN do it! There were so many times I doubted myself, or nearly didn’t apply for things because I thought my chances of success were very low. But unless you try, you will never know what your potential is! Better try and not succeed than don’t try at all!“

Helen “Probably to enjoy each current stage of your life a bit more, and worry about the future a little less!“

Cecilia “You are the best version of You there is and ever will be  – work on being authentically You and comfortable with that. I have struggled with imposter syndrome a lot (and still do at times), and coaching has helped me in finding my own voice and being calmly and kindly assertive, which feels amazing.“

Catherine “My advice to myself would be to trust my innate abilities, the ones I take for granted. Oh, and not to be too narrow in work focus.“

Anneke “Stop with the self doubt! Enjoy the career ride, see- rather than worry- where it takes you, meanderings and detours don’t matter, they enrich the end product.“

Frances “Have more confidence in your abilities. Find some good mentors.“

Thank you very much to all of the women across the CPM. You are all inspirational. And for anyone reading this, remember to believe in yourself. You have totally got this!

CPM – St Anne’s Doodle Competition

Blog post written (and doodles drawn) by Centre for Personalised Medicine Junior Research Fellow Rachel Horton

The Centre for Personalised Medicine is currently running a doodle competition for people at St Anne’s. (If you work or study at St Anne’s and you’re reading this before 28th February 2022, you’ve still got time to enter!)

The theme for the competition is ‘healthcare data’, and I’m really looking forward to seeing what people create, both because I’m sure it will help my own ideas around what healthcare data are and the interesting issues around them, but also because it’s a forerunner for a schools competition that I’m very excited about.

That said, ‘healthcare data’ in some ways feels like an inaccessible topic so I’m a bit nervous that people won’t see this as relevant to them. But the collection and use of healthcare data impact on everyone. We need data to understand and explore ways to improve healthcare, and we also need to consider what it means to be contributing data to such projects. What are the benefits and what are the risks?

For starters, what actually are healthcare data? We’d probably all agree on some aspects, like if you have your blood pressure measured by your GP, the measurement counts as ‘healthcare data’. But how about the information your phone might record about how many steps you’ve done today? Or the time you googled ‘what does croup cough sound like’? Or the information your local supermarket might have about how often they restocked the paracetamol this year?

When thinking about the healthcare data doodle competition, I had a go at a few doodles to try to draw out some thoughts around ‘healthcare data’ some a bit facetious and some more serious:

It’s interesting how many questions come up as soon as you start thinking about healthcare data, but somehow as a topic it perhaps looks a bit dry and distant from day-to-day life. How can we involve everyone in the decisions that we need to make as a society about how we collect and use healthcare data? The team at Understanding Patient Data is doing a lot of work on this, and it’s also an issue we’re really interested in at the Centre for Personalised Medicine (see animation here exploring using hospital data to improve healthcare).

If you work or study at St Anne’s, please join in and draw some doodles for our competition! But whether you’re based at St Anne’s or not, we’d love to hear more about what you think around these issues – how can we show everyone that they have experiences with and opinions about healthcare data, and that as a society we have choices to make as to how healthcare data is thought of, collected and used?

Introducing the CPM ‘vlog’ series

Last week, we launched a new flash interview “vlog” series. In this blog post, our Junior Research Fellow Dr Katherine Wood discusses the aims of these interviews and some of the key insights she took away from making the videos.

In this series, I have interviewed a range of different people involved in personalised medicine in one way or another, discussing their careers and their views on precision medicine now and in the future. These interviews will be released on a weekly basis so keep an eye on the CPM website and our Twitter feed (@CPMOxford) to ensure you don’t miss them! 

I have interviewed people from Professor Andrew Wilkie, a consultant in clinical genetics; to Dr Patrick Short, the CEO of Sano Genetics; and Professor Nina Hallowell, a professor of social and ethical aspects of genomics, to name but a few of our excellent speakers. The interviews covered many aspects of personalised medicine, from routine genetic testing in the clinic, the differences between academia and industry, the ethical implications of precision medicine, the role of bioinformaticians within the framework of large-scale genomics, and personalised therapies and pharmacogenetics.

