Sanaria Fathulla: How do you think 100,000 Genome Project will be implemented? Do you think there will be any restrictions?
Arijit Mukhopadhyay: The implementation will happen over a long period of time. I am not aware of the exact specifics since I am not involved in the project. If you find a variant from the sequence data, that is usually not enough. If you find a variant with a known mutation for a particular disease, you will be able to predict, with high accuracy, that the individual will have the disease in the future. However, you will not be able to tell how that person has inherited the disease unless you sequence the parents. Even if the disease is dominant or recessive, the parents (one or both) maybe completely unaffected. That is why when the 100,000-genome project has recruited individuals, they must take unaffected family members as well, because the ability of anybody to assign a variant with a pathology is crucially dependent on the relative comparison with the absence of the variant in unaffected members. Eventually, the goal is to be able to make genotype-to-phenotype correlation. Now to answer your question, is it fully integrated, I do not think so. It is a slow ongoing process, but it is happening as we speak. It is a five-year project where the sequencing project was completed but done at various times. Some genomes were sequenced in year one, and some in year five so discoveries form year one would have progressed further.
When a genetic counsellor counsels one of these patients, they will have the backstory and they will know the clinical diagnosis, they know the sample, they know the genome sequencing results so that is the way it is integrated. Further integration that goes beyond the NHS, which I hope will happen, is when the findings are published, and new mutations are included in the public databases, meaning that anyone will be able to query a particular gene on NCBI and check which other variants are disease-causing. This has not happened yet. However, not every genome from the 100,000 Genome project will have a conclusive answer, as they might have variants of unknown significance (VUS). Many variants will be catalogued as VUS, some of which will have functions assigned as more sequences are deposited in the public domain.
SF: What made you decide to contribute to the BSGM and why is it important?
AM: The official society that is tasked with making these understandings available to the public and the ministry, and to the administrators, is called the British Society of Genomic Medicine (BSGM). I am a member of that society; it relates to what I do. They put out a call to all members more than five years ago when the UK had decided to be out of the European Union. At the same time, the new GDPR (General Data Protection Regulation) law was introduced by the EU, which UK had decided to follow. This understanding of that legal/political scenario is important because a question came from this. If the 100,000 Genomes Project is happening today and tomorrow, the long-time result is that everyone might have their genome sequenced at some point in time, what about the privacy of that data? The previous policy was not fit for purpose. That is why the document was made. I was interested because of how society changes with technological development and now you are hearing about AI, Chat GPT. Because this was right in my domain of expertise, I wanted to be part of that narrative. Having said that I was part of the subcommittee so if you see the document, you will see my name in the acknowledgements. My contribution was looking at the technical accuracy of the genetic sequencing bit of that documentation and correcting a few things in that draft. It was quite humbling going through this process of everybody’s contribution. My contribution was important, but small.
Updating such documents is important because Parliament is representative of the public. The NHS has faced multiple legal cases and litigations from members of the public, suing for not having the information they think they deserved due to lack of understanding. Parliament is final policy makers or approvers of new guidelines but lacks technical knowledge in the areas that are everchanging and need updating. That is why if it is a significant change that is happening in any area that is going to impact a larger portion of the public life, informing parliament is vital.
SF: Do you think the parliament should be able to have more say in genetics and its implications? Is there any right answer?
AM: Currently, the parliament should have a say but that is not specific to genetics. As I was saying, they are the policy approvers so they also have a say in any change in broader policies so GDPR, change in healthcare, how much of genomics will come into the forefront of healthcare all that will be governed by the parliamentarians so yes, they should have a say. We, as domain experts, through societies such as BSGM must be responsible for giving the right information to the parliamentarians.
SF: Who should have access to that data?
AM: The basic principle is that any personal information, you should be the decider of who should be able to get it. Having said that, it is actually a can of worms. In a sense, let us say, you are getting your genome sequencing done and there is a variant that puts you at a high risk of a certain disease when you are 50 years old. You chose not to reveal that to anyone, then when you are 50 years old, and if you have that disease and are unable to do your job. Your employers would need to support your wellbeing, but the work is suffering. So, what is the right answer? Especially if it is a private health insurance, or if it is your employers, should they have known before they employed you?
SF: What are the main problems in terms of consent and confidentiality hindering progress in making genetics a wide stream concept in healthcare/public?
AM: A General understanding and awareness about the pros and cons. What genetic info can tell and what it cannot tell. That’s the biggest thing lacking which you asked me earlier why I’m interested in engaging in such conversations, whether it’s part of my role in the subcommittee or in conversations like this, it’s part of that process I feel responsible that I should be engaging in any way to increase understanding and awareness of this. Until we have a general understanding of genetic data and what it means, we cannot have this public debate of who should have access.
SF: Do you think the public mindset on consent/confidentiality will change in the future?
AM: Although they are public documents, members of the public will never find the document due to lack of publicity. They do not feature in the front page of the newspaper; it is not the mainstream public information. The world has changed forever post-pandemic, people have become more aware of biomedical research and its potential. The 100,000 Genome Project is a very visible project so in that respect, people are now familiar with the technologies of genetics, but it stops there.
It is difficult to say, it will depend on the individual. People who are more aware will be able to make an informed choice. People who are less aware will simply say no or yes without understanding or they will depend on somebody to make the choice. People are not sure or do not feel comfortable sharing any private information, not just genetic data, worried about it getting misused or abused. As the technological risk is increasing, the technological protection is also improving. It will be a lengthy process, but it largely depends on the individual’s ability to understand the risk and benefits and give an informed choice.
SF: In the future, how do you think genetics will be used?
AM: The NHS published a document in 2016, proposing that genomics will be the first layer of healthcare. If you think of the current healthcare process, when you have a problem, you contact your GP, and the GP prescribes tests and medicine. At the very end, they can prescribe a genetic test as a last resort because it is expensive and complicated, it is not something you can buy a medicine with prescription and then feel better. The new genome generation is a future looking document proposing that a newborn baby will have their genome sequenced and any health condition that arises in their life will be seen as the first layer of information. The 100,000 Genome website today has100,000 newborn genome sequencing programmes. It is already in the process, and I think genomics will become the first step in public health soon.
SF: How do you think the NHS/government will be monitoring the data locally and internationally?
AM: It boils down to whoever pays to generate the data and receives the custody of the data. It does not mean they are free to share, but they have access to the data. Because the 100,000 Genome project is funded by the NHS, they are the custodian of the data but that does not mean NHS will be able to hold onto it forever. How it should be monitored depends on the funders, but a larger dialogue surrounds human genome sequence, because it is a naturally occurring phenomenon and it cannot be patented. NHS cannot monetise it therefore NHS will not be able to sell it to a third party or ask for something in return because it cannot be patented or monetised. Every big pharma company like GSK and Johnson & Johnson hold onto thousands of genome sequencing data of their own. They cannot monetise the data, but they can make profit off making drugs because they are a private company. The NHS cannot do the same, the indirect profit will be that public health will be improved. How it will be monitored is a complicated question to answer. I think large bodies such as the NHS, NIH, US, EU health care services, key representations from other nations must come together and form data policies so that most of this data is used for the greater good. Policy making is not my expertise, so I cannot say, I can only say it should be used for greater good.