Red Pills
No, this isn’t some adolescence-related rant, I’m talking about choosing to learn things that you can’t un-learn, about making a decision that you may come to regret - but not knowing that until it’s too late.
Those who know my wife and me, and those who have read her blog about our son Obi, will be aware that we approach things very differently. By way of a quick recap, I take [what I feel is] a very logical and scientific approach to things, especially problems. If we encounter a problem in any aspect of life I want to understand it, break it down into logical chunks, then plan how to solve each chunk - resulting in series of logical actions I can take to solve the problem. Normal right? Not for everyone apparently. Some things - I am told - shouldn’t be thought of in this way and that you can’t necessarily apply the same methodology to e.g. your 6-year-old daughter throwing a tantrum because it’s time to turn off PJ Masks as you might to a piece of software code that isn’t working as it should. We will agree to disagree there, but this is where the pills come in... or don’t.
Since we started our “journey” [yuck] into parenting a child with an undiagnosed genetic condition there have been all manner of “problems” we have encountered. Some that I have been capable of applying my normal methodology to – how to secure a child who doesn’t have control of his body into a baby chair in a restaurant that doesn’t have any straps? Easy stuff as you know – simply grab that Velcro mattress carrier that came with your daughter’s bed and wrap it around the chair, the child and secure at the back. Making sure you pad the back with the soft side of the nappy bag for cushioning. But that’s just a bit of creative physics, that I can do. Sadly though, there have been many problems that I haven’t been able to solve by applying this totally normal and logical process. These are mostly problems having to do with genetics.
Genetics 101 from a proven non-doctor
Genetics is a very complicated and specialist area of healthcare. It’s understandable - the human genome is massive, containing 3.1 billion DNA bases. It is also organised into genes - each made up of specific DNA sequences that provide instructions for things like “regulating biological functions” - or helping the body decide when it’s time to heal a wound, or when to grow or which parts of the food to digest vs discard.
These genes are what genetics is all about – the study of what individual genes do and which combinations are responsible for human traits. Things like height, eye colour, etc. are all down to our genes. However, out of the 20,000 or so genes that have been identified, we only understand about half of those, leaving 10,000 or so with unknown “roles” in the body. And this is the job of the geneticist, to study the unknown genes and try to figure out what they do, what they are responsible for and what happens if they are “corrupted”.
Errors
The thing is that nature is messy, and every one of us has errors in our genetic code. There is no exact “copy paste”, and genetic interfering is still illegal in 2025, so this means that everyone’s genome includes some “errors”. But that’s not necessarily an issue – there is plenty of the DNA that is not used within “functional” genes – so “errors” here don’t affect functionality of a gene. And even within functional genes there could be an “error” in a position that doesn’t affect the overall output. Then there are the errors that do impact.
As you probably know there are a whole bunch of *known* genetic conditions that some people are born with, these conditions are common enough to be “known” because there have been so many with the same “errors” present in their DNA that a geneticist found the connection between a set of errors and gave it a name. These disorders can include things like Down Syndrome, Angelman Syndrome, Cystic Fibrosis but also things like Cancer, Arthritis and Alzheimer’s can also be influenced by genetics.
The thing is though, not all “errors” mean you will develop any of these conditions, it might just be that you are more susceptible that someone without the error. Anomalies in DNA are super complicated as I mentioned and there’s literally billions of data points that could be poured over for any single person. Which is why they don’t.
Templates
No, to save time there are “templates” for the most common conditions, and when someone has had their genome sequenced [as our son has] their DNA is compared to the templates to see if there are any matches e.g. if we imagine the DNA is an alphabet, if the DNA has errors with genes F, H and U that could match with the “template” for Down Syndrome whereas errors with genes A, K and J could match the “template” for Angelman Syndrome.
The good news is that there are a *lot* of these templates. They account for all known genetic conditions across the globe and if a person has their genome sequenced [something a doctor would suggest if they suspected there were a genetic issue] then the likelihood is that these templates would be able to pinpoint a “known” condition and that person would be diagnosed with a genetic condition. Now it’s obviously not great for someone to be diagnosed with a genetic condition, especially if that someone is your 2-year-old son, but what’s worse than a diagnosis is the lack of one.