One of the key themes which stood out to me was the difference in view between clinicians and academic researchers on the utility of genomic testing. Both Professor Andrew Wilkie and Dr Ed Blair raised the point that, from the perspective of a doctor, medicine has always been personalised and one would expect that whenever one sees a clinician, the care and treatment should be tailored towards the individual. While both highlighted the utility of targeted genetic testing for specific cases, there was scepticism about the role of widespread genomic screening in the clinic. On the other hand, both Dr Alex Geary and Dr Jamie Ellingford (bioinformaticians) hailed the exciting implications for research of being able to access and analyse vast quantities of DNA sequencing data. One key area many interviewees highlighted as a potential challenge going forward was the ability to process all the data we are collecting; is there really any point having so much information if we can’t analyse it all? Another interesting point raised by both Professor Andrew Wilkie and Professor Nina Hallowell was whether we should be investing so much into the genomics revolution at the expense of other factors which contribute to ill health (such as poor living conditions) or which we can test for simply and cheaply in the clinic (e.g. blood pressure). Overall, perhaps the take home message is that personalised medicine has many things to offer but it will not be the solution to everything!

On a different track, both Professor William Newman and Dr Andrew Douglas discussed the amazing potential of utilising “omic” data to tailor treatments to an individual. Professor Newman told us about the PALOH (Pharmacogenetics to Avoid Loss of Hearing) trial, a rapid point-of-care genetic test for newborn infants to prevent antibiotic-related hearing loss, while Dr Douglas’ discussion on antisense oligonucleotide therapies and the incredible successes there have been in the field so far left no doubt over the potential impact that tailored treatments can have on the patients’ lives. Finally, a particularly interesting chat with Dr Patrick Short from Sano Genetics highlighted the role that industry can and will play as we go forward with the personalised medicine revolution, and the fluidity between academia and industry these days. His careers advice for PhD students and postdocs is certainly worth a listen!

I really hope that you enjoy watching the videos and these snippets of insight into personalised medicine from many different perspectives! I certainly learned a lot making them.

Watch the Flash Interview Series here.

In conversation with Dame Mary Archer – CPM Podcast: Meet the Advisory Board Episode 2

The centre of personalised medicine podcast is hosted by Jiyoon Lee, president of the Oxford personalized medicine society and Dr Anika Knuppel, JRF at CPM.

In the second podcast episode as part of our meet the advisory board series, we had the honour to talk to Dame Mary Archer, who started her career as a chemist with a focus on sustainable energy production and solar energy conversion, and taught and researched at Oxford and Cambridge. When Dame Mary Archer left academia, she held a number of appointments, among them chairing Cambridge University Hospitals National Health Service (NHS) Foundation Trust and is currently chairing the Science Museum group. In 2012 she was appointed Dame Commander of the British Empire for her services to the NHS.

In our conversation with Dame Mary Archer we talked about her most notable career move and her views on the NHS and the future of the NHS. How having a grounding in science can be a perk in other industries, although “less usefully, it makes you obsess about details” making decision making hard at times. We discussed the role of science museums and why she now has considerable knowledge about railways. Furthermore, as a St Anne’s alumni, Dame Mary Archer could tell us about the changes in the university experience since leaving St Anne’s in 1966.

Finally, we spoke about personalised medicine and how the discovery of DNA has shaped our expectations of medical science and health. Dame Mary Archer’s career and personal health experience has given her a unique insight into the role of personalised medicine in patient decision making. She notes “Personalised medicine is here to stay, it is a force for good, increasingly powerful and should be a part of the clinicians and patients armoury in all appropriate cases to weigh that information and evidence and the balance what is the best way forward for that individual patient.”

Listen here for the full interview.

Dr Stanley Ho Memorial Lecture – Professor Jennifer Doudna

On the 2nd March 2021, the Centre for Personalised medicine was honoured to host Professor Jennifer Doudna to deliver the annual Dr Stanley Ho memorial lecture. Professor Doudna is an outstanding biochemical scientist who was the recipient of the 2020 Nobel Prize in Chemistry in conjunction with Professor Emmanuelle Charpentier, for their discovery and development of CRISPR-Cas9 gene editing technology.

