Professor Andrew Green
Consultant in Medical Genetics, Children’s Health Ireland at Crumlin and Temple Street, Professor of Medical Genetics, University College Dublin and Principal Investigator, Conway Institute University College Dublin, Dublin
Can a sample of a person’s DNA ever be truly anonymous? When someone gets a genetic result about a disease or lifelong condition, how does it affect their family, and future generations of that family? And what kinds of diagnoses and interventions will we be able to do in the future using a person’s DNA?
These are some of the knotty questions that face genetics researchers, ethics committees and the field of genomic medicine more generally, according to Professor Andrew Green, a consultant in Clinical Genetics at Children’s Health Ireland.
And in an ever-evolving field, he calls for more awareness, clear and tiered consent and more genetic counsellors, to ensure that patients are protected while research into future diagnoses and interventions can continue.
Your DNA can identify you
Anonymity is often an ethical cornerstone in clinical research and trials, where patients’ identities are protected and decoupled from their data. But can a sample of someone’s DNA truly be anonymised?
As we move towards more thorough sequences and analyses of DNA, anonymity becomes less absolute, according to Professor Green.
“If you know what you are doing, you can identify people within an anonymised pile of patient genomes,” he says.
“Using small amounts of a person’s genetic data, say from a genealogy site, one can query a database to see if that person’s genomic data is in the database.”
This is of particular concern where genomic data are put on publicly available servers, he notes, or where a commercial enterprise holds the data, so firewalls are important to protect the information.
It’s key, says Professor Green, that participants are clear on the details of specific and tiered consent, though he notes that there are challenges around knowing what can happen to a patient’s data.
He outlines a hypothetical example where a pharmaceutical company is involved in research on how genetic variants affect response to a drug, and understandably needs access to the genetic data.
“But the twist of that is that in doing these studies, the company will also have DNA samples and clinical information from a large number of people who have the condition [under study], and that can become a biobank that is held not by a public or academic institution, but by a private company, which is a resource in itself and it may have commercial value,” explains Professor Green. “Participants who are being asked to contribute may need to be aware of that.”
Clear consent for unclear outcomes
It is a core tenet of ethics that participants in a study understand clearly what they are consenting to, but rapid advances can make this less straightforward.
As our understanding of genetics and genomics deepens through research, a more complex picture is emerging of how genes are linked to disease, explains Professor Green, and as more variations come to light, the outcomes of genetic tests are not always clear.
The challenge is not the testing or the analysis, it is the interpretation,” he says. ‘‘Often it is hard both for clinicians and for families to understand the results.”
Add to that the risk of unexpected ‘incidental’ findings that crop up during the analysis, and the prospect of samples being used to purposefully hunt out ‘secondary’ findings about unrelated conditions, and the waters can quickly muddy.
Consent for the future
As well as signing up for current research, participants in research and trials are often asked to consent for their samples to be used in future, unspecified research, explains Professor Green, and companies [and participants] need to be clear about what the future research is, but with new technologies gathering pace, it’s also hard to know what the future may offer. It’s also important to know that blanket consent to unspecified future research is illegal under the Irish Health Research Regulations and is also unethical.
He cites examples such as RNA interference, which blocks information encoded by genes in cells, CAR-T where cells in a person’s immune system are treated to boost their immune response against diseases such as blood cancer and drugs that specifically target gene products.
In the latter case, where drugs target proteins produced by specific genes, we have already seen huge benefits for people living with cystic fibrosis.
“Ivocaftor is produced to treat cystic fibrosis – you take it as a tablet and it targets the protein produced by the cystic fibrosis gene, a salt chloride channel,” he explains. “It has made a huge impact on hospitalisations and quality of life.”
Professor Green has seen the positive effects first hand.
“There is a cystic fibrosis unit where I work in Crumlin, specifically for children with great infection control going on, it was built some time ago and it has been very effective, and for the first time ever those beds were not occupied by children with cystic fibrosis, there were no CF children in the hospital at all, because of this drug,” he says.
Research has also developed ways of editing the genome directly, in particular CRISPR-Cas-based methods, he adds, which are being used in trials for many disorders but they have brought fundamental ethical issues to the fore too.
Consenting for the family
Another consideration about a genetic test is that it may impact the future not only of the person whose DNA is being analysed but the futures of their relatives too, says Professor Green, and this needs to be taken into account.
“Genetic information is probably qualitatively different from other medical information,” he says.
“It has a deterministic [and predictive] nature, in the sense that knowing what genetic issues you may have to deal with based on genetic testing or clinical assessment tells you something not just about where you are at this moment in time, but also the future,” he says.
“[A genetic variant] is something can’t change, and it determines a lot about you. And genetic information has implications not just for you as a person but also for your relatives – your children, your brothers and sisters, your parents – what you find out about yourself may impact on them. And that is the huge difference from other medical information.”
More resources needed
Professor Green broadly welcomes the HSE’s 2023 update on national policy for consent in health and social care research, which states that consent must be informed, specific, tiered, freely given and with the right to withdraw.
He also welcomes the HSE’s distinction between research testing and diagnostic testing, and he stresses that research results should not be used clinically, but should be confirmed in a diagnostic lab – ideally on a different sample – before being used to make clinical decisions.
However, the complexity of genetic and genomic testing and their far-reaching implications mean that people and their families need more counselling about tests and their results, but Ireland’s hospitals are woefully under-resourced, explains Professor Green, who calls for more genetic counsellors to help people to make sense of genetic testing, results and options.
“We have about 15 genetic counsellors in Ireland, and we should have about 70,” he says.
This blog has been written on foot of one of a series of presentations given by subject matter experts at the National Office’s ‘Lunch & Learn’ series. This is a learning and educational programme for the National Research Ethics Committee (NREC) members and wider research ethics community in Ireland.