Earlier this year news broke about doctors in London curing blindness in children with a rare genetic condition.
The genetic condition was a severe, albeit rare, form of retinal dystrophy. It causes severe sight impairment and can be caused by defects in many different genes.
In this case, the four young patients had mutations in the gene encoding AIPL1. This accounts for up to 5% of infants affected by this condition, and has no treatment.
In this study, published in The Lancet, a team from the Moorfields Eye Hospital and University College London Institute of Ophthalmology injected a new copy of the gene AIPL1 into one eye of each patient to replace the defective one. The four children in the study showed improved functional vision without serious adverse effects.
The story of this incredible breakthrough actually begins 132 years ago. It highlights the importance of research done not for any clear application in the world – just curiosity. But around the world, this kind of research is under threat.
Understanding the world – just for the sake of it
Curiosity-driven research is exactly what it sounds like: research driven by the goal of understanding nature without regard for application. It has many aliases. “Blue-sky research”, “discovery science” and “basic science” are all terms commonly used to describe this approach.
This kind of research differs from “mission-directed research”, which focuses primarily on practical applications and whose goals are set by governments and industry.
The logic behind curiosity-driven research is that understanding how things work will inevitably lead to discoveries that will fuel innovation.
Historically, this has led to transformational discoveries. Another recent example is the 2023 Nobel Prize in Physiology or Medicine, which was awarded to Katalin Karikó and Drew Weissman for discoveries that enabled the development of effective mRNA vaccines against COVID.
The recent study in The Lancet follows more than a century of curiosity-driven discoveries culminating in these four children receiving their life-changing injections.
Sketching the structure of the retina
The kind of medical intervention used on these patients is called a gene therapy.
In this case, the cause of the condition is a defect in a single gene. This defect leads to the malfunction of an individual protein in the eye that is required for vision. The approach essentially is to provide a working copy of that gene to the eye, to restore function. This requires not only the technology to deliver the therapy, but the underlying knowledge of how AIPL1 functions in normal vision.
A sketch of several connected lines and circles.
In 1893, the pioneer of modern neuroscience Santiago Ramon y Cajal exquisitely sketched the structure of the retina. Santiago Ramon y Cajal/Wikipedia
This knowledge dates back to 1893, when the pioneer of modern neuroscience, Santiago Ramon y Cajal, exquisitely sketched the structure of the retina – the light-sensitive tissue at the back of the eye.
In the 132 years since, our knowledge of how this tissue converts light into an electrical signal for our brain to interpret as vision has significantly advanced. We now understand a lot about how this works.
This foundational knowledge also means we know precisely why a dysfunctional AIPL1 gene leads to severe vision impairment. It also enables us to predict that providing a working version could improve vision. Armed with this knowledge, we have an engineering problem. How do we get a working copy into the eye?
In this case, the working copy of AIPL1 was delivered by an adeno-associated virus, or AAV. These were first discovered in the mid-1960s, and without realising their therapeutic potential, several research groups dedicated themselves to understanding their biology.
An AAV was first used in a human patient in 1995 for the treatment of cystic fibrosis. Without this curiosity-driven research they would not have been developed into a gene therapy platform. This is how most modern therapies have emerged.
Woman with brown skin wearing a lab coat looking through a microscope.
Curiosity-driven research is driven by the goal of understanding nature without regard for application. Trust Katsande/Unsplash
Protecting curiosity-driven research
This is one of hundreds of therapies taking a similar approach. We will likely see many more stories like this in the coming decades. But I am certain we won’t see any examples where we don’t understand the underlying biology.
Curiosity-driven research, focused on understanding how biology works, is essential for the development of therapies to treat human disease. The history of medical advances shows us this time and time again.
Curiosity-driven breakthroughs include the discovery of X-rays as well as the antibiotic penicillin. The discovery of CRISPR/Cas9, an ancient bacterial defence, has enabled the editing of DNA with unprecedented precision. This has already led to an FDA-approved therapy to treat sickle cell disease.
Australia has punched above its weight in this arena for many years. But this is no longer the case.
Funding from the National Health and Medical Research Council, our largest funder of medical research, has been falling since 2020. More broadly, this coincides with a decline in the proportion of basic research being funded in Australia and directly threatens our capacity for curiosity-driven innovation.
Internationally, this strong focus on practical application is repeated. For example, 83% of the European Union’s €95.5 billion research funding program supports mission-directed research.
In Australia, and globally, we must protect curiosity-driven research at all costs and not underestimate the vital contribution it will make to our future.