We can do better

Abstract

The pandemic is over, thanks in part to rapid development of vaccines. Why then does it take so long to develop therapies for other major diseases?

In 2021, the world held its breath and waited for the magic potion that would finally put an end to the COVID pandemic. Suddenly, research was not an extra in life; it took centre stage for many people around the globe. What happened was fantastic. Several vaccine candidates based on different approaches and technologies sprinted through clinical trials to the finishing line and to the people. It all fell into place so fast that some worried whether corners had been cut and safety put at risk. The efficacy in ending the pandemic and the low incidence of side effects so far—shown in a recent retrospective study (Ashmawy et al, ²⁰²²)—confirm that FDA and EMA made the right call. The success of the COVID vaccine required essential factors: significant investment, teamwork, sharing of data, a sense of urgency, a well‐defined goal, responsive regulatory agencies and bringing together skills, knowledge and technologies developed over decades.

Thanks to the vaccines, the pandemic is finally over. The research teams have been applauded. The shareholders have had their reward. The awareness of research has risen. The citizens of the world know that scientists are able to deliver therapies to fight new diseases. And now they ask: why cannot we have therapies against other diseases? Each year, flu causes 650,000 deaths. TB causes 1.5 million deaths annually. Malaria and HIV/AIDS remain major scourges of the global South (https://ourworldindata.org/). But the interest to develop therapies stalled decades ago when the frontier moved to first world health challenges such as cancer. Funding work on a disease in a distant country does not pass the invisible national‐interest test, and meagre returns on investment would not excite shareholders and pharma managers.

Closer to home are the major health burdens, notably cancer (10 million deaths annually) and cardiovascular disease (18 million deaths). Almost everybody knows someone who has been affected. Not surprisingly, funding agencies and charities support research to address these major killers with enormous amounts of money. The output is huge: a PubMed search yields more than a quarter of a million publications related to cancer during the past year and half that large number on cardiovascular disease. However, there is no sign of COVID‐like progress other than incremental survival improvements for some cancers. Even despite occasional spurts, for instance, the immunotherapies to treat melanomas, most of the promises made in grant applications remain that: promises.

It is not that the research is poor or irrelevant. In just one random week, I saw the discovery that a potassium channel is a crucial pacemaker and implied in brain cancer. Another paper described the development of a drug targeted at the heretofore undruggable KRAS, which is implicated in 3% of colorectal cancers. A new method was developed to predict side effects that negated immunotherapies. Cancer vaccines based on the RNA technology that was the game changer for COVID are now in clinical trials. The flame of hope shines bright. But converting hope into delivery is the biggest challenge that has not been overcome.

Given the shining example of COVID vaccines, it is worth asking why progress on chronic diseases moves at glacial speeds. One reason is that the biology of these diseases is much more complex, individual susceptibilities vary and the disease category “cancer” needs to be subdivided into cell‐type‐specific diseases. But society demands more than scientific explanations of why it is so complicated. They see the latest “breakthrough” announcements of university PR departments. They are told that a newly funded project could finally deliver a new cure. The fact that it will take almost two decades before that happens—if it does—is merely an awkward sentence in the last paragraph. It is like telling children on a hike that “we are nearly there.” But the public has seen how fast science can move if needed and may become less tolerant for continuing excuses that “we are nearly there.”

It is time to discuss the reasons for the current inefficiencies in translating research into therapies and what consequences these may have on how we fund and organise research on major diseases.

First, researchers are obliged to over‐promise when they apply for funding. This hyperbole to pretend that every goose will lay a golden egg is well‐rehearsed by applicants and effectively promoted by granting agencies. Studies that try to understand the basic details of cell and molecular biology are an essential part of the research ecosystem, but basic research on its own is not enough to meet the health needs of the society that pays for it. The pathology and immunology associated with a pathogen like SARS‐Cov2 are also complex, and much of it are still not understood. But it was possible to quickly develop vaccines—and that is what the public has noted.

Second, the research enterprise is disorganised. It promotes and celebrates the individual's freedom to choose their topic of research. Those more than 250,000 pebbles of knowledge that are published each year are impressive, but they do not accrue quickly enough into a larger project with an explicit goal. If an industry was “in charge,” a number of changes would take place. Goals, milestones and timelines would be set. Topics would be prioritised. Some research groups would be redirected to training scientists while other groups would be given everything they need to super‐charge their activities. Links would be forged between groups that work on parts of the puzzle to achieve greater synergy for converting basic research into novel diagnostics and therapies.

Third, ethics review and control systems have become excessive in their zeal to avoid any risks. If we consider the example of genetic information and data sharing, we find a dichotomy between what society tolerates and what human ethics research committees (HRECs) permit. Millions of people have sent their DNA to companies offering them insights about their ancestry without any concerns about what happens to that information other than the report they receive. By way of contrast, an HREC will make it very difficult to use sequence data from a carefully designed study for future undefined studies even though these would have to pass HREC approval. Patients entering a hospital sign off, without much concern, a form to allow a clinician to perform diagnosis, treatment, surgery or biopsy. But a researcher at a different institution may not be allowed to access biological samples without engaging for months in complex legal negotiations—make those years when multiple institutions are involved. These opportunity costs are never considered. They would not have been tolerated if the material was needed to develop a cure for COVID. If the first RNA vaccine had been directed against cancer, it would have been delayed for years by HRECs as they pondered possible adverse events, whereas they were willing to reduce barriers for the COVID vaccines.

Finally, regulatory agencies have prioritised meticulousness over effectiveness. However, patients who have gone in vain through every available and debilitating treatment under “best practice” have literally nothing to lose. Giving them access to experimental treatments under carefully controlled schemes might benefit some patients and provide scientists with valuable data. At present, when a few have obtained the novel treatment through that humane loophole, an HREC or a regulatory agency will insist on a full‐scale clinical trial. Surely, there is a more compassionate way to help those who have exhausted every available treatment while simultaneously generating information about a promising new candidate therapy?

We have a vast amount of information, but it is generated in a random manner, and there is no obvious COVID‐like urgency to make sense of it and apply it in the clinic. In addition to asking for more urgency by regulatory agencies, two other possible solutions come to mind. An international organisation such as WHO could propose a goal or topic on which research in each country would focus during their next funding cycle. If, for example, ovarian cancer was selected and a global effort was undertaken to improve the outcomes of patients, the impact could be real and rapid. Another solution could be the equivalent of a Cochrane Review to clarify what progress is being made by researchers on a cancer‐by‐cancer basis, to highlight gaps that need to be filled and to establish better collaboration between research groups who have complementary parts of the puzzle.

Society saw the benefit of clearly defined goals and a single‐minded focus on finding a solution during the COVID pandemic. They could demand that the same mindset is applied to other diseases. Otherwise, appreciation for science will wane and research funding could be reduced in the wake of decreasing public support. If that happens, there will be no progress and patients will suffer as they do today.

Disclosure and competing interests statement

The author declares that he has no conflict of interest.