CRISPR has revolutionised our ability to edit the sequence of DNA, which has important applications for understanding genetics and huge promise for treating human genetic disease. In this fascinating and engaging talk, Professor Doudna introduced how CRISPR-Cas9 was discovered and harnessed, from its origin within a bacterial immune system to its translation to human medical research (along with many, many other fields).

CRISPR stands for ‘clusters of regularly interspaced short palindromic repeats’. In simpler terms, this means a CRISPR sequence is made of repeating sequences of nucleotides (the building blocks of DNA). These repeats are separated by ‘spacers’. Unlike the repeated blocks, these spacers are variable. In bacteria, the original home of CRISPR, these variable regions are made up of DNA sequences taken from a virus the bacteria has encountered before.

If the bacterium is attacked again by this virus, this CRISPR DNA is transcribed, and RNA is transcribed from the CRISPR region. The produced crRNA (CRISPR RNA) then guides a ‘cutting enzyme’, Cas9, to the foreign virus’ DNA, damaging it, and preventing the virus from causing harm. It’s a basic immune system, and one which is very effective.

One of the overwhelming advantages of CRISPR-Cas9 editing compared to other technologies is how easily specificity of the system (i.e. which specific DNA base it is targeted to) can be changed; simply by changing the provided guide RNA in the CRISPR system, the Cas9 enzyme’s target site can be easily switched. This high level of site specificity combined with the efficacy of CRISPR-Cas9 gene editing gives CRISPR technology a clear advantage compared to previous gene editing technologies.

However, being a novel technology, CRISPR is not without current limitation. Currently, while cleavage can occur with high specificity, there is no known biological agent capable of carrying out specific DNA single nucleotide substitutions which would be desirable to treat human diseases driven by single DNA base changes. Professor Doudna discussed exciting on-going work to investigate adaptation of mechanisms known to exist to edit RNA in bacteria.

Despite limitations, some very promising clinical translation has already taken place. For example, the New England Journal of Medicine [1] reported the findings from two patients with ß-thalassemia and sickle cell anaemia who both have been successfully treated through a CRISPR-Cas9 edited bone marrow transplant. However, further clinical use is hampered by significant limitations on cell-specific targeting. Currently, all CRISPR-Cas9 editing for human use must take place outside of the body, which can be invasive and result in significant side-effects when the cells are returned to the patient. Professor Doudna discussed some of the innovative approaches being taken in pre-clinical research to potentially target specific tissue systems within the body, including the extra challenge of targeting the central nervous system for potential treatment of neurodegenerative disease.

There is also the issue of cost of treatment. CRISPR-Cas9 therapy is not cheap, and treatment in the NEJM published trials costs around a million dollars a patient. There is naturally then, a financial as well as a scientific barrier to more widespread clinical implementation, and Professor Doudna discussed how part of her current work at the Innovative Genomics Institute (ICG) at the University of California, Berkeley and the University of California, San Francisco, is to increase both accessibility and affordability of CRISPR-Cas9 therapy.

It is fitting in the ongoing pandemic that Professor Doudna also discussed how the high sequence specificity of CRISPR is being developed for use in COVID-19 diagnostic testing, allowing for a much more rapid testing than PCR alternatives. The fluorescence emitted by a ‘positive’ test could potentially even be detected using a smartphone camera, according to research published in Cell using a CRISPR-Cas13a system (one of many alternative Cas enzymes being studied) [2]. As the pandemic continues, this has huge potential for the future of commonplace and convenient SARS-CoV2 testing.

Professor Doudna rounded off the talk with a Q&A session, with audience questions including those on risk of immunogenicity of human harnessing of a bacterial system, Professor Doudna’s own opinions on the biggest barriers to therapeutic implementation, and discussion of some of the ethical concerns of human gene editing, to name a few.

We would like to extend a huge thank you to Professor Doudna for a fantastic and engaging talk and discussion. We hope everyone who was able to attend the webinar at this heavily subscribed event is excited (if you weren’t already!) about the potential CRISPR technology holds for the future. The talk is available on the CPM YouTube channel and is a fascinating watch which we highly recommend checking out!

