The beauty of Gene therapy

Many decades ago, as a mature A level student with lofty ambitions to become a doctor, I studied nucleic acids as a part of the biology curriculum. I was struck with a sense of mystery and wonder at the beauty of it all and even made my own model of the double helix of DNA on a bit of old drainpipe.

A recent example is an illness called hereditary angio-odema, a condition that I tested for on several occasions and diagnosed in one patient. This is due to the lack of a single protein called C1 Esterase which regulates our allergic reactions. Without this, the cells lining our blood vessels become abnormally leaky and leads to swelling, uncomfortable rashes, breathing difficulty and pain. It is a difficult condition to treat, changes lives for the worse and is frequently fatal. Really awful bad luck due to a small gene defect which sends sensitivity to allergens dangerously wild.

Its rather like an incorrect sentence inserted into an instruction manual. Imagine mending a car with the wrong spark plug, or a wheel on the wrong way round, or indeed, only three wheels!

Then along comes gene therapy. With a single iv infusion, this life changing condition can be cured and has been likened to a ‘medical magic wand’. So just how does it work?

It really is mind blowing! The gene editing package containing RNA, the correct DNA and molecular scissors is contained in lipid nanoparticles. These are injected into the bloodstream and taken up by the liver where the protein, coded for by the faulty DNA should be produced. This is achieved using CRISPR technology which was originally discovered in bacteria who use the tool to protect themselves against the genetic manipulation of invading viruses.

It’s a bit of a mouthful, but CRISPR stands for Clustered, Regularly Interspaced, Short, Palindromic Repeats. Basically, like a puncture repair kit containing the correct DNA sequence, with instructions and molecular tools to detect and repair the faulty gene.

The trial results of C1 Esterase deficiency are impressive. As reported in the Guardian:

“It’s transforming patients’ lives,” said Dr Padmalal Gurugama, a consultant in clinical immunology and allergy at Cambridge University hospital. “My patient was having attacks every three weeks and that gentleman has not had any attacks in the past 18 months. He is not taking any medications. That is amazing.”

In this trial, of the 9 patients treated all but one had no further attacks and the other who has a lower dose had only one mild attack.

Misery, disability and deaths can be avoided and those formerly affected can lead normal lives. I cannot help feeling that this is the apex of medicine and I hope it will be available for many other life altering conditions caused by single gene defects. Examples include Cystic Fibrosis, Huntington’s disease Haemophilia, Sickle cell disease and many others.

There will also be applications of different sorts of gene therapy, for instance, when cancer cells can be identified by the proteins they produce. One method is called CAR-T. Put simply, white blood cells called T cells for the patient which recognise the specific protein can be generated in the lab. When infused back into the patient they can destroy the cancer. Initial results for myeloma are encouraging though it needs more study to look at potential unintended consequences and off target effects. At the moment it is used for refractory leukaemia in children and some cases of lymphoma in adults. Its future looks promising.

This editing technology also has many other applications, including changing the characteristics of food. Instead of genetic manipulation involving selective reproduction of plants with desired traits taking centuries, desired traits can be created. This including disease resistance crops, mosquitos who cannot carry malaria and many other applications.

There of course many difficult issue involved in what is colloquially termed ‘interfering with nature’. Yet I am beginning to think that in a world in where humans alone have changed the climate, increased the acidity of the oceans, replaced wildlife with farm animals, illuminated the shaded side our our own planet, damaged the very atmosphere that we depend upon, created intelligence far greater than our own, fear of gene therapy as somehow disrupting the natural world is misplaced. There is almost no ‘natural’ world left.

I eventually made it into medicine and soon found myself a junior doctor on the paediatric wards. I remember well those lovely children with Cystic Fibrosis and their parents I cared for. This too is caused by a single gene defect leading to tough and shortened lives. Currently about 11,000 people live with this condition in the UK. Things for them have improved with better medicine, therapies and care, but to be able to, in effect cure them so they can lead normal lives would be a genuinely incredible, fantastic thing.

Part of my motivation for this positive story of course, is that that mRNA, gene therapy and genetic manipulation have almost become dirty words in Mainstream Social Media (MSM). The success of mRNA vaccines, which are certainly not ‘gene therapy’ has been manipulated, distorted and has left many millions misinformed in a new phenomenon of what I call reverse education or mind damage.

Of course there are wider fears of where technology is taking us, much of which I have felt myself. There are big problems with cost, (currently about £1m per dose), corporative control of genes and their products, the beady eye and deep pockets of military research institutions, and the inequitable availability, as seen with mRNA vaccines, to the wider world.

This is also a world of rampant misinformation which applies to gene technologies as much as anything else. The nonsensical, counter productive and harmful memes ( memes are elements of a culture or system of behaviour passed from one individual to another by imitation or other non-genetic means) packaged as a result of the pandemic and now believed by millions relating to mRNA vaccines shows how beneficial technologies can become tragically demonised. Scientists, health professionals, governments and regulators will have their hands full!

Despite this I am frankly in wonder at how things are moving forward, and how much good can be done. For many millions of unlucky patients this could represent a wonderful leap forward.