The bad news
So, for all those rare individuals who have errors in their DNA that don’t match a template, they get the moniker of “undiagnosed genetic condition” which is super unhelpful because, what does that even mean? It’s bad enough as a parent to know that there is something wrong, but we don’t know what – which is what put me into quite the spiral in the early days as I was trying to force my logical methodology onto fixing this problem – and then there’s the how do you answer the question “what’s wrong with him?” no idea! Anyway – more on that from Jo’s blog, she is better at that stuff – the silver-lining to it all is that there “could” someday be a diagnosis.
This can most recently be evidenced by the 100,000-genomes project and the Generation Study, both where the DNA of children with rare, undiagnosed conditions were all taken and examined trying to find matches. Turned out there were quite a few – enough in the 100,000 genomes project to create a new condition – the ReNu Syndrome where parents of children who have the same symptoms have been connected and are able to share in a community that has gone through – or is going through the exact same thing with their child, something the common genetic disorders have already; support, a community and forum for everything they are going through, specific to the condition they are dealing with.
For the rest of us though - we wait. We wait for the next trial, or for a new symptom to reveal itself and we ask the NHS cap-in-hand if the new symptom is enough to run another panel to see if there is anything else to match against. Or we wait the arbitrary 2-year period between genetics appointments as this is deemed a wide enough window where new symptoms – or new genetic research – might provide the basis for more tests. We wait. Or do we?
Pills
I did promise a Matrix type decision point, right? Well, here it is. An AI system. For rare genetic disease diagnosis.
What do we know about the human genome? It’s a massive data set. What do we know about AI? It can rapidly sort through, digest and process massive data sets. And last year I found the AI system that was created by a medical university in Texas. It’s called MARRVEL and you can access it here: https://marrvel.org/
First you take your input – the patient’s VCF [their entire genome saved in a special file format], this is a standard format for genetic testing so e.g. I know the NHS has this file containing Obi’s genome. Then you add the current known symptoms – we have these as identified by the geneticist, neurologist, physio, occupational therapist, speech and language therapist, dietician, gastroenterologist, cardiologist and all the other -ologists we’ve been seeing on a regular basis for the past 4 years! Then you press “go” and the genome data and symptoms will be compared – template fashion – but this time against all the other patients within the dataset which has sources from across dozens of undiagnosed patient databases, and all by a machine in a lot shorter order than asking for a panel from the NHS.
The final bonus – you can run this on a local machine with the datasets downloaded so your patient data never leaves your computer. Per previous blogs on data privacy and local AI this sounds like a no-brainer, right?!
Blissful ignorance
I had thought it was obvious – we have a tool that can be used to help gather more information about Obi’s condition, which sure beats waiting around for the next check in with the health service only to be told “wait some more”. I sent off for the VCF file through the neurologist who has been by far the most helpful doctor we have seen during our son’s care.
Then I got a phone call where she explained that while yes, they would have the file and yes it could be requested, the request would probably be rejected. That in cases of patient’s genomes the NHS wants to keep hold of this data and are worried about people taking it “elsewhere” to receive “unverifiable” diagnosis and potentially open themselves up to issues of insurance in the future.
But, what? The NHS is worried I might get a second opinion and deems itself the definitive source of truth on all things genetics, but won’t get on board with newer technology that can process things more quickly? Sounds a bit rich to me. And then I had a... we’ll say “lively debate” with Jo about it, she – not a water carrier for the NHS at all – seemed to think that they had it right and that we don’t want to open this pandora’s box. That, with a system that might tell us our son is going to be more susceptible to cancer, or other “potential” fates we should be more careful about this decision, that knowing can itself be worse than living in ignorance, that something like a reduced life expectancy might be something better off not read.
And that’s where we sit. Me on the side of the red pill, for I have always maintained that whatever it is, if I *know* it’s coming or could be, I can prepare for it mentally, and when “it” happens the blow will be that bit less. Whereas Jo sits firmly on the blue pill side, enjoying that steak and wine, but in doing so she is affected a lot more by those unexpected blows.
I call it her rollercoaster, and that while she may enjoy the highs that bit higher, I know that by towing the middle line I get to avoid those dips that I’m not sure I want to entertain.
So, who’s right? Probably neither, but definitely not the NHS. There is a tool available, open-source and as of October last year that could be put to use within the NHS – keep those VCF files – to potentially help thousands of families dealing with the same nightmarish position. So, until they start running more regular panels, or – probably more easily - taking technology seriously, I’ll keep beating the drum.