Written by Holly Eggington, Secretary of the Oxford University Personalised Medicine Society (OUPM) and DPhil student at St Anne’s College

1.        Frangoul, H. et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. N. Engl. J. Med. (2021). doi:10.1056/nejmoa2031054

2.        Fozouni, P. et al. Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy. Cell (2021). doi:10.1016/j.cell.2020.12.001

In conversation with Dr Magdalena Skipper – CPM Podcast: Meet the Advisory Board Episode 1

The centre of personalised medicine podcast is hosted by Jiyoon Lee, president of the Oxford personalized medicine society and Dr Anika Knuppel, JRF at CPM.

In the first podcast episode as part of our meet the advisory board series, we had the honour to talk to Dr Magdalena Skipper, geneticist and editor and chief of the journal Nature.

She has over 18 years of experience in science publishing and has made history as nature’s first female editing chief and first editor-in-chief from a life sciences background.

In our conversation with Magdalena we spoke about women in Science, the work as an editor and new possibilities for scientific publishing, reproducibility as well as personalised medicine research, a topic described by Magdalena as “close to my heart”. Importantly, she highlighted the role of diversity in this personalised medicine “as wonderful as it has been and as much progress as we have made – the field has by and large focused on a subset of the global population. There has been great predominance of research on individuals of European descent […] but this is a tremendous opportunity to collect the data but also engage those communities in the research that’s being done […]”.

You can listen here.

Debating data: a mini citizens’ jury during a perfect storm

Post written by Professor Nina Hallowell and used with permission.

Professor Nina Hallowell is a member of the Wellcome Centre for Ethics and Humanities in the Nuffield Department of Population Health at the University of Oxford, and a member of the Steering Committee for the Centre for Personalised Medicine at St Anne’s College Oxford. In this guest blog post, she writes about what she learned from holding a citizens’ jury to understand how people feel about the way different kinds of health data are used. 

Given the speed at which research on data-intensive technologies is advancing, it is important to regularly gauge people’sviews on the use of healthcare data. As a group of researchers who either use healthcare data in our research or are interested in publics’ views about this issue* we decided to run a citizens’ jury in early 2020.  

Our aim was to gain some understanding of what members of the public think about the use of different types of healthcare data (MRI images, digital images of pathology slides and genomic data, i.e. DNA sequences) in research. Specifically, we were interested in people’s views on the benefits and challenges of sharing these different data types, and the acceptability of sharing healthcare data with commercial companies. We also wanted to trial the citizens’ jury method of public deliberation. 

Citizens’ juries

Citizens’ juries involve members of the public who come together to hear expert evidence about a topic of interest, deliberate the issue, (hopefully) reach a consensus and deliver their verdict.  

So over the last couple of months of 2019 we advertised in local media for jurors to participate in the ‘Debating Data Citizens’ Jury’ in early 2020.  

Data access on trial

On February 15th 2020, with the COVID-19 pandemic reaching the UK and storm Desmond making landfall overnight, twenty people braved the elements to attend our citizens’ jury in Oxford Town Hall. The jury members heard evidence about data collection, data analysis and data access from a series of expert witnesses in the fields of digital pathology, MRI imaging, genomics research and bioethics. The jury was given the opportunity to cross examine the witnesses, and then broke off into smaller groups to discuss a number of questions, including:  

• In which ways are these different types of data similar/different and why? 
• What relevance do these types of data have for you?  
• What ways should these different types of data be used? 
• Should these different types of data have different ‘rules’ about how they’re used and shared? 
• Who should/should not be able to access your data? 

Finally, each group was asked to reach a verdict on data use in research by answering the following question: How should the different data types be used, who should they be used by and why?  

The verdicts 

The jurors returned a series of statements about data use and commercial involvement in research:  

• Genomic data is different from MRI and pathology image data. It is more personal (it can identify individuals), could be misused, and therefore deserves greater protection and oversight. 
• Patients should be able to control uses of their data and should give consent for use of their healthcare data in research. 
• Private companies should be allowed to access healthcare data as we need them for their technological expertise, but their research should be more closely monitored and subject to more stringent oversight than publicly funded research. 

In addition to finding out what the jurors thought about researchers using healthcare data we asked them to reflect on participating in this event. Most were very positive, and said they had learnt a lot about the use of different types of data in research and appreciated the fact that we were interested in hearing their views. One participant said they: “learned much more about underlying science” and “felt better able to take an informed view.”  

