There can be few technologies in modern history that have travelled so quickly from scientific triumph to political tribalism as mRNA.
For one side of the Covid debate, the vaccines were among the greatest medical achievements of the century, compressing what had traditionally taken a decade into less than a year. For the other, they became a symbol of institutional overreach, pharmaceutical profiteering, hidden agendas and government coercion. Five years after the pandemic, neither side has shown much interest in conceding ground.
Meanwhile, mRNA research has marched on, well outside of the furnace of public attention.
On 19 August pharmaceutical company Moderna’s share price exploded after it reported positive Phase III results (with over 1,100 participants) for its mRNA-based personalised melanoma treatment, developed in association with Merck (the Moderna-designed mRNA ingredient has the typically unpronounceable pharmaceutical name intismeran).
The market response was, even by biotech standards, completely off the charts. On the day of the announcement Moderna closed up roughly 177 per cent at $174.38, adding some $45 billion of market value in a single session, on volume nearly nineteen times its three-month average.
Why? Because investors were repricing the company based on the promise that they had developed an entire health technology platform that might treat multiple forms of cancer. The successful Phase III trial for one melanoma treatment regime was merely the billboard for a more important story that spans multiple cancers (and beyond).
These results are an indicator that mRNA may well turn out to be a general-purpose biological programming language. The noisy arguments about the efficacy and politics of the Covid vaccine will soon be an artefact of a very strange time – the enthusiastic cheers for a possible cure for cancer will drown them out.
How does it work?
Unlike conventional vaccines, this is not intended to prevent disease in healthy people. It is a therapeutic vaccine, produced individually for each patient – this is an entirely different approach from that of one vaccine manufactured at scale and applied to millions. Surgeons first remove the melanoma. Scientists then sequence the tumour’s DNA, identifying mutations unique to that patient’s cancer. Algorithms select dozens of neoantigens (proteins that exist only on those malignant cells).
Bespoke mRNA strand
Those are encoded into a bespoke mRNA strand, unique to one human being, and injected into the body to teach the immune system what to hunt. In other words, the immune system is effectively handed a personalised “most wanted” poster. And was AI used? You bet, although Moderna has been cagey about the exact machine intelligence architecture that it brought to bear on the research and development.
Traditional pharmaceuticals are manufactured in factories that produce individual molecules. Each new medicine requires its own lengthy optimisation process. mRNA changes the equation. The platform begins to resemble software more than chemistry. Instead of designing thousands of different drugs from scratch, this approach is more like drawing a villain’s identikit for the body’s immune police force and allowing it to do what it does best.
The Covid vaccines provided the first embryonic proof that this technique worked. Critics questioned safety, durability, hidden agendas and policy implementation. Those arguments will continue for years. Yet none of them determines whether the underlying technology is useful for treating cancer, autoimmune disease or rare genetic disorders. Those questions can only be answered by clinical trials. And now we are there, about five years after the first Covid rollout.
The melanoma results represent the strongest evidence yet of an entirely new treatment landscape, which is now coming into focus. The most obvious next targets are cancers known to respond to immunotherapy. Moderna and Merck are already conducting studies in lung cancer, bladder cancer and kidney cancer, all of which have similar tumour personalities.
BioNTech, best known alongside Pfizer for its Covid vaccine, is pursuing much the same vision. Its pipeline spans colorectal cancer, ovarian cancer and several other solid tumours, again based on identifying patient-specific mutations before rapidly manufacturing customised treatments. Competition is occurring not over a single drug but over an entirely new therapeutic architecture.
Nor does cancer exhaust the possibilities.
Autoimmune disease may prove even more intriguing. Several companies are investigating whether carefully designed mRNA molecules can retrain the immune system rather than simply stimulating it. Instead of provoking an immune attack, future mRNA medicines may persuade the immune system to tolerate tissues that it currently mistakes for foreign. Diseases such as multiple sclerosis, rheumatoid arthritis and lupus therefore sit on the longer-term horizon, although these remain considerably earlier in development.
This breadth explains not only the market’s enthusiasm, but that of the entire pharmaceutical industry – the possibility that mRNA becomes a universal delivery mechanism for medicine itself.
Side effects?
The melanoma protocol, which might change, sees six months of injections every two weeks. Side effects? Early trial reporting looks a bit like the Covid vaccine – somewhere around 50 per cent reporting fatigue, a sore arm and a day of chills. If you are someone with untreatable melanoma, it is a small price to pay. It will be available end-2027 at the earliest – there are still regulatory and practical hurdles to clear – and this field does not rush.
The optimism nevertheless requires several caveats.
Every personalised cancer vaccine is effectively a bespoke product requiring tumour sequencing, algorithmic analysis and rapid production before treatment begins. The logistics resemble precision engineering rather than pharmaceutical mass production. There is little precedent for it in global health logistics.
Regulators must also become comfortable evaluating medicines that differ slightly for every patient while sharing the same manufacturing platform. Existing approval frameworks were designed for identical pills, not customised biological software.
Then there is this, and it explains why the trials have been aimed where they have; the treatment works by hunting for the genetic errors in tumour cells. That requires that there are errors to find. Melanoma and lung cancer, the result of decades of battering by sunlight and cigarette smoke, are riddled with them, which is precisely why they were chosen first. Other cancers – prostate, thyroid, most childhood tumours, many leukaemias – are genetically more camouflaged, offering too few distinguishing marks to build a target list from.
Others, pancreatic cancer among them, wall themselves off behind dense tissue that the immune system has difficulty penetrating. Brain cancers are protected by the blood-brain barrier. And there are cancers this treatment cannot reach for mundane reasons: if the disease is moving faster than the six weeks it takes to build the drug, the patient dies before treatment arrives (this is a treatment for cancers that have already been removed and might come back – not for cancers in full attack mode).
Resistant to grand theories
Finally, biology remains stubbornly resistant to grand theories. Oncology is littered with technologies that looked revolutionary in one cancer and disappointing in another. Success in melanoma does not guarantee similar outcomes elsewhere.
But even so, the platform underneath them has just produced the first Phase III evidence that a computer can read a tumour and write a drug for one person, and that looks like the beginning of a glorious new era in health, one scientists have dreamt about for decades. Given our recent experience with Covid, it would be nice to keep politics out of it this time.
Raymond McCauley of Singularity University once described mRNA vaccines as “the first battle in the last war against disease” (for those interested in a discussion around this, it is here around 1:54). During the Covid years, that sounded like the sort of irritating Silicon Valley hyperbole that accompanies every new platform technology.
The latest melanoma results suggest that the remark may turn out to be prophetic.
[Image: Raghavendra V. Konkathi on Unsplash]
The views of the writer are not necessarily the views of the Daily Friend or the IRR.
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