Not all were so happy though. Another participant said that they felt the information they received was biased in favour of the use of data for research (although we did instruct witnesses to be as neutral as possible). This juror also felt there was not enough focus upon wider discussions about the use of personal data by the state and the politics of the NHS.   

Going forward 

This was the first citizens’ jury the team had organised, so Debating Data was a learning exercise for us too. At the end of the day we were relieved it appeared to go so smoothly. We were grateful that so many people had attended, given the weather. We were also pleased to hear a number of participants say they felt the day had given them a good opportunity to air their views.  

We noted a number of improvements for implementation in future events, including: more targeted recruitment to get a more representative sample of jurors, allowing more time for the witnesses to give evidence, and for jurors to cross-examine, deliberate and reach their verdicts.  

What will we do next? As you may have spotted, one of the jury’s conclusions was that people should give consent for the use of data in research. There are many ways to give permission for the use of data, including: opt-in, opt-out, broad or narrow consent and dynamic consent, to name but a few.  As it stands, the National Data Opt-Out allows people to opt-out of having their confidential patient data being used in healthcare research and for planning services. But if people do not opt-out does this really mean they consent to their data being used?  This sounds like an important question for a citizens’ jury, and we have plans to explore this in the future.  

—

* Members of the Wellcome Centre for Ethics and Humanities and the Centre for Personalized Medicine developed the event and members of two of the AI Centres of Excelllence – NPIC and NCIMI – helped us to run the event on the day.

Revisiting 2021 Annual Lecture by Dr Adam Rutherford

On Friday 26th March 2021, the CPM welcomed geneticist, best-selling author, and broadcaster Dr Adam Rutherford to give our annual lecture, titled Race, Genomes & Data: The Bias Built into Science. If you missed this outstanding talk, you can still catch it on YouTube here.

In this blog, we revisit Adam’s lecture and discuss some of the key concepts.

Dr Rutherford introduced three fundamental topics for his talk: (1) data is not neutral, (2) science is always political, and (3) scientists lack the language necessary to approach some of these issues.

Human genetics is the study of similarities and differences between individuals, but differences are often not solely, or at all, driven by genetics. Consider, for example, differences in experiences of the COVID-19 pandemic. In many Western countries, the risk of death from COVID-19 was substantially higher for those from minority groups. 

For example, one of the first large-scale studies of risk factors associated with COVID-19 death that was undertaken in the first phase of the pandemic in 2020 found that, after adjustment for other factors, Black and South Asian people in England were almost 1.5 times more likely to die from COVID-19 than people of white ancestry  (hazard rate 1.48 (95% confidence interval: 1.29 – 1.69) and 1.45 (95% confidence interval:1.32 – 1.58) respectively) [1].

Most observers appreciate that these differential experiences of the pandemic are not likely to be driven by genetic differences alone and that socioeconomic factors play an important role. Indeed ethnicity is a social construct that is associated with countless factors that amplify, influence, mediate, or confound associations between health exposures and health outcomes. For example, there was a clear occupation-related gradient in death from COVID-19; London bus drivers, regardless of their ethnicity, experienced higher death rates from COVID-19 than did residents of London more generally [2].

What is much less widely appreciated is how challenging scientists find formulating and applying an appropriate vocabulary to understand differences associated with ethnicity. Dr Rutherford argued that race and ethnicity are both socially constructed concepts that exist because society enacts them. He noted that race, genetic population, ethnicity, geographic population and ancestry are often used interchangeably in everyday language. Despite this, there are no precise or widely accepted definitions or even conventions to express these concepts in science or medicine [3].

“There are no generally agreed norms of race language in science or medicine”

Differences in pigmentation associated with skin colour are often a tangible source of difference between people, and are a conventional basis on which “race” might be assigned to a particular person. However, there is little to no correlation between skin colour and the similarities and differences between people and wider populations. Moreover, genetic variants that influence skin pigmentation emerged hundreds of thousands of years before homo sapiens itself emerged as a distinct species. There is more genetic variation related to pigmentation within Africa than outside it. Racial groups, as traditionally conceived, do not correspond to inherited, biological sources of variation.

It remains the case, however, that experiences of COVID-19, social status, occupational achievement, and health outcomes differ in many societies by conventional classifications of ancestral background (even if misunderstood and misapplied). This clustering of resources and socioeconomic advantages reflects wider historical, political and economic processes.  

Dr Rutherford also emphasised the role of science, in particular the scientific study of genetics, in developing notions of “race” . Carl Linneaus, the Swedish botanist and father of modern taxonomy, was the first naturalist to classify humans in the animal kingdom. In 1735, the first edition of his Systema naturae included “man” in the class of Quadrupeds and the order Anthropomorpha, later changed to Mammals and Primate respectively.  Man was classified into four types according to geography: 

• Europaeus albus: European white
• Americanus rubescens: American reddish
• Asiaticus fuscus: Asian tawny
• Africanus niger: African black

In the tenth edition of Systema naturae, Linneaus further characterised these four principal types of man in five categories: skin colour, physical traits, behaviour, manner of clothing, and form of government.

Not coincidentally (Linneaus was born in Sweden and spent most of his life there), the traits assigned to Europeans painted a more flattering picture of appearance and behaviour than those assigned to others. Europeans were wise and inventive, Asiatics haughty and greedy, and Africanus sluggish and neglectful. Indeed, the widely used and apparently neutral term ‘Caucasian’ was originally used (by Blumenbach) to characterise Europeans as beautiful (and by implication, more beautiful than other races).   

Linneaus’ classification was arguably the origin of scientific racism, the expression of which did not escape some of the most eminent names in the history of biology and of genetics specifically. Thomas Huxley, Darwin’s “bulldog” and passionate defender of evolution and natural selection, attempted a classification of humanity in which he identified some ten or eleven “races” referencing skin colour and geographic distribution.

Huxley’s classification included distinctions of race based on skin colour within the continent of Africa, a very distant echo of which was felt in the extremely violent genocidal conflict in Rwanda between the Tutsi and Hutu groups in the 1990s. This distinction between these groups stemmed from the 1930s, when the Belgian colonial government classified the local population into three ethnic groups (majority Hutu, minority Tutsi and the small Twa group). The classification, as one might imagine, lacked any meaningful basis, notwithstanding the subsequent entrenching of inter-group differences by the mythologizing propaganda of colonial and proselytising Christian influences. Over one million people are estimated to have died in this conflict.

Darwin himself was reserved about contemporary efforts to identify what may be described as race. Noting in the Descent of Man (1871) “the greatest possible diversity” of whether there was a single race or many, he concluded “…that it is hardly possible to discover clear distinctive characters between them”. Darwin’s sober opinion was not to be last word in this field.

“If you teach or work in human genetics, the ocean from which human variation is drawn, you have little choice but to speak of race and the history of eugenics”

Many methods still used in genetics and indeed science more generally were motivated by an interest in eugenics. The legacy of some of these individuals has been both productive and pernicious. To this day, many buildings, statues and scientific achievement awards are named after these individuals. Dr Rutherford’s view is that “we should be able to have complex and nuanced views about people”.

Another key point that Dr Rutherford discussed is how “data is never neutral”. Every stage of experimental design, data collection, and data analysis are conceived by individuals who themselves are influenced by both implicit and explicit biases. Some of these biases may be structural biases in the way in which we do science that may have existed for centuries.

“Data is never neutral because it is curated, designed and harvested by humans”

Dr Rutherford’s talk began by noting the changing context surrounding genetics and debate on race. One is the wider political environment in which debates around “race” have, in some respects, grown more divisive. This has occurred despite (or perhaps in part because of) the tremendous growth of genetics as a scientific discipline. Efforts to reduce and redress the historical imbalances in society as well as in the practice of genetics were subsequently discussed in the CPM’s “Facing Disparities in Healthcare” online conference, which confirmed both the need for urgent attention to these issues, but also their complex and multi-faceted political nature.

References:

[1] https://www.nature.com/articles/s41586-020-2521-4

[2] https://www.instituteofhealthequity.org/resources-reports/london-bus-drivers-review/london-bus-driver-review-phase-2-report.pdf

[3] https://arxiv.org/ftp/arxiv/papers/2106/2106.10041.pdf